1.
Expert Rev Anticancer Ther. 2020 Mar 20. doi: 10.1080/14737140.2020.1745634. [Epub ahead of print]
Melanoma immunotherapy: strategies to overcome pharmacological resistance.
Abstract
Introduction: Although checkpoint inhibitors have provided a breakthrough in how melanoma is treated, about half of patients still do not respond due to primary or acquired resistance. New strategies are, therefore, required to increase the number of patients benefiting from immunotherapy. This systematic review investigates novel combinations that may overcome immune resistance in patients with melanoma.Areas covered: We provide an overview of immune-related resistance mechanisms and the various therapeutic strategies that can be considered in attempting to overcome these barriers, including combined immunotherapy approaches and combinations with chemotherapy, radiotherapy, and targeted therapy.Expert opinion: The immune response is a dynamic process in which the tumour microenvironment and immune cells interact in a variety of ways. New treatment approaches aim to enrich the tumour microenvironment with immune-infiltrate and increase response to immune checkpoint inhibitors.
KEYWORDS:
combination treatment; immune resistance; immunotherapy; melanoma; tumour microenvironment
2.
Expert Rev Anticancer Ther. 2019 Dec;19(12):1089-1100. doi: 10.1080/14737140.2019.1703677. Epub 2019 Dec 17.
Surgical management of pancreatic neuroendocrine tumors: an introduction.
Hain E1,2, Sindayigaya R1, Fawaz J1, Gharios J1, Bouteloup G1, Soyer P3, Bertherat J4, Prat F2,5, Terris B2,6, Coriat R2,5, Gaujoux S1,2.
Abstract
Introduction: Neuroendocrine tumors of the pancreas (pNETs) represent only 1% to 2% of all pancreatic neoplasms. These tumors can be classified as functional or nonfunctional tumors; as sporadic or from a genetic origin; as neuroendocrine neoplasms or carcinoma. Over the last decade, diagnosis of pNETs has increased significantly mainly due to the widespread use of cross-sectional imaging. Those tumors are usually associated with a good prognosis. Surgery, the only curative option for those patients, should always be discussed, ideally in a multidisciplinary team setting.Areas covered: We discuss i), the preoperative management of pNETs and the importance of accurate diagnosis, localization, grading and staging with computed tomography, magnetic resonance imaging, endoscopic ultrasound, and nuclear medicine imaging; ii), surgical indications and iii), the surgical approach (standard pancreatectomy vs pancreatic-sparing surgery).Expert opinion: The treatment option of all patients presenting with pNETs should be discussed in a multidisciplinary team setting with surgeon's experienced in both pancreatic surgery and neuroendocrine tumor management. A complete preoperative imaging assessment - morphological and functional - must be performed. Surgery is usually recommended for functional pNETs, nonfunctional pNETs >2 cm (nf-pNETs) or for symptomatic nf-pNETs.
KEYWORDS:
Lymph node metastasis; Lymphadenectomy; Multidisciplinary team meeting; Pancreatectomy; Pancreatic neuroendocrine tumor; Pancreatic-sparing surgery
3.
Expert Rev Anticancer Ther. 2019 Dec;19(12):1061-1075. doi: 10.1080/14737140.2019.1699792. Epub 2019 Dec 6.
Interpretation of ceritinib clinical trial results and future combination therapy strategies for ALK-rearranged NSCLC.
Abstract
Introduction: Lung cancer is the leading cause of cancer-related deaths, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all lung cancer cases. The continued advancement of DNA sequencing technology and the discovery of multiple specific driver mutations underlying many cases of NSCLC are moving clinical intervention toward a more targeted approach. Here we focus on anaplastic lymphoma kinase (ALK), a member of the receptor tyrosine kinase family, as an oncogenic driver in NSCLC. The ALK gene is rearranged in 3-7% of NSCLCs, and targeted inhibition of ALK is a viable therapy option.Areas covered: We discuss the available treatment options for ALK-positive NSCLC with an emphasis on the second-generation ALK inhibitor ceritinib. We also discuss practical treatment strategies and possible strategies to overcome or delay resistance to ALK inhibitors.Expert opinion: With a robust treatment armamentarium for patients with ALK-positive NSCLC, emphasis has shifted to optimizing individualized treatment strategies to further enhance outcomes for these patients.
KEYWORDS:
ALK; ceritinib; non-small cell lung cancer; resistance
4.
Expert Rev Anticancer Ther. 2019 Dec;19(12):1009-1016. doi: 10.1080/14737140.2019.1699407. Epub 2019 Dec 3.
Durvalumab for the treatment of non-small cell lung cancer.
Abstract
Introduction: The prognosis of patients with advanced non-small cell lung cancer (NSCLC) remains poor, with a 5-year overall survival rate of around 15%. Immune checkpoint inhibitors, such as programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) inhibitors, have opened a new era in the management of NSCLC. Three checkpoint inhibitors (nivolumab, pembrolizumab, and atezolizumab) are currently approved by the US Food and Drug Administration (FDA) for advanced NSCLC. Durvalumab, an anti-PD-L1 antibody, is under investigation in several trials.Areas covered: This article reviews the pharmacological properties, clinical efficacy, and safety of durvalumab as monotherapy and in combination with other drugs for the treatment of locally advanced and advanced NSCLC.Expert opinion: Durvalumab as monotherapy or in combination with tremelimumab was effective with well-tolerated safety profiles for advanced NSCLC in several phase I or II studies. The PACIFIC study assessed the effectiveness of durvalumab as maintenance therapy following definitive chemoradiotherapy for unresectable stage III NSCLC, and met its primary endpoints of progression-free survival and overall survival. These results led to FDA approval for this NSCLC population. It will be exciting to follow ongoing phase III studies assessing how durvalumab fits into the rapidly evolving therapeutic landscape for advanced NSCLC.
KEYWORDS:
Durvalumab; NSCLC; PD-1; PD-L1; immune checkpoint inhibitors
5.
Expert Rev Anticancer Ther. 2019 Dec;19(12):1077-1088. doi: 10.1080/14737140.2019.1699065. Epub 2019 Dec 6.
The prognostic role of circulating tumor cells in colorectal cancer.
Abstract
Introduction: Metastasis is the main cause of cancer-associated death in colorectal cancer (CRC). The presence of circulating tumor cells (CTC) in the blood is associated with an increased risk of recurrence and poor prognosis. The clinical significance of CTCs as a novel biomarker has been extensively studied in the last decade. It has been shown that CTC detection applies to early cancer detection. The presence of CTCs is associated with metastatic spread and poor survival and is also useful as a marker for therapy response.Areas covered: We summarize the role of CTC in CRC, their clinical significance, current methods for CTC detection and challenges as well as future perspectives of CTC research.Expert commentary: The clinical significance of CTC in CRC patients is well established. Although insightful, the available marker-based approaches hampered our understanding of the CTCs and their biology, as such approaches do not take into account the heterogeneity of these cell populations. New technologies should expand the marker-based detection to multi biomarker-based approaches together with recent technological advances in microfluidics for single cell enrichment and analysis.
KEYWORDS:
CTC detection; Colorectal cancer; cancer progression; circulating tumor cells; disseminated tumor cells; metastasis
6.
Expert Rev Anticancer Ther. 2019 Dec;19(12):1005-1008. doi: 10.1080/14737140.2019.1699066. Epub 2019 Dec 2.
Hype or hope? The strange case of platinum salts' renaissance in breast cancer.
KEYWORDS:
BRCA1/2 mutation; Platinum salts; homologous recombination repair; triple-negative breast cancer
7.
Expert Rev Anticancer Ther. 2019 Dec;19(12):1051-1060. doi: 10.1080/14737140.2019.1698295. Epub 2019 Dec 6.
Advancements in the clinical management of upper tract urothelial carcinoma.
Abstract
Introduction: Upper tract urothelial carcinoma (UTUC) remains a complex disease to manage given challenges in staging, surgical resection, use of perioperative therapy, and prevention of bladder recurrences. High-level evidence is limited to guide management; however, recent data have shifted treatment paradigms. We intend to review recent evidence on advancements in the clinical management for UTUC.Areas covered: This review summarizes advancements in pre-operative work-up, surgical technique, and the use of intravesical and systemic therapy in both the neoadjuvant and adjuvant settings. Special comment is made on progress in the genomics of UTUC and how that can inform clinical practice.Expert opinion: Advancements in the clinical management of UTUC are most prominently being made in the neoadjuvant chemotherapy setting. Although level I evidence is sparse, data from both single and multi-institutional retrospective studies strongly encourage the use of neoadjuvant chemotherapy especially in high-risk or advanced-stage patients.
KEYWORDS:
Upper tract urothelial carcinoma; cancer care; immunotherapy; neoadjuvant chemotherapy; urologic advances
8.
Expert Rev Anticancer Ther. 2019 Dec;19(12):1001-1003. doi: 10.1080/14737140.2019.1696676. Epub 2019 Nov 29.
Why do the majority of patients not respond at all, or only partially or transiently, to immunotherapy?
KEYWORDS:
Immunotherapy; biomarkers; cancer vaccines; checkpoint inhibitors; oncology
9.
Expert Rev Anticancer Ther. 2019 Dec;19(12):1017-1027. doi: 10.1080/14737140.2019.1693270. Epub 2019 Nov 22.
Beyond immunohistochemistry and immunocytochemistry: a current perspective on galectin-3 and thyroid cancer.
Abstract
Introduction: Thyroid nodules are very common in the general population, most are benign, and do not require any intervention. However, often a challenge exists in discriminating benign thyroid nodules from cancer, without performing a biopsy or operation. Galectin-3 is a beta-galactoside binding protein that is involved in diverse biological processes and has been found to have increased expression in many human cancer types including thyroid cancer. As a result, recent studies have investigated its utility as a serum biomarker for thyroid cancer, as well as a novel target for in vivo molecular imaging of cancer. Additionally, given its role in tumorigenesis and cancer progression, galectin-3 targeting is currently under investigation for its potential utility as treatment for thyroid cancer.Areas covered: Recent studies of galectin-3 as a serum marker for thyroid cancer diagnosis, and in the preclinical setting as a target for cancer imaging and therapy.Expert opinion: Even though current studies evaluating galectin-3 as a serum marker and target for cancer imaging and therapy are promising, further research is required before it can be adopted into routine clinical use.
KEYWORDS:
FNA; Thyroid cancer; galectin-3; targeted therapy; thyroid cancer diagnostic imaging
10.
Expert Rev Anticancer Ther. 2019 Dec;19(12):1029-1050. doi: 10.1080/14737140.2019.1693893. Epub 2019 Nov 27.
Prognostic and predictive factors on overall survival and surgical outcomes in pancreatic neuroendocrine tumors: recent advances and controversies.
Abstract
Introduction: Recent advances in diagnostic modalities and therapeutic agents have raised the importance of prognostic factors in predicting overall survival, as well as predictive factors for surgical outcomes, in tailoring therapeutic strategies of patients with pancreatic neuroendocrine neoplasms (panNENs).Areas covered: Numerous recent studies of panNEN patients report the prognostic values of a number of clinically related factors (clinical, laboratory, imaging, treatment-related factors), pathological factors (histological, classification, grading) and molecular factors on long-term survival. In addition, an increasing number of studies showed the usefulness of various factors, specifically biomarkers and molecular makers, in predicting recurrence and mortality related to surgical treatment. Recent findings (from the last 3 years) in each of these areas, as well as recent controversies, are reviewed.Expert commentary: The clinical importance of prognostic and predictive factors for panNENs is markedly increased for both overall outcome and post resection, as a result of recent advances in all aspects of the diagnosis, management and treatment of panNENs. Despite the proven prognostic utility of routinely used tumor grading/classification and staging systems, further studies are required to establish these novel prognostic factors to support their routine clinical use.
KEYWORDS:
Pancreatic neuroendocrine neoplasms; biomarker; molecular marker; pathological factor; prognostic factor; surgical resection
- PMID:
- 31738624
- PMCID:
- PMC6923565
- [Available on 2020-12-01]
- DOI:
- 10.1080/14737140.2019.1693893
- [Indexed for MEDLINE]
11.
Expert Rev Anticancer Ther. 2019 Nov;19(11):993-999. doi: 10.1080/14737140.2019.1689820. Epub 2019 Nov 8.
The overall potential of CD47 in cancer immunotherapy: with a focus on gastrointestinal tumors.
Abstract
Introduction: CD47 is an anti-phagocytic ('don't eat me') signal overexpressed in many malignant diseases. It acts as myeloid immune checkpoint and thus has prognostic and therapeutic implications.Areas covered: This review presents and discusses the currently available data on the prognostic role and therapeutic value of CD47 in gastrointestinal tumors.Expert opinion: CD47 is overexpressed on the great majority of gastrointestinal tumors, cancer stem cells and circulating tumor cells. Overexpression of CD47 usually predicts a negative prognosis and seems to contribute to cancer immune evasion. The inhibition of CD47 has shown impressive results in clinical trials in hematologic malignancies. However, for gastrointestinal tumors only preclinical data is available. Inhibition of this myeloid immune checkpoint may yield great clinical benefit due to the abundance of myeloid effector cells. However, due to the ubiquitous expression of CD47 and the resulting antigen sink, vast amounts of antibody are required in order to reach therapeutic concentrations. QPCTL inhibitors blocking post-translational modification of CD47 protein may be a solution to this problem.
KEYWORDS:
CD47; Gastrointestinal cancer; SIRPα; checkpoint inhibition; colorectal cancer; don’t eat me signal; esophageal cancer; macrophages; pancreatic cancer
12.
Expert Rev Anticancer Ther. 2019 Nov;19(11):921-928. doi: 10.1080/14737140.2019.1685879. Epub 2019 Nov 4.
Elotuzumab in combination with pomalidomide and dexamethasone for the treatment of multiple myeloma.
Eleutherakis-Papaiakovou E1, Gavriatopoulou M1, Ntanasis-Stathopoulos I1, Kastritis E1, Terpos E1, Dimopoulos MA1.
Abstract
Introduction: Despite major advances in the therapeutic management of multiple myeloma (MM), it remains an incurable disease. Several combinations of monoclonal antibodies with novel agents are being investigated with promising results in order to prolong progression-free and overall survival.Areas covered: This paper aims to critically present available data from clinical trials investigating the combination of elotuzumab with pomalidomide and dexamethasone in refractory/relapsed MM patients and determine its current role in clinical practice.Expert opinion: Pomalidomide-based combinations with monoclonal antibodies have been shown to be effective in patients with MM who are refractory to or have relapsed following treatment with lenalidomide and/or a proteasome inhibitor (PI). These regimens seem to be more effective than the standard combination of pomalidomide with dexamethasone alone. Taking into consideration that the vast majority of MM patients will receive upfront treatment including a PI and lenalidomide in the near future, pomalidomide-based triplets, such as elotuzumab-pomalidomide-dexamethasone, will become the standard of care in the second line of therapy.
KEYWORDS:
Elotuzumab; immunomodulatory drugs; monoclonal antibody; multiple myeloma; pomalidomide; treatment
13.
Expert Rev Anticancer Ther. 2019 Nov;19(11):971-991. doi: 10.1080/14737140.2019.1686979. Epub 2019 Nov 13.
The landscape of tyrosine kinase inhibitors in sarcomas: looking beyond pazopanib.
Abstract
Introduction: Tyrosine kinases are key mediators of intracellular signaling cascades and aberrations in these proteins have been implicated in driving oncogenesis through the dysregulation of fundamental cellular processes including proliferation, migration, and apoptosis. As such, targeting these proteins with small molecule tyrosine kinase inhibitors (TKI) has led to significant advances in the treatment of a number of cancer types.Areas covered: Soft tissue sarcomas (STS) are a heterogeneous and challenging group of rare cancers to treat, but the approval of the TKI pazopanib for the treatment of advanced STS demonstrates that this class of drugs may have broad utility against a range of different sarcoma histological subtypes. Since the approval of pazopanib, a number of other TKIs have entered clinical trials to evaluate whether their activity in STS matches the promising results seen in other solid tumors. In this article, we review the emerging role of TKIs in the evolving landscape of sarcoma treatment.Expert opinion: As our biological understanding of response and resistance of STS to TKIs advances, we anticipate that patient management will move away from a 'one size fits all' paradigm toward personalized, multi-line, and patient-specific treatment regimens where patients are treated according to the underlying biology and genetics of their specific disease.
KEYWORDS:
biomarkers; kinases; sarcomas; signal transduction; targeted therapy; tyrosine kinase inhibitors
- PMID:
- 31665941
- PMCID:
- PMC6882314
- DOI:
- 10.1080/14737140.2019.1686979
- [Indexed for MEDLINE]
14.
Expert Rev Anticancer Ther. 2019 Nov;19(11):959-969. doi: 10.1080/14737140.2019.1686980. Epub 2019 Nov 5.
Stereotactic body radiotherapy in patients with multiple lung tumors: a focus on lung dosimetric constraints.
Abstract
Introduction: Lung dosimetric constraints with stereotactic body/ablative radiotherapy (SBRT/SABR) for multiple lung lesions are not well-characterized in published literature. Classically, the lung is considered a 'parallel' organ, for which injury to functional subunits could result in partially compromised function of that organ/tissue. Therefore, with SBRT/SABR for >1 thoracic target (especially involving both lungs), lung dosimetry requires special consideration.Areas covered: Current cooperative group and multi-institutional studies of SBRT/SABR for oligometastases rely on lung constraints from expert opinion, including constraints of exposure (i.e., volume of lung receiving more than a threshold dose or mean lung dose) and/or critical volume (i.e. volume of lung receiving less than a threshold dose; also termed complementary volume). For radiation pneumonitis, which reflects inflammatory lung injury, it remains unclear which type of constraint is more predictive of toxicity risks.Expert opinion: With SBRT/SABR for multiple lung lesions, it is prudent to use both exposure and critical volume constraints. Treatment on alternate days (for radiation plans with separate treatment fields) or staging treatment may also lower lung toxicity risks. Further study on lung normal tissue complication probability in the setting of multiple lung targets is urgently needed, particularly analyses of critical volume metrics, which are relatively poorly studied.
KEYWORDS:
SABR; SBRT; Stereotactic body radiotherapy; lung; oligometastases; pneumonitis; toxicity
15.
Expert Rev Anticancer Ther. 2019 Nov;19(11):939-945. doi: 10.1080/14737140.2019.1685877. Epub 2019 Nov 22.
Optimizing adjuvant therapies for the treatment of gastric cancer: with a special focus on Asia.
Sasako M1.
Abstract
Introduction: Today, there is a global consensus that adjuvant treatment is mandatory for stage II and III gastric cancer. What remains controversial, however, is what constitutes the best adjuvant therapy. A comprehensive review including published papers, doi documents, and abstracts from the ASCO annual meeting was undertaken to develop this updated review.Areas covered: Adjuvant treatments for stage II or more advanced and potentially curable gastric and gastroesophageal junction (GEJ) adenocarcinoma are, exclusively, reviewed and discussed.Expert opinion: The role of radiation is not yet established for gastric and GEJ cancers. Postoperative chemoradiotherapy offers no survival advantage over chemotherapy alone for patients who undergo D2 surgery. It is not yet clear if neoadjuvant chemoradiotherapy is better than adjuvant chemotherapy. Individualized treatment plans should be determined for many patients as efficacy depends on tumor histology, and toxicity varies enormously among effective options.
KEYWORDS:
Gastric cancer; adjuvant chemoradiotherapy; adjuvant chemotherapy; gastroesophageal junctional adenocarcinoma; multidisciplinary treatment
16.
Expert Rev Anticancer Ther. 2019 Nov;19(11):947-958. doi: 10.1080/14737140.2019.1685878. Epub 2019 Nov 14.
Minimally invasive surgery for pancreatic cancer.
Abstract
Introduction: Minimally invasive surgery (MIS) for pancreatic cancer has become very popular in modern pancreatic surgery. Evidence of the benefits of an MI approach are increasing thanks to prospective studies and randomized controlled studies.Areas covered: Agreement is lacking regarding the oncological feasibility of MIS for pancreatic cancer. Therefore, we performed a systematic review focusing on MIS for cancer of the head, body or tail of the pancreas. A total of 5237 studies were identified. After paper screening, 44 studies (22 on MI-pancreaticoduodenectomy and 22 on MI-distal pancreatectomy) met the eligibility criteria for the present review. The mean morbidity and mortality rates after MIPD were 31% and 4.9%, while overall complication and mortality rates were 32,5% and 1%. Median overall survival after MIPD and MIDP was 21.9 and 29.8 months, respectively. Both surgical and oncological outcomes were comparable to the open approach.Expert opinion: MIS offers advantages to the surgeon thanks to the high definition of the surgical field and the freedom of fine movement of the robot but should be considered only in selected patients and in high volume centers. Further studies are needed to prove the intraoperative and postoperative advantages of MIS compared to open surgery.
KEYWORDS:
Minimally invasive surgery; distal pancreatectomy; laparoscopic surgery; pancreas; pancreatoduodenectomy; robotic surgery; total pancreatectomy
17.
Expert Rev Anticancer Ther. 2019 Nov;19(11):929-938. doi: 10.1080/14737140.2019.1682554. Epub 2019 Oct 24.
Current status of biomarker testing in historically rare, high-unmet-need tumors: soft tissue sarcomas and thyroid cancers.
Abstract
Introduction: The development of precision medicine and targeted therapies have revolutionized cancer treatment. Historically, treatment was chosen based on the tumor-histology, but can now be tailored to patient-specific biomarkers. Investigations have shown up to 40% of cancer patients who undergo molecular testing have an actionable biomarker with a drug currently available, and that patients benefit from these drugs. In 2018, larotrectinib became the first drug developed and approved exclusively as a tumor-agnostic therapy. Because of advancement in precision medicine, biomarker testing has become a standard of care in a variety of tumors and its use is increasing.Areas covered: We discuss the landscape of biomarker testing in the context of soft tissue sarcomas and thyroid cancer, two rare diseases with historically high unmet needs in their subpopulations. We summarize historical data and contemporary applications.Expert opinion: The paradigm shift in oncology treatment toward precision medicine, including tumor-agnostic agents, is experiencing substantial momentum but still facing challenges. A gap exists between guideline recommendations for biomarker testing and clinical application, resulting in compromised access and suboptimal outcomes. Future progress will require routine access to testing and expanding treatment options coupled with awareness, predictability, and strategies to address resistance mechanisms.
KEYWORDS:
Biomarker testing; NTRK gene fusion; precision medicine; soft tissue sarcoma; thyroid cancer
18.
Expert Rev Anticancer Ther. 2019 Nov;19(11):917-919. doi: 10.1080/14737140.2019.1674651. Epub 2019 Oct 8.
Can CDK4/6 inhibitors cause fatal lung injury?
KEYWORDS:
Abemaciclib; Breast Cancer; Palbociclib; Pneumonitis; Toxicity
19.
Expert Rev Anticancer Ther. 2019 Aug;19(8):731-738. doi: 10.1080/14737140.2019.1654379. Epub 2019 Aug 19.
Immune checkpoint inhibitors: a new era for esophageal cancer.
Abstract
Introduction: The poor prognosis for patients with esophageal cancer (EC) requires evolving current treatment regimens. Immune checkpoint inhibitors show clinical efficacy and a great safety profile in multiple tumors. And the monoclonal antibodies that target programmed death receptor-1/programmed death receptor ligand-1 or the cytotoxic T lymphocyte antigen-4 pathway has shown potential curable effect of EC. Areas covered: This review article covers the prognostic significance of immune checkpoint expression, the accumulating current clinical studies of checkpoint inhibitors in esophageal cancer patients, and future directions. Expert opinion: Many clinical studies have reported favorable survival results with manageable toxicity of anti-programmed death receptor-1/programmed death receptor ligand-1 and anti-cytotoxic T lymphocyte antigen-4 treatment. More results are expected from future clinical studies. It is believed that combining chemoradiotherapy and immune checkpoint inhibitors can induce safe and efficient anti-tumor immune responses and can be a promising therapeutic strategy.
KEYWORDS:
Programmed death receptor-1; cytotoxic T lymphocyte antigen-4; esophagus cancer; immune; programmed death receptor ligand-1
20.
Expert Rev Anticancer Ther. 2019 Aug;19(8):717-729. doi: 10.1080/14737140.2019.1652095. Epub 2019 Aug 17.
Hedgehog pathway inhibition as a therapeutic target in acute myeloid leukemia.
Abstract
Introduction: The Hedgehog (HH) pathway constitutes a collection of signaling molecules which critically influence embryogenesis. In adults, however, the HH pathway remains integral to the proliferation, maintenance, and apoptosis of adult stem cells including hematopoietic stem cells. Areas covered: We discuss the current understanding of the HH pathway as it relates to normal hematopoiesis, the pathology of acute myeloid leukemia (AML), the rationale for and data from combination therapies including HH pathway inhibitors, and ultimately the prospects that might offer promise in targeting this pathway in AML. Expert opinion: Efforts to target the HH pathway have been focused on impeding this disposition and restoring chemosensitivity to conventional myeloid neoplasm therapies. The year 2018 saw the first approval of a HH pathway inhibitor (glasdegib) for AML, though for an older population and in combination with an uncommonly-used therapy. Several other clinical trials with agents targeting modulators of HH signaling in AML and MDS are underway. Further study and understanding of the interplay between the numerous aspects of HH signaling and how it relates to the augmented survival of AML will provide a more reliable substrate for therapeutic strategies in patients with this poor-risk disease.
KEYWORDS:
AML; Acute myeloid leukemia; Hedgehog; glasdegib; myeloid
21.
Expert Rev Anticancer Ther. 2019 Aug;19(8):655-657. doi: 10.1080/14737140.2019.1656398. Epub 2019 Aug 19.
What can we do to help young cancer survivors minimize financial hardship in the United States?
KEYWORDS:
Cancer survivorship; financial hardship; scholarships; young adult cancer survivors
22.
Expert Rev Anticancer Ther. 2019 Aug;19(8):673-679. doi: 10.1080/14737140.2019.1654378. Epub 2019 Aug 19.
Sacituzumab govitecan: breakthrough targeted therapy for triple-negative breast cancer.
Abstract
Introduction: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with an increased risk of recurrence and cancer-related death. Unlike hormone receptor-positive or HER2-positive breast cancers, there are limited targeted therapies available to treat TNBC and cytotoxic chemotherapy remains the mainstay of treatment. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate targeting Trop-2 expressing cells and selectively delivering SN-38, an active metabolite of irinotecan. Areas covered: This review covers the mechanism of action, safety and efficacy of sacituzumab govitecan in patients with previously treated, metastatic TNBC. Additionally, efficacy data in other epithelial malignancies is included based on a PubMed search for 'sacituzumab govitecan' and 'clinical trial'. Expert opinion: Sacituzumab govitecan has promising anti-cancer activity in patients with metastatic TNBC previously treated with at least two prior lines of systemic therapy based on a single arm Phase I/II clinical trial. A confirmatory Phase III randomized clinical trial is ongoing. Sacituzumab govitecan has a manageable side effect profile, with the most common adverse events being nausea, neutropenia, and diarrhea. The activity of sacituzumab govitecan likely extends beyond TNBC with promising early efficacy data in many other epithelial cancers, including hormone receptor-positive breast cancer.
KEYWORDS:
IMMU-132; Sacituzumab govitecan; Trop-2; antibody-drug conjugate; metastatic breast cancer; triple-negative breast cancer (TNBC)
23.
Expert Rev Anticancer Ther. 2019 Aug;19(8):689-696. doi: 10.1080/14737140.2019.1651648. Epub 2019 Aug 10.
Emotions in the room: common emotional reactions to discussions of poor prognosis and tools to address them.
Abstract
Introduction: Advanced cancer patients often want prognostic information, and discussions of prognosis have been shown to enhance patient understanding of their illness. Such discussions can lead to high-quality, value-consistent care at the end of life, yet they are also often emotionally challenging. Despite how common and normal it is for patients to experience transient emotional distress when receiving 'bad news' about prognosis, emotional responses have been under-addressed in existing literature on prognostic discussions. Areas covered: Drawing upon psychology research, principles of skilled clinical communication, and published approaches to discussions of serious illness, we summarize patients' common emotional reactions and coping strategies. We then provide suggestions for how to respond to them in clinic. Expert opinion: Ultimately, effective management of emotional reactions to bad news may lead to earlier, more frequent, and more transparent discussions of prognosis, thus promoting cancer patients' understanding of, and adjustment to, their illness and improving the quality of their end-of-life care.
KEYWORDS:
Advanced cancer; anxiety; communication; coping; oncologist; poor prognosis; psychological distress; sadness
- PMID:
- 31382794
- PMCID:
- PMC6709526
- [Available on 2020-08-10]
- DOI:
- 10.1080/14737140.2019.1651648
- [Indexed for MEDLINE]
24.
Expert Rev Anticancer Ther. 2019 Aug;19(8):659-671. doi: 10.1080/14737140.2019.1643239. Epub 2019 Aug 1.
Capmatinib for the treatment of non-small cell lung cancer.
Abstract
Introduction: Activation of the MET pathway through MET amplifications or mutations is present in 3-4% of stage IV non-squamous non-small cell lung cancers (NSCLC). High MET amplifications and exon 14 skipping mutations are associated with poor prognosis: new treatments are needed for these patients. Capmatinib is a highly selective, potent small-molecule MET inhibitor with antitumor activity in NSCLC in vitro and in vivo. Areas covered: This article provides an overview of the capmatinib clinical development program in NSCLC, both as monotherapy in NSCLC with a dysregulated MET pathway, and in combination with epidermal growth factor receptor (EGFR) inhibitor therapy in EGFR-mutant NSCLC with MET-based acquired resistance to previous EGFR inhibition. Expert opinion: In the GEOMETRY Mono-1 study, treatment with capmatinib resulted in high response rates in stage IV NSCLC with MET exon 14 skipping mutations, particularly in first line, supporting testing for this biomarker at the time of diagnosis. Durable responses have been reported and results in MET-amplified NSCLC are eagerly anticipated. In EGFR-mutant NSCLC, notable responses have been observed in combination with an EGFR-tyrosine kinase inhibitor (TKI) in case of acquired resistance to EGFR-TKIs based on high MET amplification.
KEYWORDS:
Capmatinib; MET inhibitor; NSCLC; non-small cell lung cancer; tyrosine kinase inhibitor
25.
Expert Rev Anticancer Ther. 2019 Aug;19(8):697-703. doi: 10.1080/14737140.2019.1643240. Epub 2019 Jul 18.
The use of alternative therapies in conjunction with opioids for cancer pain.
Abstract
Introduction: There is a growing recognition of the role of interventional techniques (IT) for the management of cancer pain (CP). However, there are many controversies on how and when to use such techniques. Areas covered: Patients who are unresponsive to systemic opioid analgesics or patients unable to tolerate systemic opioids may benefit from different IT for which the successful use depends on the selection of the right therapy for the right patient. The evidence regarding these techniques is often anecdotal and the potential risks, benefits, alternatives, and complications should be balanced to take a decision. Expert opinion: The successful use of IT depends on many factors, including a careful assessment of previous treatments, patient's characteristics, and the logistics. Risks, benefits, alternatives, and complications should be balanced to take a decision. Although IT have been described as effective in patients with CP, the evidence is still limited, unless for celiac plexus block, which has a high benefit-risk ratio. The intrathecal therapy should be chosen in patients who were poorly responding to opioid therapy, after an appropriate trial with different opioids. A careful selection of patients and techniques, a large experience in performing the procedures, sufficient logistics and staff skills, appropriate indications, and assessment of benefits and risks may help to achieve the best benefit for patients in individual cases.
KEYWORDS:
Cancer pain; intrathecal therapy; invasive procedures; neurolysis; sympathetic blocks
26.
Expert Rev Anticancer Ther. 2019 Aug;19(8):681-687. doi: 10.1080/14737140.2019.1642109. Epub 2019 Jul 15.
Exploring the link between diabetes and pancreatic cancer.
Abstract
Introduction: Epidemiological studies indicate an association between type 2 diabetes and pancreatic cancer but the complex and multidirectional relationship between them remains unclear. Areas covered: We summarized epidemiological evidence on diabetes and pancreatic cancer exploring the time-risk relationship. We described mechanisms linking long-standing diabetes to pancreatic cancer. We discussed pancreatic cancer-associated diabetes and its implication in the early detection of pancreatic cancer. Expert opinion: The markedly increased risk of pancreatic cancer in patients with new-onset diabetes compared with long-standing diabetes observed in several epidemiological studies indicates a complex and bidirectional connection, with long-standing diabetes being a predisposing factor for pancreatic cancer (increasing the risk of the malignancy 1.5- to 2-fold) and new-onset diabetes an early manifestation of the tumor. Identifying clinical features and biomarkers to distinguish pancreatic cancer-associated diabetes from type 2 diabetes is an important goal to improve management and survival of this cancer. Imaging (MRI) for middle-age patients with new-onset diabetes may be considered.
KEYWORDS:
Pancreatic cancer; review; type 2 diabetes; type 3c diabetes
27.
Expert Rev Anticancer Ther. 2019 Aug;19(8):705-716. doi: 10.1080/14737140.2019.1641086. Epub 2019 Jul 19.
A comparison of magnetic resonance imaging techniques used to secure biopsies in prostate cancer patients.
Abstract
Introduction: Prostate cancer (PCa) is the most common diagnosed malignancy among the male population in the United States. The incidence is increasing with an estimated amount of 175.000 cases in 2019. Areas covered: Primarily, PCa is generally detected by an elevated or rising serum prostate-specific antigen (PSA) and digital rectal examination (DRE) followed by pathological examination. Histopathology ultimately confirms the presence of PCa and determines a Gleason score. However, PSA and DRE have low specificity and sensitivity, respectively. Subsequently, accurate assessment of the aggressiveness of PCa is essential to prevent overdiagnosis and thus overtreatment of low-risk or indolent cancers. By visualizing PCa suspicious lesions and sampling them during the targeted biopsy, it is likely that the diagnostic accuracy of significant PCa improves. This article reviews the current imaging techniques used to secure biopsies in patients with a suspicion of PCa. The advantages and limitations of each technique are described. Expert opinion: Multiparametric magnetic resonance imaging (mpMRI) and subsequent-targeted biopsy have improved the diagnostic accuracy of PCa detection in men with an elevated or rising serum PSA. Prostate lesions visible on mpMRI are easily targeted during either in-bore MRI-guided biopsy, cognitive fusion biopsy or MRI-TRUS fusion biopsy.
KEYWORDS:
Biopsy; MRI-TRUS fusion; cognitive fusion; image fusion; magnetic resonance imaging; multiparametric MRI; prostate cancer; software fusion; systematic biopsy; transrectal ultrasound
28.
Expert Rev Anticancer Ther. 2019 Jul;19(7):569-587. doi: 10.1080/14737140.2019.1615889. Epub 2019 Jun 20.
Recent advances with cyclin-dependent kinase inhibitors: therapeutic agents for breast cancer and their role in immuno-oncology.
Abstract
Introduction: Collaborative interactions between several diverse biological processes govern the onset and progression of breast cancer. These processes include alterations in cellular metabolism, anti-tumor immune responses, DNA damage repair, proliferation, anti-apoptotic signals, autophagy, epithelial-mesenchymal transition, components of the non-coding genome or onco-mIRs, cancer stem cells and cellular invasiveness. The last two decades have revealed that each of these processes are also directly regulated by a component of the cell cycle apparatus, cyclin D1. Area covered: The current review is provided to update recent developments in the clinical application of cyclin/CDK inhibitors to breast cancer with a focus on the anti-tumor immune response. Expert opinion: The cyclin D1 gene encodes the regulatory subunit of a proline-directed serine-threonine kinase that phosphorylates several substrates. CDKs possess phosphorylation site selectivity, with the phosphate-acceptor residue preceding a proline. Several important proteins are substrates including all three retinoblastoma proteins, NRF1, GCN5, and FOXM1. Over 280 cyclin D3/CDK6 substrates have b\een identified. Given the diversity of substrates for cyclin/CDKs, and the altered thresholds for substrate phosphorylation that occurs during the cell cycle, it is exciting that small molecular inhibitors targeting cyclin D/CDK activity have encouraging results in specific tumors.
KEYWORDS:
Breast cancer; CDK inhibitors; chromosomal instability; clinical trial; cyclin D1
- PMID:
- 31219365
- PMCID:
- PMC6834352
- DOI:
- 10.1080/14737140.2019.1615889
- [Indexed for MEDLINE]
29.
Expert Rev Anticancer Ther. 2019 Jul;19(7):561-568. doi: 10.1080/14737140.2019.1631800. Epub 2019 Jun 25.
The role of combination chemo-immunotherapy in advanced non-small cell lung cancer.
Abstract
Introduction: Even with the currently recommended chemotherapeutic and immunotherapeutic treatment, the five year survival rate for advanced nonsquamous and squamous NSCLC without oncogenic drivers remains poor. However, several different chemo-immunotherapy combinations are presently being investigated - with favorable results- in order to increase the PFS and OS rates of these patients. Areas covered: Therefore, this paper aims to discuss the most promising trials investigating chemo-immunotherapy combinations and their present and future impact on advanced NSCLC treatment paradigms. Expert opinion: First line chemo-immunotherapy combinations are starting to and will certainly revolutionize the current paradigm of metastatic non small cell lung cancer treatment due to their superior performances - both in terms of PFS and OS - when compared to the actual standard of care platinum based chemotherapy. However, these associations are not devoid of problems, in fact, combining immunotherapy with chemotherapy obviously leads to enhanced treatment-related toxicities and to higher discontinuation rates; therefore these treatments should be administered carefully.
KEYWORDS:
Advanced NSCLC; atezolizumab; chemo-immunotherapy; chemo-immunotherapy combinations; chemotherapy; combination therapy; immunotherapy; nivolumab; pembrolizumab
30.
Expert Rev Anticancer Ther. 2019 Jul;19(7):589-601. doi: 10.1080/14737140.2019.1631162. Epub 2019 Jun 17.
Exploiting DNA repair defects in breast cancer: from chemotherapy to immunotherapy.
Abstract
Introduction: Impaired DNA damage response (DDR) and subsequent genomic instability are associated with the carcinogenic process itself, but it also results in sensitivity of tumor cells to certain drugs and can be exploited to treat cancer by inducing deadly mutations or mitotic catastrophe. Exploiting DDR defects in breast cancer cells has been one of the main strategies in both conventional chemotherapy, targeted therapies, or immunotherapies. Areas covered: In this review, the authors first discuss DDR mechanisms in healthy cells and DDR defects in breast cancer, then focus on current therapies and developments in the treatment of DDR-deficient breast cancer. Expert opinion: Among conventional chemotherapeutics, platinum-based regimens, in particular, seem to be effective in DDR-deficient patients. PARP inhibitors represent one of the successful models of translational research in this area and clinical data showed high efficacy and reasonable toxicity with these agents in patients with breast cancer and BRCA mutation. Recent studies have underlined that some subtypes of breast cancer are highly immunogenic. Promising activity has been shown with immunotherapeutic agents, particularly in DDR-deficient breast cancers. Chemotherapeutics, DNA-repair pathway inhibitors, and immunotherapies might result in further improved outcomes in certain subsets of patients with breast cancer and DDR.
KEYWORDS:
Breast cancer; DNA damage response; PARP inhibitor; immunotherapy
31.
Expert Rev Anticancer Ther. 2019 Jul;19(7):633-644. doi: 10.1080/14737140.2019.1626234. Epub 2019 Jun 21.
An update on advanced dual-energy CT for head and neck cancer imaging.
Abstract
Introduction: Dual-energy-computed tomography (DECT) is an advanced form of computed tomography (CT) that enables spectral tissue characterization beyond what is possible with conventional CT scans. DECT can improve non-invasive diagnostic evaluation of the neck, especially for the evaluation of head and neck cancer. Areas covered: This article is a review of current applications of DECT for the evaluation of head and neck cancer, focusing largely on squamous cell carcinoma (HNSCC). The article will begin with a brief overview of principles and different approaches for DECT scanning. This will be followed by a review of different DECT applications in diagnostic imaging and radiation oncology, practical and workflow considerations, and various emerging advanced applications for tumor analysis, including the use of DECT datasets for radiomics and machine learning applications. Expert opinion: Using a multi-parametric approach, different DECT reconstructions can be used to improve diagnostic evaluation and surveillance of head and neck cancer, including improving visibility of HNSCC, determination of tumor boundaries and extent, and invasion of critical organs such as the thyroid cartilage. In the future, the large amount of quantitative information on DECT scans may be leveraged for improving radiomic and machine learning models for tumor characterization.
KEYWORDS:
Dual energy CT; TNM; cervical lymph nodes; head and neck cancer; lymphadenopathy; spectral CT; squamous cell carcinoma; thyroid cartilage invasion
32.
Expert Rev Anticancer Ther. 2019 Jul;19(7):645-653. doi: 10.1080/14737140.2019.1626723. Epub 2019 Jul 12.
Value of quantitative and qualitative analyses of serum and urine cell-free DNA as diagnostic tools for bladder cancer: a meta-analysis.
Abstract
Background: Qualitative and quantitative analysis of circulating cell-free DNA (cfDNA) is a potential detection method for bladder cancer. Many studies have focused on the reliability of these results, but the conclusions have not been consistent. Methods: We performed a diagnostic meta-analysis to investigate the diagnostic significance of serum and urine cfDNAs with tumor tissues as the standard control. We searched the MEDLINE, EMABASE, and Cochrane Central Controlled Trials Register (CCTR) databases until January 2019. Results: A total of 11 studies involving early and/or advanced bladder cancer were finally included. The overall diagnostic accuracy was measured as follows: pooled sensitivity and specifcity were 0.69 (95%CI: 0.67, 0.71) and 0.72 (95%CI: 0.70, 0.74). Pooled positive likelihood ratio and negative likelihood ratio were 3.10 (95%CI: 2.35, 4.07) and 0.41 (95%CI: 0.34, 0.49). Combined diagnostic odds ratio was 8.26 (95%CI: 5.64, 12.11). A high diagnostic accuracy was demonstrated by the summary receiver operating characteristic curve, with area under the curve of 0.80 (95%CI: 0.77, 0.83). Conclusions: CfDNA assay has high diagnostic value for the detection of bladder cancer. Larger sample studies are needed to further confirm our conclusions and to make this approach more sensitive and specific.
KEYWORDS:
CfDNA; biomarkers; diagnosis; meta-analysis
33.
Expert Rev Anticancer Ther. 2019 Jul;19(7):543-545. doi: 10.1080/14737140.2019.1625773. Epub 2019 Jun 5.
Should chemotherapy still be used to treat all muscle invasive bladder cancer in the "era of immunotherapy"?
KEYWORDS:
Muscle invasive bladder cancer; chemotherapy; immunotherapy
34.
Expert Rev Anticancer Ther. 2019 Jul;19(7):613-631. doi: 10.1080/14737140.2019.1625774. Epub 2019 Jun 8.
Personalizing surgical margins in retroperitoneal sarcomas: an update.
Abstract
Introduction: Tumor biology, as well as completeness of surgical resection, are two important prognostic factors when treating retroperitoneal sarcoma (RPS). A frontline extended surgical approach is associated with improved local control and possibly improved survival. However, this approach has to be tailored to each histological subtype, as the patterns of growth and recurrence risks vary significantly among them. Areas covered: We provide a review of the literature in RPS, describing the behavior of each of the five main histologic subtypes: well-differentiated liposarcoma (WDLPS), dedifferentiated liposarcoma (DDLPS), leiomyosarcoma (LMS), solitary fibrous tumor (SFT) and malignant peripheral nerve sheath tumor (MPNST). The prognostic factors relevant to oncologic outcomes of RPS, the role of margins and the importance of local control are discussed. Finally, a histologic specific surgical approach to RPS is provided in detail. Expert opinion: While tumor-related factors are paramount, the only intervenable predictive factor is extent and quality of surgery. The extended surgical approach has been advocated for previously and again we describe it in more detail, tailored specifically to the tumor subtype. The aim of this approach is to maximize the possibility of achieving a complete resection through a standardized approach based on histologic behavior and site of origin.
KEYWORDS:
Leiomyosarcoma; extended resection; liposarcoma; malignant peripheral nerve sheath tumor; outcome; pelvic sarcoma; prognosis; retroperitoneal sarcoma; sarcoma; solitary fibrous tumor; surgery; surgical margins
35.
Expert Rev Anticancer Ther. 2019 Jul;19(7):603-611. doi: 10.1080/14737140.2019.1625772. Epub 2019 Jun 8.
The role of metastasectomy in advanced renal cell carcinoma.
Apollonio G1, Raimondi A1, Verzoni E1, Claps M1, Sepe P1, Pagani F1, Ratta R1, Montorsi F2, De Braud FGM1, Procopio G1.
Abstract
Introduction: So far, clinical experiences have proved metastasectomy as the only approach in the setting of metastatic renal cell carcinoma that may achieve the 'no evidence of disease' status, with an associated improvement in survival. Areas covered: This review aims to summarize the body of knowledge on therapeutic approaches to mRCC, with a specific insight on the role of metastasectomy and on which underlying factors could be good predictors to select patients who may benefit from surgery. In detail, we managed to identify as potential selection criteria: the number of lesions and their site, the DFI, patients' performance status and, most of all, the completeness of resection. Expert opinion: The definition of the optimal treatment strategy of mRCC patients is still an unmet clinical need. The decision-making process about treatment strategy should consider specific tumor's and patient's characteristics, as well as the integration of the available therapeutic approaches with the aim to reach the best clinical outcome. We consider multidisciplinary management mandatory in order to tailor the treatment approach according to the patient and disease features. The experience of clinicians may be considered crucial in order to select the best candidates for a multimodal approach.
KEYWORDS:
Metastasectomy; immunotherapy; renal cell carcinoma; surgical approach; targeted therapies
36.
Expert Rev Anticancer Ther. 2019 Jul;19(7):541-542. doi: 10.1080/14737140.2019.1626722. Epub 2019 Jun 5.
An aspirin a day keeps ovarian cancer at bay?
KEYWORDS:
Aspirin; ovarian cancer risk
- PMID:
- 31159617
- PMCID:
- PMC6650606
- [Available on 2020-07-01]
- DOI:
- 10.1080/14737140.2019.1626722
- [Indexed for MEDLINE]
37.
Expert Rev Anticancer Ther. 2019 Jul;19(7):547-559. doi: 10.1080/14737140.2019.1596030. Epub 2019 Jun 14.
Epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small cell lung cancer.
Abstract
Introduction: Epidermal growth factor receptor (EGFR) mutations are well-described drivers of non-small cell lung cancer (NSCLC) and EGFR tyrosine kinase inhibitors (TKIs) have become key components of the NSCLC front-line treatment landscape. Tumors inevitably develop resistance to these agents, and development efforts continue to focus on identifying mechanisms of resistance and drugs to target these mechanisms. Areas covered: With several EGFR TKIs approved for use in the first-line or in later-line settings, an understanding of the efficacy and safety of these inhibitors in various populations is warranted. Furthermore, given the frequent emergence of drug resistance in NSCLC, examination of tumor tissue throughout the disease course provides the opportunity to select treatments based on the tumor's mutation profile. Here, we discuss: key efficacy and safety findings for approved and investigational EGFR TKIs; known mechanisms of resistance, particularly the T790M acquired EGFR mutation; and recent advances in EGFR mutational testing that may facilitate less invasive tissue testing and guide treatment selection. Expert commentary: The expanding armamentarium of EGFR TKIs, improvements in the understanding of resistance mechanisms and technological developments in the molecular analysis of tumors may help render EGFR mutation-positive NSCLC a chronic disease in many patients by facilitating optimal sequential therapy.
KEYWORDS:
mutation; Drug resistance; investigational drugs; mutational testing; non-small cell lung cancer; treatment outcomes
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