1.
Expert Rev Anticancer Ther. 2020 Mar 12:1-7. doi: 10.1080/14737140.2020.1736566. [Epub ahead of print]
Further insights into testicular germ cell tumor oncogenesis: potential therapeutic targets.
Abstract
Introduction: Testicular germ cell tumors (TGCTs) are the most common neoplasia in the young male population, and the incidence has been constantly increasing in many parts of the world. These tumors are classified into seminomas and non-seminomas, and those divided, in turn, into yolk sac tumors, embryonal cell carcinomas, choriocarcinomas, and teratomas. Although therapeutic approaches have improved, approximately 25% of the patients relapse or, in a small number of cases, show platinum-resistant disease.Areas covered: We review several molecular targets that have recently emerged as powerful tools for both diagnosis and therapy of TGCTs. Moreover, we reviewed the most frequent deregulated pathways involved in TGCT tumorigenesis, reporting drugs that may emerge as novel therapeutic agents.Expert opinion: TGCT treatment is mainly based on platinum-derivative therapy with high cure rates. However, in the refractory patients, there are few alternative treatments. Thus, different pharmacological approaches have to be thoroughly investigated to shed new light on TGCT pathogenesis and treatment.
KEYWORDS:
Aurora B; GPR30; HMGA; PATZ1; testicular germ cells tumors
2.
Expert Rev Anticancer Ther. 2019 Oct;19(10):847-855. doi: 10.1080/14737140.2019.1674141. Epub 2019 Oct 11.
Cabozantinib for the treatment of hepatocellular carcinoma.
Abstract
Introduction: The randomized, placebo-controlled, phase III CELESTIAL trial demonstrated statistically and clinically significant improvement in overall survival with cabozantinib in patients with advanced hepatocellular carcinoma (HCC) previously treated with sorafenib. Most frequently reported adverse events included palmar-plantar erythrodysesthesia, hypertension, increased aspartate aminotransferase, fatigue, and diarrhea. Areas covered: In this review we analyze and discuss preclinical and clinical data of cabozantinib. We summarize efficacy and safety results of phase II and III trials of cabozantinib in the treatment of patients with advanced HCC and we present ongoing trials of cabozantinib in combination with checkpoint inhibitors. Expert opinion: Cabozantinib is a new second-line and the only third-line treatment for patients with advanced HCC, nevertheless some data are still missing to better inform clinical decisions on how to treat specific patient populations. Next trials designs will have to incorporate heavy efforts in terms of translational research to maximize the benefits of such treatments.
KEYWORDS:
AXL; Hepatocellular carcinoma; MET; angiogenesis; cabozantinib
3.
Expert Rev Anticancer Ther. 2019 Oct;19(10):889-898. doi: 10.1080/14737140.2019.1674142. Epub 2019 Oct 9.
The evolving role of maintenance therapy following autologous stem cell transplantation in multiple myeloma.
Abstract
Introduction: Maintenance therapy after autologous transplantation is a standard of care in newly diagnosed myeloma. However, there is no universal answer to the question of which maintenance strategy should be pursued after ASCT? Areas covered: We conducted a MEDLINE search using the medical subject headings 'multiple myeloma', 'autologous transplantation' and 'maintenance' to identify available data from clinical trials on the role of different maintenance strategies after autologous transplantation for the newly diagnosed disease. Expert opinion: A large meta-analysis demonstrated that lenalidomide prolongs progression-free and overall survival after autologous transplantation compared to observation/placebo. Further trials confirmed that lenalidomide maintenance increases rates of high-quality responses and one study demonstrated that lenalidomide maintenance improves outcomes regardless of cytogenetic risk. Although lenalidomide can cause side effects and is associated with an increased risk of second primary malignancies, its benefits outweigh the mentioned risks. The proteasome inhibitors ixazomib and bortezomib may partially overcome the negative effects of high-risk cytogenetics. Future trials will combine different agents and monoclonal antibodies during maintenance and will investigate whether minimal residual disease status can guide maintenance duration.
KEYWORDS:
Autologous transplantation; lenalidomide; maintenance; multiple myeloma
4.
Expert Rev Anticancer Ther. 2019 Oct;19(10):909-915. doi: 10.1080/14737140.2019.1677157. Epub 2019 Oct 14.
Have treatment protocols for primary CNS lymphoma advanced in the past 10 years.
Abstract
Introduction: Primary CNS lymphomas (PCNSL) are highly aggressive tumors and optimal treatment is not yet defined. For the last two decades, clinical trials have focused on developing efficient chemotherapy protocols with or without dose-reduced radiation to avoid late cognitive decline after whole brain radiotherapy (WBRT). Areas covered: This review addresses the question if these substantial developments have led to clinically relevant therapeutic improvement for PCNSL within the last decade. Expert opinion: The high risk of neurotoxic side effects of WBRT was further substantiated, and in most centers WBRT is omitted from first-line treatment in patients eligible for high-dose systemic methotrexate (HDMTX)-based chemotherapy. Intensified polychemotherapy regimens, particularly high-dose chemotherapy regimens with autologous stem cell transplantation (HD-ASCT), were investigated within prospective multicenter randomized trials and have achieved long-term disease control in a fraction of patients, but no significant progress was made for elderly patients, who are not able to tolerate intensified chemotherapy. Results on the efficacy of rituximab in PCNSL are conflicting; it did not show clinical benefit in a recent large prospective multicenter randomized trial. New substances such as immune-checkpoint inhibitors and targeted molecules are subject to investigation, but have not yet been implemented in clinical routine.
KEYWORDS:
HD-ASCT; PCNSL; consolidation therapy; methotrexate; rituximab
5.
Expert Rev Anticancer Ther. 2019 Oct;19(10):831-834. doi: 10.1080/14737140.2019.1677158. Epub 2019 Oct 12.
Death and the Miser: microbiota regulate the outcome of checkpoint inhibition immunotherapy.
KEYWORDS:
Checkpoint inhibition therapy; fecal transplant; microbiota; tumor immunology
6.
Expert Rev Anticancer Ther. 2019 Oct;19(10):899-908. doi: 10.1080/14737140.2019.1674143. Epub 2019 Oct 8.
An evidence-based analysis of the management of N0 neck in patients with cancer of the parotid gland.
Vartanian JG1, Gonçalves Filho J1, Kowalski LP1, Shah JP2, Suárez C3,4, Rinaldo A5, De Bree R6, Rodrigo JP7, Hamoir M8, Takes RP9, Mäkitie AA10,11,12, Zbären P13, Andreasen S14,15, Poorten VV16,17, Sanabria A18, Hellquist H19, Robbins KT20, Bödeker CC21, Silver C22, Ferlito A23.
Abstract
Introduction: Management of clinically negative neck (cN0) in patients with parotid gland cancer is controversial. Treatment options can include observation, elective neck dissection or elective radiotherapy. Areas covered: We addressed the treatment options for cN0 patients with parotid gland cancer. A literature review was undertaken to determine the optimal management of this group of patients. Expert opinion: Patients with parotid carcinoma and clinically negative neck have various options for their management. The analysis of tumor stage, histology and grade is essential to better define patients at risk for occult lymph node metastasis. These patients can be managed by surgery, radiotherapy or their combination, depending on the presence of risk factors, the moment at which such risk factors are detected, patient-related clinical conditions, medical provider expertise and institutional facilities.
KEYWORDS:
Salivary gland; elective neck treatment; neck dissection; parotid gland; radiotherapy
7.
Expert Rev Anticancer Ther. 2019 Oct;19(10):879-888. doi: 10.1080/14737140.2019.1671189. Epub 2019 Sep 27.
The use of intraperitoneal chemotherapy for gastric malignancies.
Abstract
Introduction: Gastric cancer is the fourth/fifth most common malignancy worldwide, with only a quarter of patients achieving a 5-year survival rate. It has been estimated that 15-50% or more of patients have peritoneal disease upon surgical exploration. Until the early 1990s, peritoneal metastasis was considered as terminal stage of the disease; in the late 1990s, selected patients with peritoneal metastasis were recategorized as local disease. Over the past two decades, the treatment of peritoneal involvement has transformed, and cytoreductive surgery plus intraperitoneal therapy have drastically altered the natural course of several malignancies. Areas covered: We performed a review of studies available on PubMed from 1 January 2014 to 31 July 2019 and the analysis of their reference citations. We describe the most current intraperitoneal chemotherapy opportunities in the treatment of gastric cancer: hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC), laparoscopic hyperthermic intraperitoneal chemotherapy (LHIPEC), neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), LHIPEC + NIPS, extensive intraoperative peritoneal lavage (EIPL), early postoperative intraperitoneal chemotherapy (EPIC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC). Expert opinion: Comprehensive treatment consisting of CRS combined with perioperative intraperitoneal/systemic chemotherapy can, today, be considered an effective strategy to improve the long-term survival of gastric cancer patients with peritoneal metastasis.
KEYWORDS:
EPIC; EPIL; HIPEC; NIPS; gastric cancer
8.
Expert Rev Anticancer Ther. 2019 Oct;19(10):835-846. doi: 10.1080/14737140.2019.1671190. Epub 2019 Oct 4.
Erdafitinib for the treatment of urothelial cancer.
Abstract
Introduction: Fibroblast growth-factor receptor (FGFR) inhibition is a promising strategy of treatment in urothelial cancer (UC). FGFR3 mutations or fusions (mut/fus) are common in luminal-1 UC subtype, which exhibits poor responses to immunotherapy. Erdafitinib is a potent and selective pan-FGFR tyrosine kinase inhibitor. Based on the results of the phase 2 BLC2001 trial (NCT02365597), in which erdafitinib showed an overall response rate of 40% in metastatic UC with FGFR3 mut/fus, it is the first approved targeted therapy in metastatic UC. Areas covered: This review covers the preclinical and clinical evidence for erdafitinib, summarizes the results of other FGFR inhibitors tested in UC and explores future perspectives of FGFR inhibition in UC. Expert opinion: In the era of precision medicine, erdafitinib approval marks a step forward in UC. Erdafitinib qualifies as a compelling comparator in the salvage therapy setting. Special attention must be paid to typical adverse class-effects of FGFR inhibitors. In the near future, in order to achieve an optimal selection of molecularly-altered tumors, it will be important to assess the performance of different diagnostic tools and to investigate the role of liquid biopsy. Combinations with immunotherapy represent a novel therapeutic opportunity being tested in ongoing trials.
KEYWORDS:
alterations; Erdafitinib; systemic therapy; targeted therapy; urothelial carcinoma
9.
Expert Rev Anticancer Ther. 2019 Oct;19(10):869-878. doi: 10.1080/14737140.2019.1670063. Epub 2019 Sep 26.
Liquid biopsies in pancreatic cancer.
Abstract
Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a disease of high lethality. Invasive tissue biopsies of primary or metastatic lesions remain the gold standard for diagnosis, but repeated sampling is infeasible. Noninvasive liquid biopsies offer new opportunities for early diagnosis for high-risk cohorts, and for the longitudinal analysis of tumor evolution and progression in patients on therapy. Liquid biopsies can capture tumor-associated components, such as circulating tumor DNA (ctDNA), extracellular vesicles (EVs), and circulating tumor cells (CTCs), each of which provides genomic and molecular information about the underlying PDAC that can potentially inform clinical decisions. Areas covered: Here, we reviewed current knowledge and recent technological advances regarding liquid biopsy in PDAC and mention the pitfalls and benefits in each methodology. We also discuss clinical correlative studies for diagnosis and prognosis in PDAC. Expert opinion:In pancreatic cancer where tissue samples are limited and repeated tissue biopsies are mostly invasive and infeasible, liquid biopsies opened a new window for tumor diagnosis, molecular stratification, and treatment monitoring. While none of the isolation and analysis methods have gained widespread clinical acceptance, it is imperative that the advantages and limitations of each platform for isolation and analysis of tumor associated components are taken into consideration.
KEYWORDS:
Cell-free DNA; circulating tumor cells; extracellular vesicles; liquid biopsies; pancreatic cancer
- PMID:
- 31533487
- PMCID:
- PMC6824837
- [Available on 2020-10-01]
- DOI:
- 10.1080/14737140.2019.1670063
- [Indexed for MEDLINE]
10.
Expert Rev Anticancer Ther. 2019 Oct;19(10):857-867. doi: 10.1080/14737140.2019.1667236. Epub 2019 Sep 24.
Tumor heterogeneity: does it matter?
Abstract
Introduction: It has long been recognized that tumors are composed of a mosaic of cells and numerous methods have been developed to detect tumor heterogeneity, including in situ hybridization, multi-regional sampling, cytological assays, and whole genome and single cell sequencing. Using these methods, heterogeneity has been observed at the genetic, epigenetic, and phenotypic level in numerous cancers. With the advent of deep sequencing technology, we now appreciate a greater complexity of distinct genotypes and phenotypes that drive the biological behavior of cancer. Despite decades of progress in detecting tumor heterogeneity, the question remains: to what extent does it matter? Areas covered: This review explores the evidence for and against the importance of tumor heterogeneity in three main areas: prognostication, development of targeted therapeutics and tumor resistance; summarizing current understanding before evaluating ongoing experimental and clinical developments. Expert opinion: Theoretical understanding and in vitro detection of intratumour heterogeneity promises much but is yet to translate into meaningful clinical benefit. However, the recent emergence of a host of technological innovations and upcoming clinical trials may soon change the landscape of this field.
KEYWORDS:
Cancer stem cell; drug resistance; liquid biopsy; tumor evolution; tumor heterogeneity
11.
Expert Rev Anticancer Ther. 2019 Feb;19(2):151-167. doi: 10.1080/14737140.2019.1559057. Epub 2018 Dec 28.
Prospects of targeted and immune therapies in SCLC.
Abstract
Introduction: Small cell lung cancer (SCLC) is a tumor with a poor prognosis, often diagnosed in an advanced stage. Despite aggressive treatment of early and locally advanced disease, SCLC often relapses. First line chemotherapy provides good response rates in advanced disease, but progression free and overall survival are limited. New drugs such as some targeted therapies and immune therapies are promising in SCLC. Areas covered: In this review, we discuss the preclinical rationale and trial data for targeted therapies and immune therapies in SCLC, with a specific focus on clinical trials. Expert commentary: Lack of identification of clear prognostic and predictive biomarkers has limited the advances in treatment efficacy. This has most likely been the main cause of failure for compounds tested so far. Due to the highly mutational profile and the rapid growth pattern of SCLC, immunotherapy combined with chemotherapy seems the most promising treatment option. Concerning targeted agents, achievements made so far are small, but DLL3-antibodies or combinations of PARPi and immunotherapy could be very promising. These promising strategies also need testing in limited disease.
KEYWORDS:
Checkpoint inhibitors; immune therapy; small cell lung cancer; targeted therapy; vaccination therapy
12.
Expert Rev Anticancer Ther. 2019 Feb;19(2):105-119. doi: 10.1080/14737140.2019.1561288. Epub 2019 Jan 15.
Oral and Oropharyngeal squamous cell carcinoma: prognostic and predictive parameters in the etiopathogenetic route.
Panarese I1, Aquino G2, Ronchi A1, Longo F3, Montella M1, Cozzolino I1, Roccuzzo G1, Colella G4, Caraglia M5, Franco R1.
Abstract
Oral and oropharyngeal squamous cell carcinoma (OSCC and OPSCC) represents an increasing problem in the global public health. Indeed, squamous cell carcinoma is the most frequent malignancy in oral cavity and 1 of the 10 most common cancers worldwide. According to the most recent GLOBOCAN estimate in Europe between 2012 and 2015, there was an overall increasing incidence and mortality for oral cancer, mostly HPV-related in the oropharyngeal region with evidence of significant differences from the prognostic and therapeutic point of view. Areas covered: Until now, the management of the patients is based on classical histologic parameters such as TNM and tumor grading, but new molecular and cell markers have been investigated to improve patients' treatment and survival. Therefore, there is a need for new biomarkers characterizing the cancer diversity, with the consequent possibility of patient stratification for specific treatment. Expert commentary: This review aims to discuss some of the most relevant and novel genetic, epigenetic, and histological prognostic biomarkers in oral cancer, highlighting the main differences between HPV-unrelated oral squamous cell carcinoma (OSCC) and HPV-related oropharyngeal squamous cell carcinoma (OPSCC) that may aid in stratifying prognostic subgroups and rationalizing treatment decisions.
KEYWORDS:
EGFR; PDL1; human papilloma virus; oral squamous cell carcinoma; orapharyngeal squamous cell carcinoma
13.
Expert Rev Anticancer Ther. 2019 Feb;19(2):191-203. doi: 10.1080/14737140.2019.1559059. Epub 2018 Dec 24.
Major vessel invasion by thyroid cancer: a comprehensive review.
Abstract
Introduction: Gross extrathyroidal extension of thyroid cancer is an indicator of a worse cancer prognosis and may lead to major vessel invasion (MVI) that represents an uncommon and highly morbid manifestation of disease progression. Areas covered: This review aims to evaluate the current literature reporting on thyroid cancer that exhibits MVI, with a focus on relevant patient and pathological characteristics, diagnostic evaluation, and management, of this uncommon but challenging thyroid cancer presentation. Expert commentary: Vascular invasion by thyroid cancer is uncommon and has a poor prognosis with high associated perioperative morbidity and mortality. When possible, surgery represents the best management strategy for thyroid cancer exhibiting MVI. In these cases, careful preoperative workup and surgical planning are required in order to balance the goals of maximizing cancer resection while minimizing perioperative mortality and morbidity. Future research should evaluate long-term outcomes following definitive treatment of locally advanced thyroid cancer exhibiting MVI.
KEYWORDS:
Major vessel invasion; extrathyroidal extension; superior vena cava syndrome; thyroid cancer
14.
Expert Rev Anticancer Ther. 2019 Feb;19(2):177-189. doi: 10.1080/14737140.2019.1559058. Epub 2018 Dec 21.
Sorafenib: key lessons from over 10 years of experience.
Abstract
Introduction: In 2005, sorafenib was the first targeted therapy approved for advanced renal cell carcinoma (RCC), transforming treatment. In hepatocellular carcinoma (HCC), for more than a decade, sorafenib remained the only approved systemic therapy to have demonstrated a survival benefit in first-line unresectable HCC. In 2013, sorafenib was the first targeted agent approved for patients with differentiated thyroid cancer (DTC) refractory to radioactive iodine treatment. Areas covered: This review discusses the development, advances, and challenges associated with sorafenib use in RCC, HCC, and DTC over the past decade. A search was performed on PubMed and key congresses as required, with no time limits. Expert commentary: Sorafenib has had a lasting impact on the therapeutic landscape of RCC, HCC, and DTC, and remains an important treatment option despite a rapidly evolving treatment landscape. Extensive clinical and real-world experience has been invaluable in improving patient management and maximizing benefit from treatment. Ongoing clinical trials continue to evaluate sorafenib in different settings, and in combination with other therapies in HCC and DTC. We have no doubt that sorafenib will continue to be an important treatment option in the coming years.
KEYWORDS:
Differentiated thyroid cancer; anti-angiogenic; hepatocellular carcinoma; renal cell carcinoma; sorafenib
15.
Expert Rev Anticancer Ther. 2019 Feb;19(2):121-138. doi: 10.1080/14737140.2019.1552138. Epub 2018 Dec 3.
The evolving role of receptors as predictive biomarkers for metastatic breast cancer.
Abstract
In breast cancer, estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) are essential biomarkers to predict response to endocrine and anti-HER2 therapies, respectively. In metastatic breast cancer, the use of these receptors and targeted therapies present additional challenges: temporal heterogeneity, together with limited sampling methodologies, hinders receptor status assessment, and the constant evolution of the disease invariably leads to resistance to treatment. Areas covered: This review summarizes the genomic abnormalities in ER and HER2, such as mutations, amplifications, translocations, and alternative splicing, emerging as novel biomarkers that provide an insight into underlying mechanisms of resistance and hold potential predictive value to inform treatment selection. We also describe how liquid biopsies for sampling of circulating markers and ultrasensitive detection technologies have emerged which complement ongoing efforts for biomarker discovery and analysis. Expert commentary: While evidence suggests that genomic aberrations in ER and HER2 could contribute to meeting the pressing need for better predictive biomarkers, efforts need to be made to standardize assessment methods and better understand the resistance mechanisms these markers denote. Taking advantage of emerging technologies, research in upcoming years should include prospective trials incorporating these predictors into the study design to validate their potential clinical value.
KEYWORDS:
ER; HER2; biomarkers; hormone receptors; metastatic breast cancer
16.
Expert Rev Anticancer Ther. 2019 Feb;19(2):169-175. doi: 10.1080/14737140.2019.1548939. Epub 2018 Nov 29.
The molecular characterization and therapeutic strategies of papillary renal cell carcinoma.
Abstract
Introduction: Papillary renal cell carcinoma (pRCC) is an important subtype of kidney cancer with a problematic pathological classification and highly variable clinical behavior. In this review, we summarize the current progression on pRCC in molecular level. Our findings highlight the need for molecular markers to accurately subtype pRCC and may lead to the development of more targeted agents and better patient stratification in clinical trials for pRCC. Areas covered: This review highlights the need for molecular markers to accurately subtype PRCC and may lead to the development of more targeted agents and better patient stratification in clinical trials for pRCC. Expert commentary: There are mainly two subtypes of pRCC based on histology. However, little is known about the genetic characterization of the sporadic forms of pRCC and there are currently no standard forms of therapy for patients with advanced disease. Both MET inhibitors and immunotherapy may be effective in advanced pRCC treatment. Therefore, understanding the molecular basis of pRCC and identifying the main goal of treatment is crucial for the selection of the best strategy.
KEYWORDS:
Papillary renal cell carcinoma; genetic; mutation; survival prognosis; the cancer genome atlas
17.
Expert Rev Anticancer Ther. 2019 Feb;19(2):139-149. doi: 10.1080/14737140.2019.1552139. Epub 2018 Dec 4.
Cancer epigenetics and the potential of epigenetic drugs for treating solid tumors.
Abstract
Introduction: Epigenetic modification without DNA sequence mutation plays an important role in cancer development. Some small molecular inhibitors targeting key epigenetic molecules have been approved by the Food and Drug Administration to treat hematological malignancies. However, the anticancer effects of these drugs on solid tumors are not satisfactory, and the mechanisms of action remain largely unknown. Areas covered: The review summarizes the latest research on cancer epigenetics and discusses the potentials and limitations of using epigenetic drugs to treat solid tumors. An analysis of possible reasons for epigenetic drug treatment failure in solid tumors in some clinical trials is discussed along with prospects for future development. Expert commentary: Next-generation small molecule inhibitors will target novel epigenetic regulators with high cancer specificity. Combined modalities exploiting epigenetic drugs with chemo-/radiotherapy, molecular-targeting drugs, and immunotherapy will be able to effectively treat solid tumors in the near future.
KEYWORDS:
Epigenetics; combination therapy; epigenetic drugs; hematologic malignancies; solid tumors
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