Background The role of socioeconomic factors as determinants of oncology consultations for advanced cancers in public payer health care systems is unknown. This study examined the association between material deprivation and receipt of cancer care among patients with advanced gastrointestinal (GI) cancer. Methods This was a population‐based, retrospective cohort study of noncuratively treated patients with GI cancer diagnosed from 2007 to 2017. Material deprivation, representing income, quality...
Mon Aug 03, 2020 21:59
British Journal of Cancer, Published online: 05 August 2020; doi:10.1038/s41416-020-1017-1Development of an artificial antibody specific for HLA/peptide complex derived from cancer stem-like cell/cancer-initiating cell antigen DNAJB8
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Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
Wed Jul 29, 2020 10:00
Abstract Background This systematic review and meta-analysis aimed to evaluate the association between pretreatment body mass index (BMI) and clinical outcomes in cancer patients treated with immune checkpoint inhibitors (ICIs). Methods Systematical searches of PubMed, Embase, and the Cochrane Library databases were carried out. Studies reporting on...
Tue Aug 04, 2020 03:00
Growing data indicate an association between periodontal disease and the development of cancer. However, the evidence for colorectal cancer has been inconsistent and longitudinal study examining its precursor lesions is lacking. We prospectively collected information on periodontal disease and number of tooth loss in the Nurses' Health Study (1992–2002) and the Health Professionals Follow-up Study (1992–2010). Polyp diagnosis was acquired via self-reported questionnaires and confirmed through review...
Tue Aug 04, 2020 10:05
Ductal carcinoma in situ (DCIS), which accounts for one out of every five new breast cancer diagnoses, will progress to potentially lethal invasive ductal carcinoma (IDC) in about 50% of cases. Vitamin D compounds have been shown to inhibit progression to IDC in the MCF10DCIS model. This inhibition appears to involve a reduction in the cancer stem cell–like population in MCF10DCIS tumors. To identify genes that are involved in the vitamin D effects, a global transcriptomic analysis was undertaken...
Tue Aug 04, 2020 10:05
Global interest in genetic testing for cancer susceptibility genes (CSG) has surged with falling costs, increasing awareness, and celebrity endorsement. Current access to genetic testing is based on clinical criteria/risk model assessment which uses family history as a surrogate. However, this approach is fraught with inequality, massive underutilization, and misses 50% CSG carriers. This reflects huge missed opportunities for precision prevention. Early CSG identification enables uptake of risk-reducing...
Tue Aug 04, 2020 10:05
The human gut microbiome intimately complements the human genome and gut microbial factors directly influence health and disease. Here we outline how the gut microbiota uniquely contributes to cancer etiology by processing products of human drug and endobiotic metabolism. We formally propose that the reactions performed by the gut microbiota should be classified as "Phase IV xenobiotic and endobiotic metabolism." Finally, we discuss new data on the control of cancer by the inhibition of gut microbial...
Tue Aug 04, 2020 10:05
Head and neck squamous cell carcinoma (HNSCC) was the 7th most common malignancy worldwide in 2018 and despite therapeutic advances, the overall survival rate for oral squamous cell carcinoma (OSCC; ~50%) has remained unchanged for decades. The most common types are OSCC and oropharyngeal squamous cell carcinoma (OPSCC, survival rate ~85%). Tobacco smoking is a major risk factor of HNSCC. In the developed world, the incidence of OSCC is declining as a result of tobacco cessation programs. However,...
Tue Aug 04, 2020 10:05
Identifying persons at high risk for gastric cancer is needed for targeted interventions for prevention and control in low-incidence regions. Combining ethnic/cultural factors with conventional gastric cancer risk factors may enhance identification of high-risk persons. Data from a prior case–control study (40 gastric cancer cases and 100 controls) were used. A "conventional model" using risk factors included in the Harvard Cancer Risk Index's gastric cancer module was compared with a "parsimonious...
Tue Aug 04, 2020 10:05
Prostate cancer chemoprevention by sulforaphane, which is a metabolic by-product of glucoraphanin found in broccoli, in preclinical models is associated with induction of both apoptosis and autophagy. However, the molecular mechanism underlying sulforaphane-mediated autophagy, which is protective against apoptotic cell death by this phytochemical, is still poorly understood. This study demonstrates a role for lysosome-associated membrane protein 2 (LAMP2) in sulforaphane-mediated autophagy and apoptosis....
Tue Aug 04, 2020 10:05
Mounting evidence indicates a potential beneficial effect of vigorous-intensity physical activity on hepatocellular carcinoma (HCC). However, the association between moderate-intensity physical activity, such as brisk walking, and the risk of HCC remains largely unknown. Two prospective cohorts of 77,535 women from the Nurses' Health Study and 44,540 men from the Health Professionals Follow-up Study were included. Weekly time spent on physical activities were updated biennially. The Cox proportional...
Tue Aug 04, 2020 10:05
Abstract Androgen receptor (AR) signaling is considered to be crucial for the pathogenesis of hepatocellular carcinoma (HCC) with obvious sexual dimorphism. Pre‐mRNA processing factor 6 (PRPF6) was identified as a coactivator of AR. However, what is the molecular mechanism underlying the modulation function of PRPF6 on AR‐mediated transcriptional activity in HCC needs to be further clarified. In this study, we analyzed the data from TCGA to show that PRPF6 is highly expressed in HCC. The highly...
Mon Aug 03, 2020 22:32
Publication date: Available online 3 August 2020Source: European Journal of Surgical OncologyAuthor(s): B. Jeremiasse, C.H. van den Bosch, M.W.H.A. Wijnen, C.E.J. Terwisscha van Scheltinga, M.F. Fiocco, A.F.W. van der Steeg
Tue Aug 04, 2020 15:40
Future Oncology, Ahead of Print.
Tue Aug 04, 2020 11:46
Related Articles A meta-analysis and in silico analysis of polymorphic variants conferring breast cancer risk in the Indian subcontinent. Future Oncol. 2020 Aug 01;: Authors: Sengupta D, Banerjee S, Mukhopadhyay P, Guha U, Ganguly K, Bhattacharjee S, Sengupta M Abstract Background: Genetic association studies on breast cancer on the Indian subcontinent have yielded conflicting results, and the precise effect of these variants on breast cancer...
Tue Aug 04, 2020 15:10
Related Articles Cancer stem cell plasticity in glioblastoma multiforme: a perspective on future directions in oncolytic virotherapy. Future Oncol. 2020 Aug 02;: Authors: Kim DS Abstract The cancer stem cell (CSC) hypothesis suggests that a rare population of stem-like cells underpin tumorigenesis. Oncolytic viruses (OVs) demonstrate novel mechanisms of targeting the elusive CSCs with greater selectivity - promising therapeutic potential against...
Tue Aug 04, 2020 15:10
Abstract Identification of ancestry‐specific pathogenic variants is imperative for diagnostic, treatment, management and prevention strategies, and to understand penetrance/modifiers on risk. Our study aimed to determine the clinical significance of a recurrent BRCA1 c.442‐22_442‐13del variant of unknown significance identified among 13 carriers from six Chinese families, all with a significant history of breast and/or ovarian cancer. We further aimed to establish whether this was due to a founder...
Mon Aug 03, 2020 19:10
ABSTRACT Disease recurrence in surgically treated lung adenocarcinoma (AC) remains high. New approaches for risk stratification beyond tumor stage are needed. Gene expression‐based AC subtypes like the TCGA terminal‐respiratory unit (TRU), proximal‐inflammatory (PI), and proximal‐proliferative (PP) subtypes, have been associated with prognosis, but show methodological limitations for robust clinical use. We aimed to derive a platform independent single sample predictor (SSP) for molecular subtype...
Mon Aug 03, 2020 19:09
ABSTRACT Predicting oncologic outcome is challenging due to the diversity of cancer histologies and the complex network of underlying biological factors. In this study, we determine whether machine learning can extract meaningful associations between oncologic outcome and clinical trial, drug‐related biomarker, and molecular profile information. We analyzed therapeutic clinical trials corresponding to 1,102 oncologic outcomes from 104,758 cancer patients with advanced colorectal adenocarcinoma,...
Mon Aug 03, 2020 19:08
Journal of Adolescent and Young Adult Oncology, Ahead of Print.
Mon Aug 03, 2020 10:00
Journal of Adolescent and Young Adult Oncology, Ahead of Print.
Wed Jul 29, 2020 10:00
Abstract Cancer survivors are a growing population that may particularly benefit from nutrition and lifestyle interventions. Community-based programs teaching healthy cooking skills are increasingly popular and offer an opportunity to support survivors within communities. The objective of this study is to describe the curriculum and implementation of a cooking class program designed for cancer survivors, housed within an established community-based organization. First, we evaluated...
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Hepatocellular carcinoma (HCC) is one of the most prevalent common cancer worldwide with high mortality. Transforming growth factor-β (TGF-β) signaling pathway was reported dysregulated during liver cancer for...
Tue Aug 04, 2020 03:00
Abstract Extracellular vesicle (EV) has received increasing attention over the last decade. However, biomarkers and mechanisms underlying remain largely limited. Three microarray profiles, GSE78718 (K562 leukemia cell line), GSE45301 (U87-MG glioblastoma cell line), and GSE9589 (SW480 colon cancer cell line), were analyzed for the overlapped differentially expressed genes (DEGs). SurvExpress was used for the prognostic analysis of hub genes signature. Predicted transcription...
Tue Aug 04, 2020 03:00
Pilocytic astrocytomas as well as other pediatric low-grade gliomas (pLGG) exhibit genetic events leading to aberrant activation of the MAPK pathway. The most common alterations are KIAA1549:BRAF fusions and BRAFV600E and NF1 mutations. Novel drugs targeting the MAPK pathway (MAPKi) are prime candidates for the treatment of these single-pathway diseases. We aimed to develop an assay suitable for preclinical testing of MAPKi in pLGGs with the goal to identify novel MAPK pathway–suppressing synergistic...
Tue Aug 04, 2020 10:05
Cyclin-dependent kinases 4 and 6 (CDK4/6) have emerged as important therapeutic targets. Pharmacologic inhibitors of these kinases function to inhibit cell-cycle progression and exert other important effects on the tumor and host environment. Because of their impact on the cell cycle, CDK4/6 inhibitors (CDK4/6i) have been hypothesized to antagonize the antitumor effects of cytotoxic chemotherapy in tumors that are CDK4/6 dependent. However, there are multiple preclinical studies that illustrate potent...
Tue Aug 04, 2020 10:05
HER2-positive breast cancer is currently managed with chemotherapy in combination with specific anti-HER2 therapies, including trastuzumab. However, a high percentage of patients with HER2-positive tumors do not respond to trastuzumab (primary resistance) or either recur (acquired resistance), mostly due to molecular alterations in the tumor that are either unknown or undetermined in clinical practice. Those alterations may cause the tumor to be refractory to treatment with trastuzumab, promoting...
Tue Aug 04, 2020 10:05
The camptothecin derivatives topoisomerase I (TOP1) inhibitors, irinotecan and topotecan, are FDA approved for the treatment of colorectal, ovarian, lung and breast cancers. Because of the chemical instability of camptothecins, short plasma half-life, drug efflux by the multidrug-resistance ABC transporters, and the severe diarrhea produced by irinotecan, indenoisoquinoline TOP1 inhibitors (LMP400, LMP776, and LMP744), which overcome these limitations, have been developed and are in clinical development....
Tue Aug 04, 2020 10:05
Surgical resection is currently the only potentially curative option for patients with pancreatic cancer. However, the 5-year survival rate after resection is only 25%, due in part to high rates of R1 resections, in which cells are left behind at the surgical margin, resulting in disease recurrence. Fluorescence-guided surgery (FGS) has emerged as a method to reduce incomplete resections and improve intraoperative assessment of cancer. Mucin-16 (MUC16), a protein biomarker highly overexpressed in...
Tue Aug 04, 2020 10:05
Since the discovery of CHD1L in 2008, it has emerged as an oncogene implicated in the pathology and poor prognosis of a variety of cancers, including gastrointestinal cancers. However, a mechanistic understanding of CHD1L as a driver of colorectal cancer has been limited. Until now, there have been no reported inhibitors of CHD1L, also limiting its development as a molecular target. We sought to characterize the clinicopathologic link between CHD1L and colorectal cancer, determine the mechanism(s)...
Tue Aug 04, 2020 10:05
Frequent GNAQ and GNA11 mutations in uveal melanoma hyperactivate the MEK–ERK signaling pathway, leading to aberrant regulation of cyclin-dependent kinases (CDK) and cell-cycle progression. MEK inhibitors (MEKi) alone show poor efficacy in uveal melanoma, raising the question of whether downstream targets can be vertically inhibited to provide long-term benefit. CDK4/6 selective inhibitors are FDA-approved in patients with estrogen receptor (ER)–positive breast cancer in combination with ER antagonists/aromatase...
Tue Aug 04, 2020 10:05
The PI3K pathway is considered a master regulator for cancer due to its frequent activation, making it an attractive target for pharmacologic intervention. While substantial efforts have been made to develop drugs targeting PI3K signaling, few drugs have been able to achieve the inhibition necessary for effective tumor control at tolerated doses. HSP90 is a chaperone protein that is overexpressed and activated in many tumors and as a consequence, small-molecule ligands of HSP90 are preferentially...
Tue Aug 04, 2020 10:05
Although gemcitabine is the cornerstone of care for pancreatic ductal adenocarcinoma (PDA), patients lack durable responses and relapse is inevitable. While the underlying mechanisms leading to gemcitabine resistance are likely to be multifactorial, there is a strong association between activating gemcitabine metabolism pathways and clinical outcome. This study evaluated casein kinase 1 delta (CK1) as a potential therapeutic target for PDA and bladder cancer, in which CK1 is frequently overexpressed....
Tue Aug 04, 2020 10:05
Little is known about the role of epithelial membrane protein-2 (EMP2) in breast cancer development or progression. In this study, we tested the hypothesis that EMP2 may regulate the formation or self-renewal of breast cancer stem cells (BCSC) in the tumor microenvironment. In silico analysis of gene expression data demonstrated a correlation of EMP2 expression with known metastasis-related genes and markers of cancer stem cells (CSC) including aldehyde dehydrogenase (ALDH). In breast cancer cell...
Tue Aug 04, 2020 10:05
Focal adhesion kinase (FAK) promotes cancer cell growth and metastasis. We previously reported that FAK inhibition by the selective inhibitor VS-4718 exerted antileukemia activities in acute myeloid leukemia (AML). The mechanisms involved, and whether VS-4718 potentiates efficacy of other therapeutic agents, have not been investigated. Resistance to apoptosis inducted by the BCL-2 inhibitor ABT-199 (venetoclax) in AML is mediated by preexisting and ABT-199–induced overexpression of MCL-1 and BCL-XL....
Tue Aug 04, 2020 10:05
The next-generation antiandrogen drugs, XTANDI (enzalutamide), ZYTIGA (abiraterone acetate), ERLEADA (apalutamide) and NUBEQA (darolutamide) extend survival times and improve quality of life in patients with advanced prostate cancer. Despite these advances, resistance occurs frequently and there is currently no definitive cure for castration-resistant prostate cancer. Our previous studies identified that similar mechanisms of resistance to enzalutamide or abiraterone occur following treatment and...
Tue Aug 04, 2020 10:05
Multiple myeloma is a hematologic cancer that disrupts normal bone marrow function and has multiple lines of therapeutic options, but is incurable as patients ultimately relapse. We developed a novel antibody–drug conjugate (ADC) targeting CS-1, a protein that is highly expressed on multiple myeloma tumor cells. The anti–CS-1 mAb specifically bound to cells expressing CS-1 and, when conjugated to a cytotoxic pyrrolobenzodiazepine payload, reduced the viability of multiple myeloma cell lines in vitro....
Tue Aug 04, 2020 10:05
XPO1 inhibitors have shown promise in cancer treatment, but mechanisms of resistance to these drugs are not well understood. In this study, we established selective inhibitors of nuclear export (SINE)-resistant ovarian cancer cell lines from in vivo mouse tumors and determined the mechanisms of adaptive XPO1 inhibitor resistance using protein and genomic arrays. Pathway analyses revealed upregulation of the NRG1/ERBB3 pathway in SINE-resistant cells. Depletion of ERBB3 using siRNAs restored the antitumor...
Tue Aug 04, 2020 10:05
Glycosylation is a complex multienzyme-related process that is frequently deregulated in cancer. Aberrant glycosylation can lead to the generation of novel tumor surface–specific glycotopes that can be targeted by antibodies. Murine DS6 mAb (muDS6) was generated from serous ovary adenocarcinoma immunization. It recognizes CA6, a Mucin-1 (MUC1)-associated sialoglycotope that is highly detected in breast, ovarian, lung, and bladder carcinomas. SAR566658 antibody–drug conjugate (ADC) is a humanized...
Tue Aug 04, 2020 10:05
Metastasis development is the leading cause of cancer-related mortality in pancreatic ductal adenocarcinoma (PDAC) and yet, few preclinical systems to recapitulate its full spreading process are available. Thus, modeling of tumor progression to metastasis is urgently needed. In this work, we describe the generation of highly metastatic PDAC patient-derived xenograft (PDX) mouse models and subsequent single-cell RNA-sequencing (RNA-seq) of circulating tumor cells (CTC), isolated by human HLA sorting,...
Tue Aug 04, 2020 10:05
Despite significant progress in understanding the genetic landscape of T-cell acute lymphoblastic leukemia (T-ALL), the discovery of novel therapeutic targets has been difficult. Our results demonstrate that the levels of PIM1 protein kinase is elevated in early T-cell precursor ALL (ETP-ALL) but not in mature T-ALL primary samples. Small molecule PIM inhibitor (PIMi) treatment decreases leukemia burden in ETP-ALL. However, of animals carrying ETP-ALL with PIMi was not curative. To model other pathways...
Tue Aug 04, 2020 19:45
Abstract Withaferin A (WA) is a naturally occurring steroidal lactone with proven cancer chemopreventive activity in preclinical models of different cancers including prostate adenocarcinoma. Previously we compared the RNA‐seq data from control and WA‐treated 22Rv1 human prostate cancer cells to identify mechanistic targets of this phytochemical. The Gene Ontology pathway analysis of the RNA‐seq data revealed significant upregulation of genes associated with autophagy upon WA treatment in 22Rv1...
Mon Aug 03, 2020 11:45
Abstract Objective To determine the levels of fear of cancer in women who were referred for colposcopy and to determine validity and reliability of the Cancer Worry Scale (CWS) in gynaecology patients. Methods The study was conducted between March‐November 2017 with 200 women at the Gynaecologic Oncology Clinic at Akdeniz University Hospital in Turkey. Reliability analysis, confirmatory factor analyses, and multidimensional sum‐score estimation were used for psychometric analyses. One‐way...
Mon Aug 03, 2020 17:27
Abstract Objective To examine whether routine assessment of distress, recommended as part of comprehensive cancer care, is utilised equally with culturally and linguistically diverse (CALD) versus non‐CALD people living with cancer. Methods A medical records review of all patients attending cancer‐specific treatment units at a single tertiary hospital in Melbourne, Australia between 2015‐2018. Recording of administration of the Distress Thermometer and Problem Checklist (DT and PC) was...
Mon Aug 03, 2020 17:26
Abstract Objective To describe innovative models of psychosocial care delivery that align with published Standards of Psychosocial Care of Children with Cancer and their Families, in efforts to bridge the divide between research and practice. Methods The Mattie Miracle Cancer Foundation, in partnership with the American Psychosocial Oncology Society reviewed 22 letters of intent and 13 full grants and awarded small grants to researchers with high quality projects that aimed to implement...
Mon Aug 03, 2020 17:25
One-third of patients with pancreatic cancer has unresectable locally advanced disease at the time of diagnosis, and current treatment for these patients consists of a combination of chemotherapy and radiation therapy [1,2]. Historically, gemcitabine has been used as first-line chemotherapy after a pivotal multi-institutional trial showed both substantial clinical benefit and modestly improved survival with gemcitabine compared to 5-fluorouracil [3]. Recently, multiagent chemotherapy regimens have...
Tue Aug 04, 2020 03:00
The human PUF-family proteins, PUM1 and PUM2, post-transcriptionally regulate gene expression by binding to a PUM recognition element (PRE) in the 3’ UTR of target mRNAs. Hundreds of PUM1/2 targets have been identified from changes in steady state RNA levels; however, prior studies could not differentiate between the contributions of changes in transcription and RNA decay rates. We applied metabolic labeling to measure changes in RNA turnover in response to depletion of PUM1/2, showing that human...
Tue Aug 04, 2020 21:21
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