Androgen Receptor Variants Mediate DNA Repair after Prostate Cancer Irradiation
In prostate cancer, androgen deprivation therapy (ADT) enhances the cytotoxic effects of radiotherapy. This effect is associated with weakening of the DNA damage response (DDR) normally supported by the androgen receptor. As a significant number of patients will fail combined ADT and radiotherapy, we hypothesized that DDR may be driven by androgen receptor splice variants (ARV) induced by ADT. Investigating this hypothesis, we found that ARVs increase the clonogenic survival of prostate cancer cells after irradiation in an ADT-independent manner. Notably, prostate cancer cell irradiation triggers binding of ARV to the cata...
Source: Cancer Research - September 14, 2017 Category: Cancer & Oncology Authors: Yi Yin, Rui Li, Kangling Xu, Sentai Ding, Jeffrey Li, GuemHee Baek, Susmita G. Ramanand, Sam Ding, Zhao Liu, Yunpeng Gao, Mohammed S. Kanchwala, Xiangyi Li, Ryan Hutchinson, Xihui Liu, Solomon L. Woldu, Chao Xing, Neil B. Desai, Felix Y. Feng, Sandeep Bur Tags: Priority Report Source Type: research
Methods of Academic Course Planning for Cancer Biology PhD Students to Enhance Knowledge of Clinical Oncology
In this study, electronic surveys were sent to faculty and students at PhD training programs, assessing their institution's methods of clinical oncology education and their perspective on optimal approaches to clinical oncology education. Only 40.0% of students reported any clinical oncology component to their institution's training, and only 26.5% had a clinician on their graduate advisory committee. Forty-three percent of students believed that they had a good understanding for translating basic science research into clinical practice, and 77.2% of all participants believed dual degree MD/PhD students were superior to Ph...
Source: Cancer Research - September 14, 2017 Category: Cancer & Oncology Authors: Malcolm D. Mattes, Elizabeth Swart, Steven M. Markwell, Sijin Wen, Linda C. Vona-Davis Tags: Perspective Source Type: research
Highlights from Recent Cancer Literature
(Source: Cancer Research)
Source: Cancer Research - September 14, 2017 Category: Cancer & Oncology Tags: Breaking Advances Source Type: research
Correction: Connective Tissue Growth Factor Activates Pluripotency Genes and Mesenchymal-Epithelial Transition in Head and Neck Cancer Cells
(Source: Cancer Research)
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Tags: Corrections Source Type: research
Correction: Chromosome Instability Modulated by BMI1-AURKA Signaling Drives Progression in Head and Neck Cancer
(Source: Cancer Research)
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Tags: Corrections Source Type: research
Correction: Germline BAP1 Mutational Landscape of Asbestos-Exposed Malignant Mesothelioma Patients with Family History of Cancer
(Source: Cancer Research)
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Tags: Corrections Source Type: research
Water Concentration Analysis of the Surgical Margin—Response
(Source: Cancer Research)
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Authors: Gerwin J. Puppels Tags: Letters to the Editor Source Type: research
Water Concentration Analysis of the Surgical Margin—Letter
(Source: Cancer Research)
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Authors: C. Murali Krishna, Aditi Sahu Tags: Letters to the Editor Source Type: research
Multinuclear NMR and MRI Reveal an Early Metabolic Response to mTOR Inhibition in Sarcoma
In this study, we took a multimodality approach to evaluate the phenotypic effects and metabolic changes that occur with inhibition of the PI3K/mTOR pathway. Its central role in regulating glycolysis in human sarcomas was evaluated by short- and long-term rapamycin treatment in sarcoma cell lines. We observed an overall decrease in lactate production in vitro, followed by cell growth inhibition. In vivo, we observed a similar quantitative reduction in lactate production as monitored by hyperpolarized MRI, also followed by tumor size changes. This noninvasive imaging method could distinguish reduced cell proliferation from ...
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Authors: Valentina Di Gialleonardo, Hannah N. Aldeborgh, Vesselin Miloushev, Kelly M. Folkers, Kristin Granlund, William D. Tap, Jason S. Lewis, Wolfgang A. Weber, Kayvan R. Keshari Tags: Tumor and Stem Cell Biology Source Type: research
Disrupting Androgen Receptor Signaling Induces Snail-Mediated Epithelial-Mesenchymal Plasticity in Prostate Cancer
Epithelial-to-mesenchymal plasticity (EMP) has been linked to metastasis, stemness, and drug resistance. In prostate cancer, EMP has been associated with both suppression and activation of the androgen receptor (AR) signaling. Here we investigated the effect of the potent AR antagonist enzalutamide on EMP in multiple preclinical models of prostate cancer and patient tissues. Enzalutamide treatment significantly enhanced the expression of EMP drivers (ZEB1, ZEB2, Snail, Twist, and FOXC2) and mesenchymal markers (N-cadherin, fibronectin, and vimentin) in prostate cancer cells, enhanced prostate cancer cell migration, and ind...
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Authors: Lu Miao, Lin Yang, Rui Li, Daniel N. Rodrigues, Mateus Crespo, Jer-Tsong Hsieh, Wayne D. Tilley, Johann de Bono, Luke A. Selth, Ganesh V. Raj Tags: Tumor and Stem Cell Biology Source Type: research
The p53/p21 Complex Regulates Cancer Cell Invasion and Apoptosis by Targeting Bcl-2 Family Proteins
The tumor suppressor p53 binds prosurvival Bcl-2 family proteins such as Bcl-w and Bcl-XL to liberate Bax, which in turn exerts proapoptotic or anti-invasive functions depending on stress context. On the basis of our previous finding that p53 interacts with p21, we investigated the possible involvement of p21 in these functions. Here, we report that although p53 can bind Bcl-w alone, it requires p21 to liberate Bax to suppress cell invasion and promote cell death. p21 bound Bcl-w, forming a p53/p21/Bcl-w complex in a manner that maintained all pairwise p53/p21, p21/Bcl-w, and p53/Bcl-w interactions. This allowed Bax libera...
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Authors: Eun Mi Kim, Chan-Hun Jung, Jongdoo Kim, Sang-Gu Hwang, Jong Kuk Park, Hong-Duck Um Tags: Tumor and Stem Cell Biology Source Type: research
NOTCH1 Signaling Regulates Self-Renewal and Platinum Chemoresistance of Cancer Stem-like Cells in Human Non-Small Cell Lung Cancer
Cancer stem–like cells (CSC) are thought to drive tumor initiation, metastasis, relapse, and therapeutic resistance, but their specific pathogenic characters in many cancers, including non–small cell lung cancer (NSCLC), have yet to be well defined. Here, we develop findings that the growth factor HGF promotes CSC sphere formation in NSCLC cell populations. In patient-derived sphere-forming assays (PD-SFA) with HGF, CD49f and CD104 were defined as novel markers of lung CSC (LCSC). In particular, we isolated a subpopulation of CD166+CD49fhiCD104−Lin− LCSC present in all human specimens of NSCLC examined, regardless ...
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Authors: Yun Zhang, Wei Xu, Huiqin Guo, Yanmei Zhang, Yuexi He, Sau Har Lee, Xin Song, Xiaoyan Li, Yongqing Guo, Yunlong Zhao, Cheng Ding, Fei Ning, Yuanyuan Ma, Qun-Ying Lei, Xiaoyu Hu, Shengnan Li, Wei Guo Tags: Tumor and Stem Cell Biology Source Type: research
Combination Therapy Targeting BCL6 and Phospho-STAT3 Defeats Intratumor Heterogeneity in a Subset of Non-Small Cell Lung Cancers
Oncogene-specific changes in cellular signaling have been widely observed in lung cancer. Here, we investigated how these alterations could affect signaling heterogeneity and suggest novel therapeutic strategies. We compared signaling changes across six human bronchial epithelial cell (HBEC) strains that were systematically transformed with various combinations of TP53, KRAS, and MYC—oncogenic alterations commonly found in non–small cell lung cancer (NSCLC). We interrogated at single-cell resolution how these alterations could affect classic readouts (β-CATENIN, SMAD2/3, phospho-STAT3, P65, FOXO1, and phospho-ERK1/2) ...
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Authors: Dhruba Deb, Satwik Rajaram, Jill E. Larsen, Patrick D. Dospoy, Rossella Marullo, Long Shan Li, Kimberley Avila, Fengtian Xue, Leandro Cerchietti, John D. Minna, Steven J. Altschuler, Lani F. Wu Tags: Tumor and Stem Cell Biology Source Type: research
Integrative Cancer Pharmacogenomics to Infer Large-Scale Drug Taxonomy
Identification of drug targets and mechanism of action (MoA) for new and uncharacterized anticancer drugs is important for optimization of treatment efficacy. Current MoA prediction largely relies on prior information including side effects, therapeutic indication, and chemoinformatics. Such information is not transferable or applicable for newly identified, previously uncharacterized small molecules. Therefore, a shift in the paradigm of MoA predictions is necessary toward development of unbiased approaches that can elucidate drug relationships and efficiently classify new compounds with basic input data. We propose here ...
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Authors: Nehme El-Hachem, Deena M.A. Gendoo, Laleh Soltan Ghoraie, Zhaleh Safikhani, Petr Smirnov, Christina Chung, Kenan Deng, Ailsa Fang, Erin Birkwood, Chantal Ho, Ruth Isserlin, Gary D. Bader, Anna Goldenberg, Benjamin Haibe-Kains Tags: Therapeutics, Targets, and Chemical Biology Source Type: research
ATM Deficiency Is Associated with Sensitivity to PARP1- and ATR Inhibitors in Lung Adenocarcinoma
Defects in maintaining genome integrity are a hallmark of cancer. The DNA damage response kinase ATM is frequently mutated in human cancer, but the significance of these events to chemotherapeutic efficacy has not been examined deeply in whole organism models. Here we demonstrate that bi-allelic Atm deletion in mouse models of Kras-mutant lung adenocarcinoma does not affect cisplatin responses. In marked contrast, Atm-deficient tumors displayed an enhanced response to the topoisomerase-II poison etoposide. Moreover, Atm-deficient cells and tumors were sensitive to the PARP inhibitor olaparib. This actionable molecular addi...
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Authors: Anna Schmitt, Gero Knittel, Daniela Welcker, Tsun–Po Yang, Julie George, Michael Nowak, Uschi Leeser, Reinhard Buttner, Sven Perner, Martin Peifer, Hans Christian Reinhardt Tags: Therapeutics, Targets, and Chemical Biology Source Type: research
