Read by QxMD icon Read

Oncogene addiction

Debolina Ganguly, Meiyun Fan, Chuan He Yang, Blazej Zbytek, David Finkelstein, Martine F Roussel, Lawrence M Pfeffer
Glioma-Initiating Cells (GICs) are thought to be responsible for tumor initiation, progression and recurrence in glioblastoma (GBM). In previous studies, we reported the constitutive phosphorylation of the STAT3 transcription factor in GICs derived from GBM patient-derived xenografts, and that STAT3 played a critical role in GBM tumorigenesis. In this study, we show that CRISPR/Cas9-mediated deletion of STAT3 in an established GBM cell line markedly inhibited tumorigenesis by intracranial injection but had little effect on cell proliferation in vitro ...
April 24, 2018: Oncotarget
Patricia Dauer, Nikita S Sharma, Vineet K Gupta, Alice Nomura, Vikas Dudeja, Ashok Saluja, Sulagna Banerjee
Chemoresistance is a major therapeutic challenge that plays a role in the poor statistical outcomes in pancreatic cancer. Unfolded Protein Response or UPR is one of the homeostasis mechanisms in cancer cells that have been correlated with chemoresistance in a number of cancers including pancreatic cancer. In the current study, we show that modulating glucose regulatory protein 78 (GRP78), the master regulator of the UPR, can have a profound effect on multiple pathways that mediate chemoresistance. Our study showed for the first time that silencing GRP78 can diminish efflux activity of ATP-binding cassette (ABC) transporters, and it can decrease the antioxidant response resulting in an accumulation of reactive oxygen species (ROS)...
May 8, 2018: Molecular Oncology
Jeffery Ho, Xianchun Li, Lin Zhang, Yonghao Liang, Wei Hu, Johnny C W Yau, Hung Chan, Tony Gin, Matthew T V Chan, Gary Tse, William K K Wu
Malignancy of the pancreas is a leading cause of cancer-related mortality, with the highest case-fatality of all cancers. Nevertheless, the lack of sensitive biomarkers and presence of biological heterogeneity precludes its early detection and effective treatment. The recent introduction of next-generation sequencing allows characterization of multiple driver mutations at genome- and exome-wide levels. Sequencing of DNA and RNA from circulating tumour cells has also opened an exciting era of non-invasive procedures for tumour detection and prognostication...
April 25, 2018: Seminars in Cancer Biology
Melin J Khandekar, Zofia Piotrowska, Henning Willers, Lecia V Sequist
The growth of genotype-directed targeted therapies, such as inhibitors of the epidermal growth factor receptor (EGFR), has revolutionized treatment for some patients with oncogene-addicted lung cancer. However, as systemic control for these patients has improved, brain metastases remain an important source of morbidity and mortality. Traditional treatment for brain metastases has been radiotherapy, either whole-brain radiation or stereotactic radiosurgery. The growing availability of drugs that can cross the blood-brain barrier and have activity in the central nervous system (CNS) has led to many studies investigating whether targeted therapy can be used in combination with or in lieu of radiation...
April 27, 2018: Oncologist
J Remon, Benjamin Besse
Brain metastases (BM) are common in non-small cell lung cancer patients including in molecularly selected populations, such as EGFR -mutant and ALK -rearranged tumors. They are associated with a reduced quality of life, and are commonly the first site of progression for patients receiving tyrosine kinase inhibitors (TKIs). In this review, we summarize incidence of BM and intracranial efficacy with TKI agents according to oncogene driver mutations, focusing on important clinical issues, notably optimal first-line treatment in oncogene-addicted lung tumors with upfront BM (local therapies followed by TKI vs...
2018: Frontiers in Oncology
Patricia Reyes-Uribe, Maria Paz Adrianzen-Ruesta, Zhong Deng, Ileabett Echevarria-Vargas, Ilgen Mender, Steven Saheb, Qin Liu, Dario C Altieri, Maureen E Murphy, Jerry W Shay, Paul M Lieberman, Jessie Villanueva
Targeting RAS is one of the greatest challenges in cancer therapy. Oncogenic mutations in NRAS are present in over 25% of melanomas and patients whose tumors harbor NRAS mutations have limited therapeutic options and poor prognosis. Thus far, there are no clinical agents available to effectively target NRAS or any other RAS oncogene. An alternative approach is to identify and target critical tumor vulnerabilities or non-oncogene addictions that are essential for tumor survival. We investigated the consequences of NRAS blockade in NRAS-mutant melanoma and show that decreased expression of the telomerase catalytic subunit, TERT, is a major consequence...
April 26, 2018: Oncogene
Michael R McDevitt, Daniel L J Thorek, Takeshi Hashimoto, Tatsuo Gondo, Darren R Veach, Sai Kiran Sharma, Teja Muralidhar Kalidindi, Diane S Abou, Philip A Watson, Bradley J Beattie, Oskar Vilhemsson Timmermand, Sven-Erik Strand, Jason S Lewis, Peter T Scardino, Howard I Scher, Hans Lilja, Steven M Larson, David Ulmert
Human kallikrein peptidase 2 (hK2) is a prostate specific enzyme whose expression is governed by the androgen receptor (AR). AR is the central oncogenic driver of prostate cancer (PCa) and is also a key regulator of DNA repair in cancer. We report an innovative therapeutic strategy that exploits the hormone-DNA repair circuit to enable molecularly-specific alpha particle irradiation of PCa. Alpha-particle irradiation of PCa is prompted by molecularly specific-targeting and internalization of the humanized monoclonal antibody hu11B6 targeting hK2 and further accelerated by inherent DNA-repair that up-regulate hK2 (KLK2) expression in vivo...
April 24, 2018: Nature Communications
Chul-Hwan Lee, Jia-Ray Yu, Sunil Kumar, Ying Jin, Gary LeRoy, Natarajan Bhanu, Syuzo Kaneko, Benjamin A Garcia, Andrew D Hamilton, Danny Reinberg
PRC2 is a therapeutic target for several types of cancers currently undergoing clinical trials. Its activity is regulated by a positive feedback loop whereby its terminal enzymatic product, H3K27me3, is specifically recognized and bound by an aromatic cage present in its EED subunit. The ensuing allosteric activation of the complex stimulates H3K27me3 deposition on chromatin. Here we report a stepwise feedback mechanism entailing key residues within distinctive interfacing motifs of EZH2 or EED that are found to be mutated in cancers and/or Weaver syndrome...
April 13, 2018: Molecular Cell
Paolo M Comoglio, Livio Trusolino, Carla Boccaccio
The MET oncogene encodes an unconventional receptor tyrosine kinase with pleiotropic functions: it initiates and sustains neoplastic transformation when genetically altered ('oncogene addiction') and fosters cancer cell survival and tumour dissemination when transcriptionally activated in the context of an adaptive response to adverse microenvironmental conditions ('oncogene expedience'). Moreover, MET is an intrinsic modulator of the self-renewal and clonogenic ability of cancer stem cells ('oncogene inherence')...
April 19, 2018: Nature Reviews. Cancer
John T Isaacs
Donald Straley Coffey completed his 85 year life's journey on November 9, 2017. In his wake, he left a legion of inspired and loyal students, fellows, and faculty colleagues from all over the world to carry on his passion both for life in general and his 50 year quest to conquer cancer. Early in his career, Dr. Coffey developed a series of animal models to study how androgen regulates the growth of both normal and abnormal prostatic epithelium. As part of these early studies, Dr. Coffey uncovered a paradox in that anti-androgen treatment given at the "wrong" time paradoxically enhanced, not inhibited, normal prostate growth...
2018: American Journal of Clinical and Experimental Urology
Yi Wang, Bing Xia, Yi-Zhuo Zhang
Diffuse large B-cell lymphoma (DLBCL) is biologically aggressive and most common pathological type of non-Hodgkin's lymphoma (NHL), and about one-third of these patients are refractory or relapsed ultimately. Based on the molecular heterogeneity, DLBCL can be divided into 3 main molecular subtypes: germinal center B-cell like (GCB), activated B-cell like (ABC) and primary mediastinal B-cell lymphoma (PMBL). Arising from B cells at distinct stages of differentiation, these subtypes are also diverse in mechanisms of oncogenic activation...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Reika Kawabata-Iwakawa, Masahiko Nishiyama
Comprehensive genomic and transcriptome analyses using next-generation sequencing(NGS)analysis has lead a discovery of a variety of novel driver gene mutations and new therapeutic targets for cancer patients, and has remarkably improved outcome of the patients through the development novel molecular targeting drugs. Even so, in so-called intractable or refractory cancers, those "druggable"alterations common to the diseases are rarely found due to the high diversity of the tumor. Furthermore, most of molecular target therapy is known to acquire the resistance to the drug by means of multiple factors such as up-regulation of the partially inhibited pathway, mutation of the target, activation of alternative pathways, histological translocation, and oncogene de-addiction...
March 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Giulia Santinon, Irene Brian, Arianna Pocaterra, Patrizia Romani, Elisa Franzolin, Chiara Rampazzo, Silvio Bicciato, Sirio Dupont
YAP/TAZ, downstream transducers of the Hippo pathway, are powerful regulators of cancer growth. How these factors control proliferation remains poorly defined. Here, we found that YAP/TAZ directly regulate expression of key enzymes involved in deoxynucleotide biosynthesis and maintain dNTP precursor pools in human cancer cells. Regulation of deoxynucleotide metabolism is required for YAP-induced cell growth and underlies the resistance of YAP-addicted cells to chemotherapeutics targeting dNTP synthesis. During RAS-induced senescence, YAP/TAZ bypass RAS-mediated inhibition of nucleotide metabolism and control senescence...
April 12, 2018: EMBO Journal
Nadia Senni, Mathilde Savall, David Cabrerizo Granados, Marie-Clotilde Alves-Guerra, Chiara Sartor, Isabelle Lagoutte, Angélique Gougelet, Benoit Terris, Hélène Gilgenkrantz, Christine Perret, Sabine Colnot, Pascale Bossard
OBJECTIVES: CTNNB1 -mutated hepatocellular carcinomas (HCCs) constitute a major part of human HCC and are largely inaccessible to target therapy. Yet, little is known about the metabolic reprogramming induced by β-catenin oncogenic activation in the liver. We aimed to decipher such reprogramming and assess whether it may represent a new avenue for targeted therapy of CTNNB1 -mutated HCC. DESIGN: We used mice with hepatocyte-specific oncogenic activation of β-catenin to evaluate metabolic reprogramming using metabolic fluxes on tumourous explants and primary hepatocytes...
April 12, 2018: Gut
Ke Gong, Gao Guo, David E Gerber, Boning Gao, Michael Peyton, Chun Huang, John D Minna, Kimmo J Hatanpaa, Kemp Kernstine, Ling Cai, Yang Xie, Hong Zhu, Farjana Fattah, Shanrong Zhang, Masaya Takahashi, Bipasha Mukherjee, Sandeep Burma, Jonathan Dowell, Kathryn Dao, Vassiliki A Papadimitrakopoulou, Victor Olivas, Trever G Bivona, Dawen Zhao, Amyn A Habib
Although aberrant Epidermal Growth Factor Receptor (EGFR) signaling is widespread in cancer, EGFR inhibition is effective only in a subset of NSCLC (non-small cell lung cancer) with EGFR activating mutations. A majority of NSCLCs express EGFR wild type (EGFRwt) and do not respond to EGFR inhibition. Tumor necrosis factor (TNF) is a major mediator of inflammation-induced cancer. We find that a rapid increase in TNF level is a universal adaptive response to EGFR inhibition in NSCLC regardless of EGFR status. EGFR signaling actively suppresses TNF mRNA levels by inducing expression of miR-21 resulting in decreased TNF mRNA stability...
April 3, 2018: Journal of Clinical Investigation
Amritha Nair, Hsiang-Ching Chung, Tingting Sun, Siddhartha Tyagi, Lacey E Dobrolecki, Rocio Dominguez-Vidana, Sarah J Kurley, Mayra Orellana, Alexander Renwick, David M Henke, Panagiotis Katsonis, Earlene Schmitt, Doug W Chan, Hui Li, Sufeng Mao, Ivana Petrovic, Chad J Creighton, Carolina Gutierrez, Julien Dubrulle, Fabio Stossi, Jeffrey W Tyner, Olivier Lichtarge, Charles Y Lin, Bing Zhang, Kenneth L Scott, Susan G Hilsenbeck, Jinpeng Sun, Xiao Yu, C Kent Osborne, Rachel Schiff, James G Christensen, David J Shields, Mothaffar F Rimawi, Matthew J Ellis, Chad A Shaw, Michael T Lewis, Thomas F Westbrook
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer diagnosed in more than 200,000 women each year and is recalcitrant to targeted therapies. Although TNBCs harbor multiple hyperactive receptor tyrosine kinases (RTKs), RTK inhibitors have been largely ineffective in TNBC patients thus far. We developed a broadly effective therapeutic strategy for TNBC that is based on combined inhibition of receptors that share the negative regulator PTPN12. Previously, we and others identified the tyrosine phosphatase PTPN12 as a tumor suppressor that is frequently inactivated in TNBC...
March 26, 2018: Nature Medicine
Chih-Yen Tu, Fang-Ju Cheng, Chuan-Mu Chen, Shu-Ling Wang, Yu-Chun Hsiao, Chia-Hung Chen, Te-Chun Hsia, Yu-Hao He, Bo-Wei Wang, I-Shan Hsieh, Yi-Lun Yeh, Chih-Hsin Tang, Yun-Ju Chen, Wei-Chien Huang
Cigarette smoking is one of the leading risks for lung cancer, and is associated with the insensitivity of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs). However, it remains undetermined whether and how cigarette smoke affects the therapeutic efficacy of EGFR TKIs. In this study, our data showed that chronic exposure to cigarette smoke extract (CSE) or tobacco smoke-derived carcinogen benzo[α]pyrene (B[α]P), but not NNK, reduced the sensitivity of wild-type EGFR-expressing non-small cell lung cancer (NSCLC) cells to EGFR TKIs...
March 23, 2018: Molecular Oncology
Leslie Duplaquet, Zoulika Kherrouche, Simon Baldacci, Philippe Jamme, Alexis B Cortot, Marie-Christine Copin, David Tulasne
Targeted therapies against receptor tyrosine kinases (RTKs) are currently used with success on a small proportion of patients displaying clear oncogene activation. Lung cancers with a mutated EGFR provide a good illustration. The efficacy of targeted treatments relies on oncogene addiction, a situation in which the growth or survival of the cancer cells depends on a single deregulated oncogene. MET, a member of the RTK family, is a promising target because it displays many deregulations in a broad panel of cancers...
March 19, 2018: Oncogene
Stephen Safe, James L Abbruzzese, Maen Abdelrahim, Erik Hedrick
Specificity protein (Sp) transcription factors (TFs) such as Sp1 are critical for early development but their expression decreases with age and there is evidence that transformation of normal cells to cancer cells is associated with upregulation of Sp1, Sp3 and Sp4 which are highly expressed in cancer cells and tumors. Sp1 is a negative prognostic factor for pancreatic, colon, glioma, gastric, breast, prostate, and lung cancer patients. Functional studies also demonstrate that Sp TFs regulate genes responsible for cancer cell growth, survival, migration/invasion, inflammation and drug resistance, and Sp1, Sp3 and Sp4 are also non-oncogene addiction (NOA) genes and important drug targets...
March 15, 2018: Cancer Prevention Research
Peiye Shen, Ying Jing, Ruiyun Zhang, Mei-Chun Cai, Pengfei Ma, Haige Chen, Guanglei Zhuang
Neuroendocrine bladder cancer is a relatively rare but often lethal malignancy, with cell of origin, oncogenomic architecture and standard treatment poorly defined. Here we performed comprehensive whole-genome and transcriptome sequencing on a unique cohort of genitourinary neuroendocrine neoplasms, mainly small cell carcinomas of the urinary bladder. The mutational landscape and signatures of neuroendocrine bladder cancer strikingly resembled those in conventional urothelial carcinoma, along with typically mixed histologies, supporting a common cellular origin...
March 14, 2018: Oncogene
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"