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https://www.readbyqxmd.com/read/27845911/deciphering-the-link-between-pi3k-and-pak-an-opportunity-to-target-key-pathways-in-pancreatic-cancer
#1
REVIEW
Kiruthikah Thillai, Hoyin Lam, Debashis Sarker, Claire M Wells
The development of personalised therapies has ushered in a new and exciting era of cancer treatment for a variety of solid malignancies. Yet pancreatic ductal adenocarcinoma (PDAC) has failed to benefit from this paradigm shift, remaining notoriously refractory to targeted therapies. Chemotherapy is the cornerstone of management but can offer only modest survival benefits of a few months with 5-year survival rates rarely exceeding 3%. Despite these disappointing statistics, significant strides have been made towards understanding the complex biology of pancreatic cancer, with deep genomic sequencing identifying novel genetic aberrations and key signalling pathways...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27708512/genetic-factors-affecting-patient-responses-to-pancreatic-cancer-treatment
#2
George Fotopoulos, Konstantinos Syrigos, Muhammad Wasif Saif
Cancer of the exocrine pancreas is a malignancy with a high lethal rate. Surgical resection is the only possible curative mode of treatment. Metastatic pancreatic cancer is incurable with modest results from the current treatment options. New genomic information could prove treatment efficacy. An independent review of PubMed and ScienceDirect databases was performed up to March 2016, using combinations of terms such pancreatic exocrine cancer, chemotherapy, genomic profile, pancreatic cancer pharmacogenomics, genomics, molecular pancreatic pathogenesis, and targeted therapy...
October 2016: Annals of Gastroenterology: Quarterly Publication of the Hellenic Society of Gastroenterology
https://www.readbyqxmd.com/read/27688185/k-ras-and-its-inhibitors-towards-personalized-cancer-treatment-pharmacological-and-structural-perspectives
#3
Vivek Asati, Debarshi Kar Mahapatra, Sanjay Kumar Bharti
The discovery of genetic, genomic and clinical biomarkers have revolutionized the treatment option in the form of personalized medicine which allows to accurately predict a person's susceptibility/progression of disease, the patient's response to therapy, and maximize the therapeutic outcome in terms of low/no toxicity for a particular patient. Recently, the U.S. Food and Drug Administration has realized the contribution of pharmacogenomics in better healthcare and advocated the consideration of pharmacogenomic principles in making safer and more effective drug...
September 16, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27630273/paradoxical-role-of-hmgb1-in-pancreatic-cancer-tumor-suppressor-or-tumor-promoter
#4
REVIEW
María José García Cebrián, Monika Bauden, Roland Andersson, Stefan Holdenrieder, Daniel Ansari
Pancreatic cancer has a dismal prognosis and there is an increasing and unmet need to identify better diagnostic and therapeutic targets in order to ameliorate the course of the disease. HMGB1, a nuclear DNA-binding protein that acts as a transcription factor, is currently in the limelight. HMGB1 exhibits a dual role in pancreatic cancer; when intracellular, it acts as an anti-tumor protein stabilizing the genome, whereas extracellular HMGB1 behaves as a pro-tumor protein with cytokine, chemokine and growth factor functions...
September 2016: Anticancer Research
https://www.readbyqxmd.com/read/27621332/current-and-evolving-therapies-for-metastatic-pancreatic-cancer-are-we-stuck-with-cytotoxic-chemotherapy
#5
REVIEW
Gauri R Varadhachary, Robert A Wolff
At present, front-line therapy for metastatic pancreatic ductal adenocarcinoma is combination chemotherapy, most commonly FOLFIRINOX (fluorouracil, irinotecan, and oxaliplatin) or gemcitabine and nanoparticle albumin-bound paclitaxel. Despite a better understanding of the genomic landscape and the importance of the tumor microenvironment, we have not made a seismic shift in the overall survival for this disease. Given our growing understanding of the biology of pancreatic ductal adenocarcinoma, the question remains whether novel, noncytotoxic agents will augment or even replace conventional chemotherapy...
September 2016: Journal of Oncology Practice
https://www.readbyqxmd.com/read/27498575/advances-in-understanding-the-molecular-mechanism-of-pancreatic-cancer-metastasis
#6
Yong-Xing Du, Zi-Wen Liu, Lei You, Wen-Ming Wu, Yu-Pei Zhao
BACKGROUND: Pancreatic cancer (PC) is usually diagnosed at the late-stage and therefore, has widespread metastasis and a very high mortality rate. The mechanisms underlying PC metastasis are not well understood. Recent advances in genomic sequencing have identified groups of gene mutations that affect PC metastasis, but studies elucidating their roles are lacking. The present review was to investigate the molecular mechanisms of PC metastasis. DATA SOURCES: Relevant articles on PC metastasis were searched in MEDLINE via PubMed prior to April 2015...
August 2016: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/27444064/pancreatic-cancer-biology-and-genetics-from-an-evolutionary-perspective
#7
Alvin Makohon-Moore, Christine A Iacobuzio-Donahue
Cancer is an evolutionary disease, containing the hallmarks of an asexually reproducing unicellular organism subject to evolutionary paradigms. Pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer) is a particularly robust example of this phenomenon. Genomic features indicate that pancreatic cancer cells are selected for fitness advantages when encountering the geographic and resource-depleted constraints of the microenvironment. Phenotypic adaptations to these pressures help disseminated cells to survive in secondary sites, a major clinical problem for patients with this disease...
September 2016: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/27345450/-new-molecular-classification-of-colorectal-cancer-pancreatic-cancer-and-stomach-cancer-towards-%C3%A3-la-carte-treatment
#8
REVIEW
Chantal Dreyer, Pauline Afchain, Isabelle Trouilloud, Thierry André
This review reports 3 of recently published molecular classifications of the 3 main gastro-intestinal cancers: gastric, pancreatic and colorectal adenocarcinoma. In colorectal adenocarcinoma, 6 independent classifications were combined to finally hold 4 molecular sub-groups, Consensus Molecular Subtypes (CMS 1-4), linked to various clinical, molecular and survival data. CMS1 (14% MSI with immune activation); CMS2 (37%: canonical with epithelial differentiation and activation of the WNT/MYC pathway); CMS3 (13% metabolic with epithelial differentiation and RAS mutation); CMS4 (23%: mesenchymal with activation of TGFβ pathway and angiogenesis with stromal invasion)...
July 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/27297136/inflammation-as-a-driver-and-vulnerability-of-kras-mediated-oncogenesis
#9
REVIEW
Shunsuke Kitajima, Rohit Thummalapalli, David A Barbie
While important strides have been made in cancer therapy by targeting certain oncogenes, KRAS, the most common among them, remains refractory to this approach. In recent years, a deeper understanding of the critical importance of inflammation in promoting KRAS-driven oncogenesis has emerged, and applies across the different contexts of lung, pancreatic, and colorectal tumorigenesis. Here we review why these tissue types are particularly prone to developing KRAS mutations, and how inflammation conspires with KRAS signaling to fuel carcinogenesis...
October 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27170400/molecular-pathogenesis-and-current-therapy-in-intrahepatic-cholangiocarcinoma
#10
Dan Høgdall, Colm J O'Rourke, Andrzej Taranta, Douglas V N P Oliveira, Jesper B Andersen
Intrahepatic cholangiocarcinoma (iCCA) comprises one of the most rapidly evolving cancer types. An underlying chronic inflammatory liver disease that precedes liver cancer development for several decades and creates a pro-oncogenic microenvironment frequently impairs progress in therapeutic approaches. Depending on the cellular target of malignant transformation, a large spectrum of molecular and morphological patterns is observed. As such, it is crucial to advance our existing understanding of the molecular pathogenesis of iCCA, particularly its genomic heterogeneity, to improve current clinical strategies and patient outcome...
2016: Digestive Diseases
https://www.readbyqxmd.com/read/27067725/understanding-the-cellular-roles-of-fyn-related-kinase-frk-implications-in-cancer-biology
#11
Raghuveera Kumar Goel, Kiven Erique Lukong
The non-receptor tyrosine kinase Fyn-related kinase (FRK) is a member of the BRK family kinases (BFKs) and is distantly related to the Src family kinases (SFKs). FRK was first discovered in 1993, and studies pursued thereafter attributed a potential tumour-suppressive function to the enzyme. In recent years, however, further functional characterization of the tyrosine kinase in diverse cancer types suggests that FRK may potentially play an oncogenic role as well. Specifically, while ectopic expression of FRK suppresses cell proliferation and migration in breast and brain cancers, knockdown or catalytic inhibition of FRK suppresses these cellular processes in pancreatic and liver cancer...
June 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27041411/genetic-testing-in-pancreatic-ductal-adenocarcinoma-implications-for-prevention-and-treatment
#12
REVIEW
Mary Linton B Peters, Jennifer F Tseng, Rebecca A Miksad
PURPOSE: This article reviews the progress to date and future directions for investigation of germline and somatic genetic testing to inform pancreatic adenocarcinoma (PDAC) treatment, screening, and prevention strategies. METHODS: We searched PubMed to identify recent articles regarding genetic testing in pancreatic cancer, including both germline and somatic testing, and recent genome-wide association studies. References were specifically hand searched as relevant...
July 2016: Clinical Therapeutics
https://www.readbyqxmd.com/read/27039259/tgf-%C3%AE-signaling-in-liver-and-gastrointestinal-cancers
#13
L H Katz, M Likhter, W Jogunoori, M Belkin, K Ohshiro, L Mishra
Transforming Growth Factor-β (TGF-β) plays crucial and complex roles in liver and gastrointestinal cancers. These include a multitude of distinct functions, such as maintaining stem cell homeostasis, promoting fibrosis, immune modulating, as a tumor suppressor and paradoxically, as a tumor progressor. However, key mechanisms for the switches responsible for these distinct actions are poorly understood, and remain a challenge. The Cancer Genome Atlas (TCGA) analyses and genetically engineered mouse models now provide an integrated approach to dissect these multifaceted and context-dependent driving roles of the TGF-β pathway...
September 1, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27013361/molecular-and-genetic-basis-of-pancreatic-carcinogenesis-which-concepts-may-be-clinically-relevant
#14
REVIEW
Vincent Bernard, Jason Fleming, Anirban Maitra
Carcinogenic progression in the pancreas arises through a well-established stepwise accumulation of molecular aberrations from a normal cell to an invasive adenocarcinoma. Recent large-scale sequencing efforts have provided insight into novel driver genes as well as enriched core signaling pathways that underlie the inherent heterogeneity found in pancreatic cancer. By exploiting these genomic profiles, we may begin to provide new insights into patient stratification and therapeutic guidance. This review discusses the molecular landscape of pancreatic cancer and its role in tumor progression, clinical prognostication, and the development of novel therapeutic strategies...
April 2016: Surgical Oncology Clinics of North America
https://www.readbyqxmd.com/read/26929738/pancreatic-cancer-genetics
#15
REVIEW
Laufey T Amundadottir
Although relatively rare, pancreatic tumors are highly lethal [1]. In the United States, an estimated 48,960 individuals will be diagnosed with pancreatic cancer and 40,560 will die from this disease in 2015 [1]. Globally, 337,872 new pancreatic cancer cases and 330,391 deaths were estimated in 2012 [2]. In contrast to most other cancers, mortality rates for pancreatic cancer are not improving; in the US, it is predicted to become the second leading cause of cancer related deaths by 2030 [3, 4]. The vast majority of tumors arise in the exocrine pancreas, with pancreatic ductal adenocarcinoma (PDAC) accounting for approximately 95% of tumors...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/26881472/genomic-instability-in-pancreatic-adenocarcinoma-a-new-step-towards-precision-medicine-and-novel-therapeutic-approaches
#16
Ibrahim H Sahin, Maeve A Lowery, Zsofia K Stadler, Erin Salo-Mullen, Christine A Iacobuzio-Donahue, David P Kelsen, Eileen M O'Reilly
Pancreatic cancer is one of the most challenging cancers. Whole genome sequencing studies have been conducted to elucidate the underlying fundamentals underscoring disease behavior. Studies have identified a subgroup of pancreatic cancer patients with distinct molecular and clinical features. Genetic fingerprinting of these tumors is consistent with an unstable genome and defective DNA repair pathways, which creates unique susceptibility to agents inducing DNA damage. BRCA1/2 mutations, both germline and somatic, which lead to impaired DNA repair, are found to be important biomarkers of genomic instability as well as of response to DNA damaging agents...
August 2016: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/26781267/clinical-aspects-and-perspectives-of-erlotinib-in-the-treatment-of-patients-with-biliary-tract-cancer
#17
REVIEW
Lars Henrik Jensen
INTRODUCTION: Patients with non-resectable biliary tract cancer have a poor prognosis even if treated with systemic chemotherapy. One hope for improving treatment is through molecular biology and the characterization of specific cancer driving alterations followed by the design of targeted drugs. The epidermal growth factor receptor system is upregulated in many cancers and can be targeted by the protein kinase inhibitor erlotinib. Erlotinib has demonstrated a clinically applicable effect in pancreatic and lung cancer Areas covered: In this review, the author presents the published clinical data about erlotinib in biliary tract cancer...
2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/26730578/epidemiologic-studies-of-the-human-microbiome-and-cancer
#18
Emily Vogtmann, James J Goedert
The human microbiome, which includes the collective genome of all bacteria, archaea, fungi, protists, and viruses found in and on the human body, is altered in many diseases and may substantially affect cancer risk. Previously detected associations of individual bacteria (e.g., Helicobacter pylori), periodontal disease, and inflammation with specific cancers have motivated studies considering the association between the human microbiome and cancer risk. This short review summarises microbiome research, focusing on published epidemiological associations with gastric, oesophageal, hepatobiliary, pancreatic, lung, colorectal, and other cancers...
February 2, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/26652651/pathobiology-of-pancreatic-cancer-implications-on-therapy
#19
REVIEW
Ivonne Regel, Simone Hausmann, Simone Benitz, Irene Esposito, Jörg Kleeff
Although the concept of tumor heterogeneity was established several decades ago, the interest in this topic is still unbroken. With the identification of inter- and intratumoral genomic rearrangements and the detection of cancer stem cells (CSCs) through phenotypic variations of cancer cells there are increasing options for pancreatic cancer therapy. Indeed, some pre-clinical studies have shown promising results in the treatment of drug-resistant CSCs, whereby a few strategies were already tested in clinical trials...
2016: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/26646652/pancreatic-neuroendocrine-neoplasms-clinical-value-of-diffusion-weighted-imaging
#20
Riccardo De Robertis, Mirko D'Onofrio, Giulia Zamboni, Paolo Tinazzi Martini, Stefano Gobbo, Paola Capelli, Giovanni Butturini, Roberto Girelli, Silvia Ortolani, Sara Cingarlini, Paolo Pederzoli, Aldo Scarpa
BACKGROUND/AIMS: Diffusion-weighted imaging (DWI) can depict random motions of water molecules in biological tissues during magnetic resonance (MR) examinations. Few papers have tested its application to pancreatic neuroendocrine neoplasms (PanNENs). The aim of this paper is to assess the clinical value of DWI regarding the identification and characterization of PanNENs and diagnosis of liver metastases. METHODS: Preoperative MR examinations of 30 PanNEN patients were retrospectively reviewed; 30 patients with pathologically proven pancreatic ductal adenocarcinoma (PDAC) were included to compare the imaging features...
2016: Neuroendocrinology
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