Epigenetic markers for chemosensitivity and chemoresistance in pancreatic cancer—A review

Abstract

Adjuvant first-line gemcitabine monochemotherapy presents a standard treatment for patients with advanced pancreatic adenocarcinoma and improves overall survival in chemosensitive patients. Nonetheless, 6-month progression-free survival remains below 15%, despite interdisciplinary approaches. The success of gemcitabine treatment is disappointing and-in the absence of reliable tumor markers-challenging to quantify. Epigenetic alterations have been recently identified to take on important roles in cancer development and possibly cancer treatment. In this context, microRNAs are becoming increasingly acknowledged as useful biomarkers for classifying cancers and providing information on their chemo-and radiosensitivity. This review illustrates the potential of genetic and epigenetic markers in the prediction of chemosensitivity in pancreatic cancer patients and in the monitoring of their response rates to adjuvant therapy.

Prospective of colon cancer treatments and scope for combinatorial approach to enhanced cancer cell apoptosis

“…Emerging evidence suggests that miRNAs function as key regulators in tumor oncogenesis, progression, invasion, metastasis, and angiogenesis [76]. Highly specific alterations in miRNA expression profiles have been reported for various cancer entities that are likely to have diagnostic and prognostic value.…”

Overcoming nucleoside analog chemoresistance of pancreatic cancer: A therapeutic challenge

“…The development of curcumin as a potential therapeutic for pancreatic cancer patients has been under investigation due to its interactions with DNA methyltransferase, HDACs, and HATs and ability to alter miRNA expression, including upregulation of miR-200 and downregulation of miR-21 [133]. In this regard, several recent reviews identify key growth, proliferation, and differentiation (e.g., PI3K/Akt, MAPK, K-ras, STAT-3, Notch-1, Notch-2), invasion (e.g., ABCG2, cadherin, ZEB1, vimentin), and apoptosis (e.g., CDK6, p53, caspase 3) proteins altered by miRNAs [4,132,134]. Therefore, targeting miRNAs offers great promise for tackling pancreatic cancer chemoresistance and providing diagnostic and therapeutic values.…”

New Targets for Therapy in Pancreatic Cancer

“…Recently, deregulation of miRNAs expression has been correlated to diagnosis, prognosis and chemotherapy resistance of pancreatic cancer (Chakraborty et al, 2011;Dhayat et al, 2011). Among the several miRNAs reported to be up regulated in pancreatic cancer such as miR-21, miR-221/222, miR-25, miR-27a, miR-210, miR-200b, miR-148a,b, miR-196a-2, miR-155, and members of the miR-17-92 family (Chakraborty et al, 2011;Liffers et al, 2011;Nana-Sinkam & Croce, 2011;Zhang et al, 2011), the oncomiR miR-21 appears of high relevance as potential therapeutic target in pancreatic cancer, regulating proliferation, invasion, apoptosis and chemosensitivity (Ali et al, 2010;Giovannetti et al, 2010;Hwang et al, 2010;Park et al, 2009).…”