Cancers, Vol. 10, Pages 142: A New Strategy to Control and Eradicate “Undruggable” Oncogenic K-RAS-Driven Pancreatic Cancer: Molecular Insights and Core Principles Learned from Developmental and Evolutionary Biology

Cancers, Vol. 10, Pages 142: A New Strategy to Control and Eradicate “Undruggable” Oncogenic K-RAS-Driven Pancreatic Cancer: Molecular Insights and Core Principles Learned from Developmental and Evolutionary Biology Cancers doi: 10.3390/cancers10050142 Authors: Robert Van Sciver Michael Lee Caroline Lee Alex Lafever Elizaveta Svyatova Kevin Kanda Amber Colliver Lauren Siewertsz van Reesema Angela Tang-Tan Vasilena Zheleva Monicah Bwayi Minglei Bian Rebecca Schmidt Lynn Matrisian Gloria Petersen Amy Tang Oncogenic K-RAS mutations are found in virtually all pancreatic cancers, making K-RAS one of the most targeted oncoproteins for drug development in cancer therapies. Despite intense research efforts over the past three decades, oncogenic K-RAS has remained largely “undruggable”. Rather than targeting an upstream component of the RAS signaling pathway (i.e., EGFR/HER2) and/or the midstream effector kinases (i.e., RAF/MEK/ERK/PI3K/mTOR), we propose an alternative strategy to control oncogenic K-RAS signal by targeting its most downstream signaling module, Seven-In-Absentia Homolog (SIAH). SIAH E3 ligase controls the signal output of oncogenic K-RAS hyperactivation that drives unchecked cell proliferation, uncontrolled tumor growth, and rapid cancer cell dissemination in human pancreatic cancer. Therefore, SIAH is an ideal therapeutic target as it is an extraordinarily conserved downstream signaling gatekeeper indispensable for proper...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research