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Molecular pathways: comparing the effects of drugs and T cells to effectively target oncogenes

Item Type:Article
Title:Molecular pathways: comparing the effects of drugs and T cells to effectively target oncogenes
Creators Name:Anders, K. and Blankenstein, T.
Abstract:Mutant cancer-driving oncogenes are the best therapeutic targets, both with drugs like small molecule inhibitors (SMI) and adoptive T cell therapy (ATT), the most effective form of immunotherapy. Cancer cell survival often depends on oncogenes, which implies that they are homogenously expressed by all cancer cells and are difficult to select against. Mutant oncogene-directed therapy is relative selective, since it targets preferentially the oncogene expressing cancer cells. Both, SMI and ATT can be highly effective in relevant preclinical models as well as selected clinical situations and both share the risk of therapy resistance, facilitated by the frequent genetic instability of cancer cells. Recently, both therapies were compared in the same experimental model targeting the same oncogene. It showed that the oncogene-inactivating drug selected resistant clones, leading eventually to tumor relapse, while ATT eradicated large established tumors completely. The mode of tumor destruction likely explained the different outcome with only ATT destroying the tumor vasculature. Elucidating the cellular and molecular mechanisms responsible for tumor regression and relapse will define optimal conditions for the clinic. We argue that the ideal conditions of ATT in the experimental cancer model can be translated to individuals with cancer.
Keywords:Genomic Instability, Drug Resistance, T Cell Therapy, Tumor Stroma, Tumor Burden, Animals, Mice
Source:Clinical Cancer Research
Publisher:American Association for Cancer Research
Page Range:320-326
Date:15 January 2013
Official Publication:https://doi.org/10.1158/1078-0432.CCR-12-3017
PubMed:View item in PubMed

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