Curtailing the high rate of late-stage attrition of investigational therapeutics against unprecedented targets in patients with lung and other malignancies

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Eric Rowinsky

Abstract

A greater understanding of the pathogenesis and biology of cancer coupled with major advances in biotechnology has resulted in the identification of rationally designed, target-based (RDTB) anticancer therapeutics, ushering in new therapeutic opportunities and high expectations for the future as well as developmental challenges. Because these agents appear to principally target malignant cells, it is expected that they will produce less toxicity at clinically effective doses than nonspecific cytotoxic agents, but their target requirements are likely to be much more stringent. The innate complexity of the networks that contain elements targeted by these agents also decreases the probability that any single therapeutic manipulation will result in robust clinical activity and success when used alone, particularly in patients with solid malignancies that have multiple relevant signaling aberrations. In contrast, proof of principle and robust antitumor activity may be most efficiently demonstrated in nonrandomized evaluations involving tumors that are principally driven by aberrations of the specific target. The predominant therapeutic manifestation of RDTB agents in preclinical studies is due to decreased tumor growth rates and wil...Continue Reading

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Citations

Apr 27, 2010·Analytical and Bioanalytical Chemistry·Donald Wlodkowic, Jonathan M Cooper
Nov 8, 2008·Nature Reviews. Drug Discovery·Avi Ashkenazi
May 24, 2011·World Journal of Clinical Oncology·Donald Wlodkowic, Zbigniew Darzynkiewicz
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Oct 20, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Heinz-Josef LenzEric K Rowinsky
Jun 14, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eric K Rowinsky
Jan 1, 2005·Current Opinion in Oncology·Eric K Rowinsky
Aug 6, 2019·Stem Cells·Sanam L Kavari, Khalid Shah
Mar 4, 2011·Clinical Pharmacology and Therapeutics·A D Ricart

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