Accelerating cancer therapy development: the importance of combination strategies and collaboration. Summary of an Institute of Medicine workshop.
Cancer cells contain multiple genetic changes in cell signaling pathways that drive abnormal cell survival, proliferation, invasion, and metastasis. Unfortunately, patients treated with single agents inhibiting only one of these pathways--even if showing an initial response--often develop resistance with subsequent relapse or progression of their cancer, typically via the activation of an alternative uninhibited pathway. Combination therapies offer the potential for inhibiting multiple targets and pathways simultaneously to more effectively kill cancer cells and prevent or delay the emergence of drug resistance. However, there are many unique challenges to developing combination therapies, including devising and applying appropriate preclinical tests and clinical trial designs, prioritizing which combination therapies to test, avoiding overlapping toxicity of multiple agents, and overcoming legal, cultural, and regulatory barriers that impede collaboration among multiple companies, organizations, and/or institutions. More effective strategies to efficiently develop combination cancer therapies are urgently needed. Thus, the Institute of Medicine's National Cancer Policy Forum recently convened a workshop with the goal of identifying barriers that may be impeding the development of combination investigational cancer therapies, as well as potential solutions to overcome those barriers, improve collaboration, and ultimately accelerate the development of promising combinations of investigational cancer therapies.
Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48201, USA. lorussop@karmanos.org
Patricia M
PM
LoRusso
Renzo
R
Canetta
John A
JA
Wagner
Erin P
EP
Balogh
Sharyl J
SJ
Nass
Scott A
SA
Boerner
John
J
Hohneker
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D003299:Cooperative Behavior; D055808:Drug Discovery / Q000331:legislation & jurisprudence; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D033183:Interdisciplinary Communication; D015969:National Academies of Science, Engineering, and Medicine, U.S., Health and Medicine Division; D009369:Neoplasms / Q000628:therapy*; D014481:United States