title: Opportunities and challenges in the development of experimental drug combinations for cancer.
abstract: It is becoming increasingly evident that cancers are dependent on a number of altered molecular pathways and can develop diverse mechanisms of resistance to therapy with single agents. Therefore, combination regimens may provide the best hope for effective therapies with durable effects. Despite preclinical data to support this notion, there are many challenges to the development of targeted combinations including scientific, economic, legal, and regulatory barriers. A discussion of these challenges and identification of models and best practices are presented with intent of aiding the research community in addressing real and perceived barriers to the development of combination therapies for cancer.
authors.affiliation: Global Development, Bristol-Myers Squibb Company, Princeton, NJ, USA.
authors.forename: Rachel W
authors.initials: RW
authors.lastname: Humphrey
authors.forename: Laura M
authors.initials: LM
authors.lastname: Brockway-Lunardi
authors.forename: David T
authors.initials: DT
authors.lastname: Bonk
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Dohoney
authors.forename: James H
authors.initials: JH
authors.lastname: Doroshow
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Meech
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Ratain
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Topalian
authors.forename: Drew M
authors.initials: DM
authors.lastname: Pardoll
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects* / Q000494:pharmacology; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic / Q000379:methods* / Q000592:standards / Q000639:trends; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004345:Drug Industry / Q000331:legislation & jurisprudence; D004357:Drug Synergism; D006801:Humans; D018973:Intellectual Property; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends; D054547:National Cancer Institute (U.S.); D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D012107:Research Design; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents