title: Serendipity in Cancer Drug Discovery: Rational or Coincidence?
abstract: Novel drug development leading to final approval by the US FDA can cost as much as two billion dollars. Why the cost of novel drug discovery is so expensive is unclear, but high failure rates at the preclinical and clinical stages are major reasons. Although therapies targeting a given cell signaling pathway or a protein have become prominent in drug discovery, such treatments have done little in preventing or treating any disease alone because most chronic diseases have been found to be multigenic. A review of the discovery of numerous drugs currently being used for various diseases including cancer, diabetes, cardiovascular, pulmonary, and autoimmune diseases indicates that serendipity has played a major role in the discovery. In this review we provide evidence that rational drug discovery and targeted therapies have minimal roles in drug discovery, and that serendipity and coincidence have played and continue to play major roles. The primary focus in this review is on cancer-related drug discovery.
authors.affiliation: Cytokine Research Laboratory, Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Sahdeo
authors.initials: S
authors.lastname: Prasad
authors.affiliation: Department of Biochemistry, Institute of Science, Banaras Hindu University, 221005 India.
authors.forename: Subash C
authors.initials: SC
authors.lastname: Gupta
authors.affiliation: Cytokine Research Laboratory, Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: bbaggarwal@gmail.com.
authors.forename: Bharat B
authors.initials: BB
authors.lastname: Aggarwal
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017277:Drug Approval; D015195:Drug Design; D055808:Drug Discovery / Q000191:economics / Q000379:methods*; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents
keywords: chronic diseases; multitargeted; natural sources