Screening of Anticancer Drugs

Introduction & rationale

• Definition — Screening of anticancer drugs is the systematic, tiered preclinical testing of candidate compounds for antitumour / antiproliferative activity using in-vitro (cell-based) and in-vivo (animal) models, to identify and prioritise molecules before clinical trials.
• Driving need — Cancer is a leading cause of death worldwide; >100 cancer types; a multifactorial disease driven by activation of proto-oncogenes + inhibition of tumour-suppressor genes and angiogenesis (VEGF). Existing cytotoxics are highly toxic and costly, driving the search for rapid, novel screens.
• Sources — Anticancer agents come from natural products (plants, microbes) and synthetic molecules; oncology is the third-largest therapeutic market after CNS and cardiovascular drugs.
• Tiered cascade — Large compound libraries → primary in-vitro cytotoxicity screen (rapid, cheap, high-throughput) → secondary in-vivo confirmation (host-mediated activity, therapeutic ratio) → most promising candidate tested in >1 animal model → clinical development.
• Resistance built in — Treatment failure in advanced cancer arises from misdiagnosis or development of resistance; drug-resistant tumours are deliberately incorporated into screening panels to flag agents active against resistant disease.