Have molecular hybrids delivered effective anti-cancer treatments and what should future drug discovery focus on?

Cancer continues to be a big threat and its treatment is a huge challenge among the medical fraternity. Conventional anti-cancer agents are losing their efficiency which highlights the need to introduce new anti-cancer entities for treating this complex disease. A hybrid molecule has a tendency to act through varied modes of action on multiple targets at a given time. Thus, there is the significant scope with hybrid compounds to tackle the existing limitations of cancer chemotherapy.This perspective describes the most significant hybrids that spring hope in the field of cancer chemotherapy. Several hybrids with anti-proliferative/anti-tumor properties currently approved or in clinical development are outlined, along with a description of their mechanism of action and identified drug targets.The success of molecular hybridization in cancer chemotherapy is quite evident by the number of molecules entering into clinical trials and/or have entered the drug market over the past decade. Indeed, the recent advancements and co-ordinations in the interface between chemistry, biology, and pharmacology will help further the advancement of hybrid chemotherapeutics in the future.List of abbreviations: Deoxyribonucleic acid, DNA; national cancer institute, NCI; peripheral blood mononuclear cells, PBMC; food and drug administration, FDA; histone deacetylase, HDAC; epidermal growth factor receptor, EGFR; vascular endothelial growth factor receptor, VEGFR; suberoylanilide hydroxamic acid, SAHA; farnesyltransferase inhibitor, FTI; adenosine triphosphate, ATP; Tamoxifen, TAM; selective estrogen receptor modulator, SERM; structure activity relationship, SAR; estrogen receptor, ER; lethal dose, LD; half maximal growth inhibitory concentration, GI50; half maximal inhibitory concentration, IC50.