Combination Drug Strategies for Targeting Specific Biochemical Pathways for Superior Therapeutic Potency

Abstract

The combination drug therapy is considered as an innovative approach in drug design to reduce the toxicity of the chemotherapeutic drugs while improving their therapeutic potency multifold. The efficacy of combination therapy relies on the combined treatments’ capacity to address multiple distinct pathways, leading to a reduction in drug resistance, drug delivery approaches, optimize the concentration of the drug at the target site, and ensure that the therapeutic drug reaches the desired site by encapsulating the drug in drug delivery vehicles such as liposome or attaching it to targeting fragments. The initial successful targeted therapy, imatinib, was identified in 1996 and gained FDA approval in 2001. Imatinib is a small molecule designed to specifically inhibit the product of the 9–22 reciprocal chromosome translocation, known as the “Philadelphia chromosome.” By binding to the ATP-binding pocket of BCR-ABL, it disrupts its kinase activity. Another intriguing approach within combination drug regimens involves “conjugation drug therapy,” entailing the direct combination of two drugs into a single drug entity or molecule. Repositioning metallodrugs has shown enhanced effectiveness when used in combination therapy, either in an additive or synergistic manner, displaying minimal toxicity and significantly reducing drug resistance.