Multitargeted polypharmacotherapy for cancer treatment. theoretical concepts and proposals

Area of Science:

• Oncology
• Pharmacology
• Drug Discovery

Background:

• Cancer treatment has evolved from cytotoxic chemotherapy to molecular targeted therapy.
• Current targeted therapies offer limited survival gains (median 2.8 months) and face limitations due to the complexity of cancer.
• The somatic mutation theory underpinning targeted therapy has paradoxes, necessitating exploration of novel therapeutic strategies.

Purpose of the Study:

• To review the evolution of cancer therapy from cytotoxic to targeted approaches.
• To highlight the limitations of the one-target, one-drug strategy in treating cancer as a robust system.
• To propose and advocate for a multitargeting approach using polypharmacotherapy with repurposed drugs.

Main Methods:

• Overview of historical and current cancer treatment modalities.
• Analysis of the limitations of molecular targeted therapy.
• Discussion of the rationale for multitargeted polypharmacotherapy.

Main Results:

• Molecular targeted therapy has shown modest survival benefits.
• The "one-target, one-drug" approach is insufficient for complex cancer systems.
• Repurposed drugs offer a viable strategy for multitargeted polypharmacotherapy.

Conclusions:

• Multitargeted polypharmacotherapy using repurposed drugs warrants systematic investigation in preclinical and clinical studies.
• Repurposed drugs have established safety profiles, potentially reducing risks in combination therapy.
• Future cancer research should expand beyond the current targeted therapy paradigm to explore innovative approaches like polypharmacotherapy.