Monoclonal Antibodies in Cancer Therapy: Mechanisms of Action and Resistance

Abstract

Therapeutic monoclonal antibodies are now part of routine care for several cancers, yet the reasons they work in one patient and fail in another remain only partly understood. This mini review summarises, from published literature, how antibodies act on tumours and how tumours escape them. Four broad mechanisms are described: blockade of growth-factor receptor signalling, engagement of immune effector cells and complement through the Fc region, release of immune checkpoints, and interference with tumour blood supply, with a fifth route, delivery of a toxic payload, noted briefly. Resistance is then considered at three levels: the tumour cell, where antigen loss, downstream mutation and bypass signalling blunt the effect; the immune compartment, where host genetics and effector exhaustion matter; and the vasculature, where alternative pro-angiogenic routes take over. The best-documented example is the loss of benefit from EGFR-directed antibodies in colorectal tumours carrying KRAS mutations. The review is narrative, reports no new data, and does not claim a systematic search. Its main conclusion is that mechanism and resistance cannot be separated: each way an antibody works is also a way it can be bypassed, and combination design should follow from that logic. Predictive markers remain scarce, and most laboratory findings still need confirmation in patients.