Résumé
Gastrointestinal (GI) malignancies accounted for more than one in four cancer cases (4.8 million cases) in 2020. Among these, around 37% were colorectal followed by gastric (21%) and liver cancers (18%). Notably, GI cancers are responsible for nearly one-third of cancer-related mortality (3.4 million deaths worldwide). For decades, treatment relied primarily on conventional cytotoxic chemotherapies, which target rapidly dividing malignant cells but also cause significant harm to healthy tissue. Recent biotechnological advances enhanced our understanding of cancer biology, leading to the identification of specific molecular alterations and the development of new drugs, known as "targeted therapies." These therapies include two major categories: small molecule kinase inhibitors (SMKIs), which inhibit dysregulated intracellular kinases, and monoclonal antibodies (mAbs), able to interfere with extracellular ligands, membrane receptors, or membrane-bound proteins.
This review aims to summarize recent advancements in the treatment of GI cancers using mAbs. We provide an overview of clinically approved mAbs in GI cancers, detailing their targets, mechanisms of action, and limitations. We differentiate between mAbs that directly target cancer cells and those that act on the tumor microenvironment (TME). Additionally, we discuss developments and technological optimizations used to improve the efficacy and specificity of these therapies.
[Display omitted] Different strategies utilizing monoclonal antibodies (mAbs) are currently employed in the clinical management of gastrointestinal (GI) cancers. mAbs can target tumor-associated antigens (TAAs) expressed on cancer cells, exerting anti-tumor effects either via the engagement of immune effector mechanisms, or by serving as carriers for cytotoxic agents to enable targeted drug delivery. Other mAbs act on components of the tumor microenvironment (TME), either by blocking immune checkpoints to restore T cell function or by neutralizing pro-tumorigenic signaling molecules that support tumor growth and survival. Currently, mAbs directed against seven key targets—epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), Claudin 18.2 (CLDN18.2), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)—have been approved for the treatment of GI malignancies.