Malaria driven mechanisms shaping cancer risk and aggressiveness in African populations.

Malaria and cancer represent intersecting public health challenges in sub-Saharan Africa, where malaria remains endemic and cancer incidence is rapidly increasing. Emerging evidence indicates that chronic or recurrent malaria infection may influence carcinogenesis and tumour aggressiveness through complex biological mechanisms. This narrative review critically synthesizes data from PubMed, Scopus, and Web of Science to elucidate the mechanistic intersections between malaria and cancer risk, progression, and therapeutic response. The review highlights five principal axes linking malaria to oncogenesis: malaria-induced oxidative stress and chronic inflammation driving genomic instability; gut microbiome dysbiosis altering systemic immunity and tumour microenvironment; exploitation of shared molecular targets such as the endothelial protein C receptor (EPCR) and oncofetal chondroitin sulfate by Plasmodium parasites and cancer cells; cooperative interactions between malaria and oncogenic viruses like Epstein-Barr virus in lymphomagenesis; and malaria-associated vitamin D deficiency impairing immune surveillance. Furthermore, pharmacological evidence reveals that several antimalarial agents, including artemisinin derivatives, chloroquine, and quinacrine, possess anticancer properties, while some anticancer drugs exhibit antimalarial activity, underscoring opportunities for dual-action or repurposed therapeutics. The convergence of malaria and cancer biology underscores the urgent need for integrative, multidisciplinary research spanning molecular epidemiology, immunology, and pharmacology. Unveiling these mechanisms may unveil novel biomarkers and therapeutic targets, guiding context-specific interventions to reduce the disproportionate cancer burden in malaria-endemic African populations.