Signal transduction in cancer: a cross-talk

Introduction: Aberrant signal transduction is a defining feature of cancer, governing proliferation, survival, stemness, immune evasion, and therapeutic resistance. The MAPK, PI3K/AKT/mTOR, and Wnt/β-catenin pathways are frequently altered in solid tumors and function as key regulatory hubs within an interconnected signaling network. Methods: We conducted a comprehensive literature review focused on the structure, activation mechanisms, oncogenic alterations, and interactions among MAPK, PI3K/AKT/mTOR, and Wnt/β-catenin pathways. We analyzed preclinical and clinical data on therapeutic strategies targeting these pathways and examined specific implementation challenges in Latin America. Results: MAPK signaling is frequently dysregulated through RAS and BRAF mutations, promoting uncontrolled proliferation. PI3K/AKT/mTOR alterations, including PIK3CA mutations and PTEN loss, drive growth and metabolic reprogramming. Wnt/β-catenin activation supports stemness and immune evasion, often via APC or CTNNB1 mutations. Crosstalk between these pathways amplifies oncogenic signaling and contributes to therapeutic resistance. Dual inhibition strategies show preclinical promise but are limited by toxicity and compensatory feedback. Functional biomarkers and combinatorial regimens are under investigation to overcome resistance. In Latin America, access to molecular diagnostics and targeted therapies remains limited, though efforts to expand precision oncology are underway. Conclusions: Cancer signaling is shaped by a complex, adaptive network rather than isolated pathways. Therapeutic success will depend on integrated strategies that target signaling interactions. Regional implementation requires context-specific solutions, including minimal biomarker panels, expanded diagnostics, and collaborative infrastructure.