From Combination Early Detection to Multicancer Testing: Shifting Cancer Care toward Proactive Prevention and...

Identifying the presence of tumors at a very early stage or deciphering the processes underlying their development can enable the interception of promalignant mechanisms underpinning cancer emergence, facilitating more effective prevention. Advances in molecular profiling allow the detection of genetic, epigenetic, immune, and microenvironmental alterations associated with cancer risk. Liquid biopsy permits noninvasive analysis of circulating tumor cells, nucleic acids, immune cells, extracellular vesicles, proteins, cytokines, and metabolites, whereas metagenome analysis facilitates gut microbiota profiling. Multicancer early detection assays broaden this approach, capturing signals from multiple malignancies using a single blood sample. These technologies go beyond genomics, addressing immune dysregulation and metabolic shifts, and may help identify gut microbiota imbalances. Clonal hematopoiesis of indeterminate potential is gaining increasing recognition as a biomarker. Cardiovascular risk scores based on multiple parameters are an inspiring example. The analysis of a combination of cancer drivers and enablers should provide a more sensitive and personalized measure of cancer prodromic profiles. Artificial intelligence will further support this transition by integrating molecular, immune, and metabolic data to develop individualized risk profiles. This shift from single-cancer detection to integrated, mechanism-based screening fosters a more proactive prevention model. This combination of early detection empowers cancer interception by using strategies, including lifestyle modification, nutritional optimization, drug repurposing, pharmacologic interventions, and targeted chemoprevention. Moving beyond single parameters analysis and organ-specific screening, this multidimensional approach advances early detection and interception as practical clinical goals, facilitating the fundamental aim of positioning prevention at the forefront of oncology.