Targeted Therapy and Personalized Treatment Approaches

Cancer therapy is shifting from “one-size-fits-all” to precision oncology, a regime that precisely analyzes and targets distinct molecular wiring in individual clinical tumors. This chapter discusses this strategic shift where clinical and multi-omics data reveal the key hallmarks and drivers of cancer, enabling treatments lethal to the tumor, not the patient, and thereby aiding efficacy while avoiding harm to healthy tissue. It further maps the key therapeutic axes including RTKs (EGFR/HER2/FGFR/VEGFR), oncogenic gene fusions and MAPK/PI3K, epigenetic players, and immune checkpoints, to show how their targeting can be translated into drugs to produce durable responses. Beyond the singular marker approach, this chapter highlights the utility of integrated profiling (genomic, proteomic, and metabolomic) and new age tools including CRISPR screens, single-cell/spatial omics, and machine learning to analyze, validate, and target the tumor vulnerabilities. The approval of landmark clinical precision therapeutics and tissue-agnostic approaches is reviewed further to elucidate the success of precision oncology in clinical and translation settings. Realizing the risk of primary and acquired resistance, recognized as a central challenge linked with tumor evolution emerging from on-target mutations, bypass signaling, and clonal heterogeneity, utility of novel strategies including next-gen inhibitors, rational combinations, and adaptive/sequential treatment guided by real-time liquid biopsy was comprehensively reviewed. In the chapter, we further argued that multi-omics convergence with explainable machine learning could help in resolving the therapeutic resistance in the tumors and predicting the drug combinations that could enable their effective clinical management.