A single-cell lens into the co-evolution of genotypes and phenotypes in cancer

A new review by Izzo et al. in Nature Reviews Cancer synthesizes how single-cell multimodal sequencing enables direct mapping of genotype to phenotype in cancer, revealing mutant-specific vulnerabilities exploitable for therapy. By combining multi-omic profiling with phylogenetic reconstruction, the authors outline a framework for tracking clonal evolution and cell-state plasticity across pre-malignant and malignant tissues. The work highlights how these approaches can identify targetable dependencies tied to specific somatic mutations and inform precision oncology strategies.