Raman metabolic imaging: an emerging tool for the study of drug resistance in cancer

Metabolic heterogeneity within tumors is a key driver of drug resistance, as distinct subpopulations adapt to the tumor microenvironment by exploiting specific metabolic pathways. This diversity enables certain subpopulations to evade therapeutic intervention, thereby leading to therapy failure and cancer relapse. Metabolic reprogramming exacerbates resistance by enabling cancer cells to modulate their metabolic pathways to counteract therapeutic pressures, promoting the survival of resistant subpopulations. Traditional metabolic analyses generally measure average metabolite levels across cell populations, while Raman metabolic imaging offers a more precise, subcellular perspective, enabling non-destructive and real-time monitoring of dynamic metabolic processes related to drug resistance. Our review highlights advancements in Raman spectroscopy and microscopy, and explores their applications in cancer drug resistance research. We focus on their role in revealing intratumoral metabolic heterogeneity, monitoring metabolic reprogramming in drug-resistant cells, and enabling rapid cancer drug sensitivity evaluation.