Delay in the assessment of
tumor response to
radiotherapy continues to pose a major challenge to quality of life for patients with nonresponsive
tumors. Here, we exploited label-free Raman spectroscopic mapping to elucidate radiation-induced biomolecular changes in
tumors and uncovered latent microenvironmental differences between treatment-resistant and -sensitive
tumors. We used isogenic radiation-resistant and -sensitive A549 human
lung cancer cells and human
head and neck squamous cell carcinoma (
HNSCC) cell lines (UM-SCC-47 and UM-SCC-22B, respectively) to grow
tumor xenografts in athymic nude mice and demonstrated the molecular specificity and quantitative nature of Raman spectroscopic tissue assessments. Raman spectra obtained from untreated and treated
tumors were subjected to chemometric analysis using multivariate curve resolution-alternating least squares (MCR-ALS) and support vector machine (SVM) to quantify biomolecular differences in the tumor microenvironment. The Raman measurements revealed significant and reliable differences in
lipid and
collagen content postradiation in the tumor microenvironment, with consistently greater changes observed in the radiation-sensitive
tumors. In addition to accurately evaluating
tumor response to
therapy, the combination of Raman spectral markers potentially offers a route to predicting response in untreated
tumors prior to commencing treatment. Combined with its noninvasive nature, our findings provide a rationale for in vivo studies using Raman spectroscopy, with the ultimate goal of clinical translation for patient stratification and guiding adaptation of
radiotherapy during the course of treatment. SIGNIFICANCE: These findings highlight the sensitivity of label-free Raman spectroscopy to changes induced by
radiotherapy and indicate the potential to predict radiation resistance prior to commencing
therapy.