Dr Braun on Future Directions for Research Into Protein Glycosylation in RCC

“We’ve done a lot of genomics as a field in transcriptomics but not a lot with protein glycosylation. Is this something that’s worth studying? I think the answer is yes.”

David A. Braun, MD, PhD, assistant professor, medical oncology, Louis Goodman and Alfred Gilman Yale Scholar, member, Center of Molecular and Cellular Oncology, Yale Cancer Center, discusses future directions for research into protein glycosylation as a biomarker of response in renal cell carcinoma (RCC).

Although advancements in genomics and transcriptomics have enhanced understanding of cancer biology, protein glycosylation, a post-translational modification of proteins, remains an underexplored area in RCC despite its known role in the malignancy, Braun begins. Altered glycosylation is a hallmark of cancer, influencing tumor progression, immune modulation, and potentially resistance to immune checkpoint inhibitors, Braun adds, stating that this makes it an area worthy of further investigation.

Early, hypothesis-generating data indicate that specific glycopeptides may serve as prognostic or predictive biomarkers for response to immunotherapy, Braun continues. For instance, sialylation, a type of glycosylation, has been linked to immune suppression and reduced efficacy of immune checkpoint blockade, he states. However, the current data are preliminary, and validation in additional cohorts treated with similar immunotherapy regimens is essential, according to Braun. Demonstrating consistent alterations in glycopeptides across patient populations would confirm their prognostic or predictive value and pave the way for their integration into clinical practice, Braun says. If these findings are validated, they could open new avenues for biological investigation into how altered glycosylation contributes to tumor progression and immune evasion, he emphasizes.

Understanding these mechanisms could guide the development of therapeutic interventions to modify glycosylation patterns and enhance immunotherapy efficacy, Braun states. However, these advancements are contingent on rigorous validation studies and subsequent mechanistic research, he notes. Investigating protein glycosylation represents an opportunity to address gaps in cancer biology and potentially improve the outcomes of immunotherapy-based treatments, marking it as a promising area for future research, Braun concludes.