MedicalResearch.com Interview with:
Erina Vlashi, PhD
Department of Radiation Oncology
David Geffen School of Medicine at UCLA
Los Angeles, CA 90095-1714
Medical Research: What is the background for this study? What are the main findings?
Dr. Vlashi: It has been known for quite some time that head and neck squamous cell carcinomas (HNSCC) that test positive for human papilloma virus (HPV) respond to radiation therapy more favorably than HPV-negative HNSCCs. Our team reviewed a cohort of 162 patients with a head and neck squamous carcinoma diagnosis over a two-year period, and confirmed that the outcomes were correlated with the patient’s HPV status. The work that followed was prompted by a discovery we had made earlier in breast cancer suggesting that breast cancer cells that manage to survive radiation therapy have the capacity to convert into more de-differentiated, therapy-resistant cells with characteristics of cancer stem cells, and that the degree of this conversion depended on the type of breast cancer: the more aggressive types of breast cancer being more prone to the therapy-induced phenotype conversion. So, we hypothesized that this therapy-induced conversion phenomenon may especially be at play in head and neck squamous cell carcinomas given the clinical observation that HPV-positive HNSCCs respond to radiation therapy much more favorably than HPV-negative HNSCCs, despite optimum treatment modalities. And indeed, that is what we found: tumor cells derived from a panel of head and neck squamous cell carcinomas cell lines that do not respond well to radiation therapy have an enhanced ability to convert the cells that survive radiation into more aggressive cells, cancer stem-like cells that will resist the next round of radiation therapy.
Medical Research: What should clinicians and patients take away from your report?
Dr. Vlashi: While radiation therapy is an indispensable treatment modality for many cancers and often leads to cures, there are still cancers that do not respond to this mode of treatment optimally. The more we understand the reasons behind the failures, the better positioned we are to make radiation therapy even more effective. So, for the clinicians, the realization that radiation therapy plays a role in therapy-induced dedifferentiation of cancer cells adds a new dimension to the way we think about responses to radiation therapy, and brings us a step closer to being able to further enhance tumor responses to this powerful anti-cancer treatment modality.
These studies will not immediately affect the way head and neck cancer patients are treated in the clinic. However, we are performing a large-scale search for drugs that will interfere with the process of therapy-induced “conversion” of tumor cells that can be used in combination with radiation therapy in the clinic in order to significantly improve the response to radiation therapy for head and neck squamous cell carcinomas (and hopefully other cancers) that are currently not cured by radiation therapy.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Vlashi: There is still a lot of work to be done. Although we already know that this phenotype conversion is accompanied by a re-expression of “reprogramming factors” (stem cell factors that can reprogram differentiated somatic cells into an induced pluripotent stem cells, iPS), we still need to dig deeper into the mechanism by which radiation induces the re-expression of these factors, consequently promoting dedifferentiation, and counteracting the efficacy of radiation therapy. Once we better understand the key players in this therapy-induced dedifferentiation process we should be able to find ways to interfere with the crucial steps and hopefully bring such inhibitors into the clinic for combination therapy with radiation treatment.
Erina Vlashi, Allen M. Chen, Sabrina Boyrie, Garrett Yu, Andrea Nguyen, Philip A. Brower, Clayton B. Hess, Frank Pajonk. Radiation-Induced Dedifferentiation of Head and Neck Cancer Cells into Cancer Stem Cells Depends on HPV status. International Journal of Radiation Oncology*Biology*Physics, 2016; DOI:1016/j.ijrobp.2016.01.005
Erina Vlashi, PhD (2016). Radiation Converts Some Resistant Head and Neck Cancer Cells Into Aggressive Stem Cells