Author Interviews, Cancer Research, Radiation Therapy, Stem Cells / 11.02.2016
Radiation Converts Some Resistant Head and Neck Cancer Cells Into Aggressive Stem Cells
MedicalResearch.com Interview with:
[caption id="attachment_21484" align="alignleft" width="120"]
Dr. Erina Vlashi[/caption]
Erina Vlashi, PhD
Assistant Professor
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.
Dr. Erina Vlashi[/caption]
Erina Vlashi, PhD
Assistant Professor
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.

Dr. Movsas[/caption]
MedicalResearch.com Interview with:
Benjamin Movsas, MD
Chairman of Radiation Oncology
Henry Ford Hospital
Detroit, Michigan
Medical Research: What is the background for this study? What are the main findings?
Dr. Movsas: The background is that a recent randomized lung cancer trial (RTOG 0617) showed a lower (rather than a higher) survival among the patients who received a higher dose of radiation (RT). This unexpected finding was puzzling as there were few differences in toxicity between the radiation dose arms noted by health care providers.
The main finding of the quality of life (QOL) analysis was that there was indeed a large difference in QOL as reported by the patients themselves (with lower QOL on the high RT dose arm at 3 months). Moreover, while this study was not randomized for RT technique, about half of the patients received intensity modulated RT (IMRT), a more sophisticated approach than the alternative (3D conformal RT), which can better protect normal tissues. Despite the fact that patients with larger tumors received
Dr. Lei Xu[/caption]
MedicalResearch.com Interview with:
Lei Xu, MD, PhD
Steele Laboratory of Tumor Biology
Radiation Oncology Department
Massachusetts General Hospital
Medical Research: What is the background for this study?
Dr. Lei Xu: Neurofibromatosis 2 is characterized by benign tumors that develop throughout the nervous system. The most common site of these tumors is the eighth cranial nerve, which carries hearing and balance information from the ears to the brain. Although these vestibular schwannomas grow slowly, they usually lead to a significant or total hearing loss by young adulthood or middle age. The tumors can also press on the brain stem, leading to headaches, difficulty swallowing and other serious neurologic symptoms. While the tumors can be surgically removed or destroyed with radiation treatment, both approaches can also damage hearing.
Several previous investigations had suggested that – unlike other benign tumors – vestibular schwannomas induce the formation of new blood vessels, as malignant tumors do. A 2009 New England Journal of Medicine study led by Scott Plotkin, MD, PhD, at Massachusetts General Hospital reported that treatment with the antiangiogenesis drug bevacizumab caused shrinkage of NF2-schwannomas in most of the treated patients and improved hearing in more than half. But the limitations of that approach – the fact that not all patients responded, that the hearing improvement was often transient and that some patients could not tolerate long-term bevacizumab treatment – indicated the need to better understand the mechanisms of anti-angiogenesis on the function of tumor-bearing nerves.












