TY - JOUR
T1 - NRF2, p53, and p16
T2 - Predictive biomarkers to stratify human papillomavirus associated head and neck cancer patients for de-escalation of cancer therapy
AU - Ramesh, Pushkal S.
AU - Devegowda, Devananda
AU - Singh, Anju
AU - Thimmulappa, Rajesh K.
N1 - Funding Information:
Rajesh K Thimmulappa (RKT) acknowledges the funding from D epartment of Biotechnology, Ramalingaswami Re-entry Fellowship, Government of India. Pushkal S Ramesh (PSR) acknowledges the award of Junior Research Fellowship from Council of Scientific and Industrial Research (CSIR), Government of India.
Funding Information:
Rajesh K Thimmulappa (RKT) acknowledges the funding from Department of Biotechnology, Ramalingaswami Re-entry Fellowship, Government of India. Pushkal S Ramesh (PSR) acknowledges the award of Junior Research Fellowship from Council of Scientific and Industrial Research (CSIR), Government of India.
Funding Information:
Pushkal S Ramesh is a doctoral student at the Center for Excellence in Molecular Biology & Regenerative Medicine, Department of Biochemistry, JSS Medical College, Mysuru. He is currently pursuing research on understanding the mechanism underlying better therapeutic responses of HPV associated Head & Neck Cancers. He has been awarded Junior Research Fellowship from Council of Scientific and Research (CSIR), Government of India. He is also a recipient of Young Scientist award and International Travel support from Department of Biotechnology, Science & Engineering Research Board (DST-SERB), Government of India for attending 32nd International Papillomavirus Conference (IPVC), held on October 2–6, 2018 in Sydney, Australia.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/4
Y1 - 2020/4
N2 - Patients with HPV associated (HPV+ve) head and neck squamous cell carcinoma (HNSCC), particularly oropharyngeal cancer, show better treatment response, higher survival rates, and lower risks of recurrence as compared to HPV−ve HNSCC patients. Despite increased sensitivity to treatment modality, HPV+ve HNSCC patients are subjected to the same intensive anti-cancer therapy as HPV−ve HNSCC patients and thus subjecting them to unwarranted long-term toxicity. To identify predictive biomarkers for risk-stratification, we have analyzed the mutational spectrum, and the evidence suggests that gain-of-function mutations in the NRF2 pathway are highly prevalent in HPV−ve HNSCC. At the same time, it is rare in HPV+ve HNSCC tumors. We have reviewed the importance of gain-of-NRF2 function and loss of p53 in the prognosis of HNSCC patients and discussed a predictive scoring system using a combination of HPV status (p16), NRF2 pathway and p53 to stratify HPV+ve HNSCC into good versus poor responders, which could immensely help in guiding future de-escalation treatment approaches in patients with HPV+ve HNSCC.
AB - Patients with HPV associated (HPV+ve) head and neck squamous cell carcinoma (HNSCC), particularly oropharyngeal cancer, show better treatment response, higher survival rates, and lower risks of recurrence as compared to HPV−ve HNSCC patients. Despite increased sensitivity to treatment modality, HPV+ve HNSCC patients are subjected to the same intensive anti-cancer therapy as HPV−ve HNSCC patients and thus subjecting them to unwarranted long-term toxicity. To identify predictive biomarkers for risk-stratification, we have analyzed the mutational spectrum, and the evidence suggests that gain-of-function mutations in the NRF2 pathway are highly prevalent in HPV−ve HNSCC. At the same time, it is rare in HPV+ve HNSCC tumors. We have reviewed the importance of gain-of-NRF2 function and loss of p53 in the prognosis of HNSCC patients and discussed a predictive scoring system using a combination of HPV status (p16), NRF2 pathway and p53 to stratify HPV+ve HNSCC into good versus poor responders, which could immensely help in guiding future de-escalation treatment approaches in patients with HPV+ve HNSCC.
KW - Chemoradioresistance
KW - HPV
KW - NRF2
KW - Oropharyngeal cancer
KW - Therapeutic de-escalation
KW - p53
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U2 - 10.1016/j.critrevonc.2020.102885
DO - 10.1016/j.critrevonc.2020.102885
M3 - Review article
C2 - 32062315
AN - SCOPUS:85079139433
SN - 1040-8428
VL - 148
JO - Critical Reviews in Oncology/Hematology
JF - Critical Reviews in Oncology/Hematology
M1 - 102885
ER -