17 November 2020
Identifying the possible mechanism of inferior response of HPV positive head and neck cancers to cetuximab
Recent studies carried out by PhD student Elham Alsahafi have identified a novel radiosensitising role for EGFR in HPV-positive HNC.
Head and neck cancers (HNC) are a prevalent malignancy with significant unmet medical needs. Although the prevalence of smoking associated HNC has decreased, the number of patients diagnosed with HNC caused by Human Papillomavirus (HPV) has increased dramatically over the last three decades.
HPV-HNC patients have a significantly better response to the standard of care therapy, but they are still treated similarly with high dose radio-chemotherapy suffering severe adverse side effects, so far subtype specific treatment strategies are unavailable. The only approved targeted therapy for HNSCC is the EGFR antibody Cetuximab. This has been used in several clinical trials for treatment de-intensification purposes, but these trials concluded a highly disadvantageous outcome for HPV-positive patients.
Recent studies supported by the Rosetrees Trust and sponsored by Umm Al-Qura University-Faculty of Dentistry, Saudi Arabia and carried out by PhD student Elham Alsahafi from Tavassoli Lab in the Centre for Host Microbiome Interactions at King’s College London have identified a novel radiosensitising role for EGFR in HPV-positive HNC. This is opposite to the EGFR role as a known radioresistance pathway in HPV-negative HNC. Collaborating with Ben Guerin University, Israel, these findings have been published in one of the main cancer journals, Cancer Letters. They provide, for the first time, a possible mechanism for the catastrophic outcome of HPV-positive HNC patients treated in combination with Cetuximab.
The academics believe these findings will have very important implications in the design of future clinical trials with ani-EGFR as well as other targeted therapies, suggesting the future use of these drugs needs to be considered in the context of the molecular makeup of the cancer.
The paper EGFR overexpression increases radiotherapy response in HPV-positive head and neck cancer through inhibition of DNA damage repair and HPV E6 downregulation was published 31 October 2020, and can be found online here: https://pubmed.ncbi.nlm.nih.gov/33137407/
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Professor of Molecular Oncology