AMLo collaborates on ground-breaking paper
Professor Penny Lovat (CSO) and Dr Marie Labus (CEO) of AMLo Biosciences Ltd. are proud to have collaborated with the team at the National Institute of Infectious Diseases in Rome to publish a ground-breaking paper on the role of AMBRA1 in OPSCC (oropharyngeal squamous cell carcinoma).
OPSCC is a head and neck cancer that particularly affects younger people, causing approximately 97,000 deaths worldwide. Incidence is increasing, particularly in Western countries and is linked to human papilloma virus (HPV) type-16 infection, which promotes tumour genesis. Recent studies suggest that 70% of OPSCC are HPV-positive. Negative outcomes from therapy de-escalation studies amongst HPV-positive patients suggested that there is also heterogeneity within HPV-positive tumours as a group. This reduces the validity of the assumption that HPV-positivity presents a lower risk. Thus, although they tend to have a better prognosis than their HPV-negative counterparts, it is important to stratify individual risk for HPV-positive patients, to personalise therapy and modify treatment to avoid serious morbidity associated with toxicity of therapeutic regimens.
AMBRA1 expression appears to be reduced in HPV-positive OPSCC disease. This paper demonstrates the mechanism by which AMBRA1 is degraded by HPV, leading to reduced autophagy in HPV-positive cells. Cancer cells use autophagy to promote tumour growth, so reduced autophagy may be linked to improved survival rates.
Additionally, it also shows that induced AMBRA1 downregulation and consequential inhibition of autophagy in HPV-negative OPSCC leads to a greater sensitivity of these tumours to the cytotoxic effects of cisplatin. Patients with HPV-negative OPSCC have a poorer prognosis. The role of AMBRA1 in regulating autophagy in HPV-negative OPSCC, demonstrated here, suggests autophagy modulation as a potential therapeutic strategy.
Together, the data reveals AMBRA1 as a putative prognostic indicator in OPSCC, which may also represent a novel means through which to aid stratification of patients with HPV +ve OPSCC for therapy de-escalation.
The full paper may be accessed via Taylor & Francis Online.