A University of Sheffield researcher has uncovered new evidence that could help improve treatment options for patients with hard-to-treat throat cancer.
Throat cancer, specifically oropharyngeal cancer, is becoming increasingly common in the UK and worldwide. It exists in two forms: one caused by Human Papilloma Virus (HPV-associated) and another that develops independently of the virus (HPV-independent). Both forms are commonly treated with the chemotherapy drug cisplatin, but many tumours eventually become resistant to the drug, making them far more difficult to treat.
Dr Hannah Crane, NIHR Clinical Lecturer in Oral and Maxillofacial Pathology, set out to understand why this resistance develops, and whether a little-known molecular structure inside cells called an R-loop plays a role. R-loops form when RNA, the molecule responsible for carrying genetic instructions, reattaches itself to DNA. These structures can have both helpful and harmful effects within cells, but their involvement in cisplatin resistance had not previously been explored.
Using cancer cells grown in the laboratory, Dr Crane and colleagues developed models of cisplatin-resistant oropharyngeal cancer. This allowed the team to closely examine how R-loops behave in resistant cells and whether they could influence how the cancer responds to treatment.
The study’s key discovery was that in HPV-associated cancer cells, increasing the levels of R-loops could partially reverse cisplatin resistance. This early finding suggests that manipulating R-loops may one day help make resistant tumours more responsive to treatment.
The research could have important implications for future patient care. Hannah from the University of Sheffield’s School of Clinical Dentistry, said: “Survival rates for head and neck cancer have remained relatively unchanged for decades. Understanding why some tumours stop responding to chemotherapy is vital, because it opens the door to developing new treatment strategies.”
While further research is needed before the findings can be translated into clinical practice, the work provides a promising new direction for improving outcomes in patients with head and neck cancer.
Dr Crane acknowledged the support that made the project possible: “I am grateful to everyone who has contributed to this research over the years, including Wellcome 4ward North, who funded my Clinical PhD fellowship, as well as my colleagues and the patient contributors who shared their experiences.”
The full research article is available in iScience.