Recent research published in Nature Cancer has revealed that a gene called CDKN2A, previously believed to drive the development of oesophageal cancer, may actually have a protective role early in the disease. This unexpected discovery could help doctors identify individuals at greater risk of developing cancer and lead to more personalized and effective preventive strategies. The study was led by Francesca Ciccarelli, Professor of Cancer Genomics at Queen Mary University of London’s Barts Cancer Institute and funded by Cancer Research UK.
Oesophageal cancer has a low 10-year survival rate, with the UK having one of the highest incidences of a subtype called oesophageal adenocarcinoma. This cancer type often develops from a condition called Barrett’s oesophagus, where the cells lining the oesophagus become abnormal. However, only a small percentage of individuals with Barrett’s go on to develop cancer each year. The research team analyzed gene sequencing data from over 1,000 patients with oesophageal adenocarcinoma and found that defects in the CDKN2A gene were more common in individuals with Barrett’s oesophagus who never progressed to cancer, challenging the conventional view of this gene as a tumour suppressor.
The study revealed that the loss of CDKN2A in normal oesophageal cells promotes the development of Barrett’s oesophagus but also protects cells against the loss of another critical gene encoding p53, a key tumour suppressor. Cells that lose both CDKN2A and p53 are weakened and unable to compete with surrounding cells, preventing the development of cancer. However, if cancer cells lose CDKN2A later in the disease progression, it promotes a more aggressive form of cancer and poorer outcomes for patients.
The dual role of CDKN2A has been likened to the ancient Roman god Janus, with two faces looking in opposite directions. The findings challenge the simplistic perception of cancer mutations as purely good or bad and demonstrate that mutations can have multiple effects, including a protective role in some cases. The research suggests that CDKN2A mutations could be used to assess cancer risk in individuals with Barrett’s oesophagus, indicating whether the disease is less likely to progress to cancer based on the timing of the mutation.
The implications of this study for assessing cancer risk and prognosis are significant, as it provides new insights into the complex role of mutations in cancer development. Further research is needed to determine how to best apply this knowledge in clinical settings to benefit patients. The findings underscore the importance of funding research to advance our understanding of cancer and improve outcomes for individuals affected by the disease.
In conclusion, the study sheds light on the dual nature of cancer mutations and their impact on disease progression in oesophageal cancer. By challenging conventional beliefs about the role of the CDKN2A gene in cancer development, the research opens up new possibilities for personalized cancer prevention and treatment strategies. Continued research in this area is critical to unraveling the complexities of cancer and identifying innovative approaches to combat the disease.