These findings come from a study by William Lockwood, PhD, and colleagues from the BC Cancer Agency, an agency of the Provincial Health Services Authority, published in this week’s PLoS Medicine.
Lockwood, the study’s primary investigator, sees these results forging a path toward more precise and personalized treatment of lung cancer subtypes. He says, “These findings demonstrate that lung cancer subtypes activate different genes for tumour initiation and progression, suggesting that the conventional ‘one size fits all’ approach for therapeutic intervention may not succeed.” Lockwood adds, “Our data highlights the need to tailor therapies to the specific cancer subtypes.”
Traditionally, non-small cell lung carcinoma (NSCLC), which accounts for 70 per cent of lung cancer cases, has been treated as a single disease. Emerging evidence suggests that the two major subtypes of NSCLC—adenocarcinoma and squamous cell carcinoma respond differently to chemotherapy. By identifying the underlying characteristics, such as the BRF2 gene, of lung cancer sub-types, clear targets can be defined for the development of more effective therapies and disease management.
Lung cancer is the most common cause of cancer death for both men and women in North America, accountable for approximately 27 per cent of all cancer deaths. Scientists analyzed the changes in the DNA of lung cancer samples and found that focal regions of Chromosome 8p12 are amplified in about 40 per cent of squamous lung cell carcinoma, whereas loss of DNA in this region is the most common mutation in lung adenocarcinoma. The cancer-causing gene disrupted by this alteration, BRF2, was also found to be frequently activated in pre-invasive stages of lung squamous cell carcinoma — carcinoma in situ and dysplasia—which are curable if diagnosed before advancing to full tumours.
When scientists artificially induced expression of BRF2 in lung cells the normal cells began to behave like tumour cells, and, when BRF2 expression was reduced, the cells began to behave like normal lung cells.
The authors conclude: “This is the first study to show that the disruption of Chromosome 8p12 is unique to a specific lung cancer subtype and suggests that genetic activation of BRF2 plays an important role in the genesis of squamous lung cell carcinoma.” They add, “It [BRF2] can serve as a marker for early diagnosis for this disease and may ultimately provide a novel target for therapy.”
The BC Cancer Agency, an agency of the Provincial Health Services Authority, is committed to reducing the incidence of cancer, reducing the mortality from cancer, and improving the quality of life of those living with cancer. It provides a comprehensive cancer control program for the people of British Columbia by working with community partners to deliver a range of oncology services, including prevention, early detection, diagnosis and treatment, research, education, supportive care, rehabilitation and palliative care. The BC Cancer Foundation raises funds to support research and enhancements to patient care at the BC Cancer Agency. www.bccancer.bc.ca
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