Lung cancer is the fifth most common cancer and the highest cause of cancer-related death. Incidence in women has increased in recent years. The risk of being diagnosed with lung cancer in Australia by age 85 is 1 in 13 for men and 1 in 21 for women. The five-year survival rate is only 17%. Lung cancer claims more lives every year than cancers of the breast, prostate, and colon combined.
The most common cause of lung cancer is long-term exposure to tobacco smoke, which causes 80-90% of lung cancers. Non-smokers account for 10-15% of lung cancer cases, and these cases are often attributed to a combination of genetic factors, asbestos and air pollution including second-hand smoke. Although aided by anti-tobacco measures, survival remains low, and a significant stigma is attached to the disease.
Lung cancer is subdivided into two major types: small cell lung cancer (SCLC) comprises approximately 10-15% of all known lung cancer cases; and non-small cell lung cancer (NSCLC) comprises approximately 85-90% of all known lung cancer cases. Although targeted therapies offer treatment options for the small subset of patients, these therapies are ineffective in those whose tumours lack such genetic alterations, who comprise the majority of NSCLC patients. In these patients, immunotherapy alone, or in combination with conventional treatments such as chemotherapy, can significantly improve overall survival.
There are two key causes for the high mortality associated with lung cancer: late diagnosis and suboptimal therapies. When most lung cancer patients become symptomatic and are diagnosed, the disease has already advanced to late stage (approximately 75% at stage IIIb/IV). At these stages, surgery, chemotherapy, and radiation rarely offer cure. Early detection methods are urgently needed, as are new treatments for patients facing a lung cancer diagnosis.
One of the biggest obstacles to clinical benefit of traditional chemo/radiation and immune checkpoint inhibitor (ICI) is that the treatments are often not directed as precisely as possible to those patients who are most likely to benefit. Currently, multiple biomarkers are being investigated to explore their predictive value of response to ICI. This includes analysis of the molecular information accrued from combined tumour immunohistochemistry/genetics/epigenetics/ proteomics and exosome analyses.
Responses to immunotherapy have the potential for remarkable durability, but occur in only a minority of patients. The approved immunotherapy strategies are mostly effective in a “hot” (T cell-rich and inflamed) tumour microenvironment (TME) and ineffective in a “cold” (non-inflamed and T cell-poor) TME. However, there is still an unmet medical need to develop new combination immunotherapies that suppress tumour growth and spread in a broader range of cancer patients not catered for by currently approved immunotherapy. These patients often fail therapy because their cancers are “cold” or have developed immune escape mechanisms in the TME. This experience highlights two primary opportunities for improving immunotherapy success: 1) identification of predictive biomarkers of response; and 2) development of combination treatment approaches that improve the frequency, depth, and duration of response, particularly in those with a “cold” tumour.
*LUCKISTARS members within these labs
The LUCKI STARS (Lung cancer knowledge in immunogenomics to stratify therapeutic resistance and sensitivity) is a nationally well-connected 11-member multi-disciplinary research team at both QIMR Berghofer and Metro North combining the expertise of outstanding clinical and basic scientists to improve the life of lung cancer patients. This team with ACCR-Cancer Council Queensland and other leveraged support are exploring the immunogenomics and immunoproteomics landscape of lung cancer.