Washington: Researchers have now discovered that a combination of immune checkpoint blockade and targeted therapies that block normal DNA damage repair (DDR) achieved significant tumour regression in mouse models of small cell lung cancer (SCLC).
The University of Texas MD Anderson Cancer Center research suggests a promising new approach for treating patients with this aggressive cancer. The research, published in Cancer Discovery, suggest that the PARP inhibitor olaparib and other DDR inhibitors induce a rapid immune response and sensitise SCLC cells to immunotherapy, to which they were previously resistant.
According to corresponding author of the study Lauren Averett Byers, small cell lung cancer, one of the most aggressive types of cancer, makes up about 15 per cent of all lung cancers diagnosed in the US alone.
Standard treatment for advanced SCLC is chemotherapy, but recurrence is common and the average survival is only about 12 months, according to Byers. For about 30 years, there were no changes to this approach, but recently the use of immunotherapy in combination with chemotherapy has become a new standard. However, the benefits are minimal for patients.
Speaking about it, Byers said, “While the use of immunotherapy has revolutionised the way we treat lung cancer, we find that small cell lung cancers can escape the immune system very effectively, so we see a much lower response rate.” He further added, "However, we want to do a lot better for our patients, and we think there's a lot of room for further improvement."
Byers added, "We found that if we added either PARP or CHK1 inhibitors to immunotherapy, we saw a dramatic shrinkage of tumours. In fact, in some cases, the tumours disappeared completely." He further shared, "I think the results from this study are really compelling because of the dramatic activity that we saw with the combination of adding a targeted therapy to immune therapy. I think our findings can be rapidly translated into the clinic for our patients and also to other cancer types."
Byers and colleagues hope to launch clinical trials to investigate the combination approach later this year, and expect this may also be effective in other cancer types defined by increased DNA damage, such as BRCA-mutant breast and ovarian cancers.
This study was supported by the Lung Cancer Moon Shot™, part of MD Anderson's Moon Shots Program™, a collaborative effort to accelerate the development of scientific discoveries into clinical advances that save patients' lives.