Lung cancer in a genetically engineered mouse model driven by the Kras oncogene (purple). Image credit: National Cancer Institute, National Institutes of Health (CC BY-NC 2.0)
Lung cancer remains the leading cause of all cancer-related deaths. Treatment options are limited because drug-based therapies including chemotherapy and immune checkpoint inhibitors (or ICIs, for short) are ineffective in most patients.
PDLIM2 is a protein that normally prevents tumors from forming by regulating the activities of other genes. However, lung cancer cells generally have lower levels of this protein than healthy cells and this appears to be linked to the ability of the cancer cells to become resistant to chemotherapy and ICIs. Cells make proteins using templates encoded in our DNA. It remains unclear how PDLIM2 production is repressed in lung cancer: it is possible that cancer cells may acquire genetic alterations that affect PDLIM2 production, or there may be other changes to the structure of the DNA known as epigenetic changes.
Sun et al. investigated the production of PDLIM2 in samples from human lung cancer patients. The experiments found that in over 90% of the patients, the levels of PDLIM2 were lower than in cells from healthy individuals. This was due to genetic alterations or epigenetic changes, or a combination of the two.
Further experiments in a mouse model of lung cancer demonstrated that it is possible to use nanotechnology to deliver PDLIM2 to cancer cells for effective cancer therapy with low toxicity. Combining this nanotechnology (known as nanoPDLIM2) with both ICIs and chemotherapy drugs was able to completely eradicate all tumors in most of the mice.
The findings provide a firm basis for further studies of the potential of nanoPDLIM2 as a safe and effective therapy for human lung cancer. PDLIM2 production is also repressed in numerous other types of cancer, so it is possible that nanoPDLIM2 may have broader uses in cancer treatment.
