Targeting Tumor Microenvironment for Lung Cancer Treatment

Chemotherapy as the widely used regimen of lung cancer treatment is designed to kill dividing cancer cells. In most cases, it does not affect non-cancer stromal cells that in turn are required to sustain tumor growth. The development of novel approaches for cancer therapy based on targeting tumor microenvironment including tumour vasculature, cancer-associated fibroblasts and immune cells is gaining significant interest as a direction to improve cancer treatment.

To understand further the role of tumor microenvironment in the development of a Non-Small-Cell-Lung-Cancer and thus to assess novel potential strategies for treatment, we used a mouse model of NSCLC with somatic expression of mutated K-ras. We monitored K-ras-induced lung tumor development in multiple mouse strains with inactivated or conditional deleted p38α MAPK which has been suggested to be involved in lung tumorigenesis.

We found that activity of p38α MAPK in lung stromal fibroblasts and in hematopoietic cells, mainly in macrophages, is essential to control lung tumor development in mouse model of NSCLC. We suggest that targeting of tumor-associated macrophages and lung stromal fibroblasts could be used as an efficient complementary therapy for the treatment of NSCLC with mutated K-ras.