Impact of DNA Damage Response-Targeted Therapies on the Immune Response to Tumours.

The DNA damage response (DDR) maintains the stability of a genome faced with genotoxic insults (exogenous or endogenous), and aberrations of the DDR are a hallmark of cancer cells. These cancer-specific DDR defects present new therapeutic opportunities, and different compounds that inhibit key components of DDR have been approved for clinical use or are in various stages of clinical trials. Although the therapeutic rationale of these DDR-targeted agents initially focused on their action against tumour cells themselves, these agents might also impact the crosstalk between tumour cells and the immune system, which can facilitate or impede tumour progression. In this review, we summarise recent data on how DDR-targeted agents can affect the interactions between tumour cells and the components of the immune system, both by acting directly on the immune cells themselves and by altering the expression of different molecules and pathways in tumour cells that are critical for their relationship with the immune system. Obtaining an in-depth understanding of the mechanisms behind how DDR-targeted therapies affect the immune system, and their crosstalk with tumour cells, may provide invaluable clues for the rational development of new therapeutic strategies in cancer.

MET Inhibitors in Small Cell Lung Cancer: From the Bench to the Bedside.

Small cell lung cancer (SCLC) is the most aggressive type of lung cancer. The different systemic treatment approaches attempted in the last 35 years have not improved overall survival in the advanced stage. Targeted therapies assessed in clinical trials have failed to show efficacy against SCLC. Within the potentially interesting targets, the hepatocyte growth factor (HGF)/mesenchymal-epithelial transition (MET) pathway activation is associated with worse survival and chemoresistance in SCLC. Preclinical data suggest that the inhibition of the MET pathway can revert chemoresistance and prevent tumor growth. Recently, immunotherapy has shown modest but relevant activity in SCLC. Interestingly, MET modulation seems to be involved in increasing the efficacy of standard checkpoint inhibitors. Here, we review the preclinical and clinical data of MET inhibition in SCLC, and the role of this pathway in the immune response.