Beyond Chemotherapy and Immunotherapy in Thoracic Malignancies: Overcoming Resistance by Tackling New Molecular Pathways

Chemotherapy and Immunotherapy, either given sequentially or concurrently, represent the current standard of care for the vast majority of patients with advanced non-small cell lung cancer and other thoracic malignancies. However, even when administered as a combination in first-line treatment, chemo-imunotherapy achieves a response rate of 50-60% and a median OS of less than two years according to clinical trial data.

Patients with advanced NSCLC who progress after chemo-immunotherapy, administered either concurrently or sequentially, have limited treatment options. Second-line chemotherapy with docetaxel, administered either alone or in combination with ramucirumab offers modest clinical outcomes. Recent advances in the elucidation of the molecular biology of the disease have led to the identification of molecular pathways of resistance that could be exploited therapeutically in an effort to improve outcomes by overcoming resistance to immunotherapy and chemotherapy

The scope of the current Research Topic is to present the new treatment strategies used to overcome resistance to chemo-immunotherapy by identification of the molecular mechanisms of resistance and exploiting therapeutically with new combinations of agents targeting distinct molecular pathways.

Examples:

· Combinations of immune checkpoint inhibitors (ie anti-PD-(L)1 and anti-CTLA4)

· Combinations of immune checkpoint inhibitors with tyrosine kinase inhibitors

· New monoclonal antibodies (ie anti-CEACAM5, anti-TIGIT, Anti-LAG3)

· Bispecific antibodies, novel pathways

· New molecular agents for SCLC, mesothelioma, thymic carcinoma