research directions for lung cancer treatment

Research directions[edit]

Current research directions for lung cancer treatment include immunotherapy,^[164] which encourages the body's immune system to attack the tumour cells, epigenetics, and new combinations of chemotherapy and radiotherapy, both on their own and together. Many of these new treatments work through immune checkpoint blockade, disrupting cancer's ability to evade the immune system.^[164]

Ipilimumab blocks signaling through a receptor on T cells known as CTLA-4 which dampens down the immune system. It has been approved by the U.S. Food and Drug Administration (FDA) for treatment of melanoma and is undergoing clinical trials for both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).^[164]

Other immunotherapy treatments interfere with the binding of programmed cell death 1 (PD-1) protein with its ligand PD-1 ligand 1 (PD-L1). Signaling through PD-1 inactivates T cells. Some cancer cells appear to exploit this by expressing PD-L1 in order to switch off T cells that might recognise them as a threat. Monoclonal antibodies targeting both PD-1 and PD-L1, such as pembrolizumab and nivolumab^[165]are currently in clinical trials for treatment for lung cancer.^[164]

Epigenetics is the study of small, usually heritable, molecular modifications – or ‘tags’- that bind DNA and modify gene expression levels. Targeting these ‘tags’ with drugs can kill cancer cells. Early-stage research in NSCLC using drugs aimed at epigenetic modifications shows that blocking more than one of these ‘tags’ can kill cancer cells with fewer side effects.^[166] Studies also show that giving patients these drugs before standard treatment can improve its effectiveness. Clinical trials are underway to evaluate how well these drugs kill lung cancer cells in humans.^[166] Several drugs that target epigenetic mechanisms are in development. Histone deacetylase inhibitors in development include valproic acid, vorinostat, belinostat, panobinostat, entinostat, and romidepsin. DNA methyltransferase inhibitors in development include decitabine, azacytidine, and hydralazine.^[52]

The TRACERx project is looking at how NSCLC develops and evolves, and how these tumours become resistant to treatment.^[167] The project will look at tumour samples from 850 NSCLC patients at various stages including diagnosis, after first treatment, post-treatment, and relapse.^[168] By studying samples at different points of tumour development, the researchers hope to identify the changes that drive tumour growth and resistance to treatment. The results of this project will help scientists and doctors gain a better understanding of NSCLC and potentially lead to the development of new treatments against the disease.^[167]

For lung cancer cases that develop resistance to epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors, new drugs are in development. New EGFR inhibitors include afatinib and dacomitinib. An alternative signaling pathway, c-Met, can be inhibited by tivantinib and onartuzumab. New ALK inhibitors include crizotinib and ceritinib.^[169]