Non-Small-Cell Lung Cancer: New Rare Targets—New Targeted Therapies—State of The Art and Future Directions

• Main Authors: Katarzyna Stencel, Izabela Chmielewska, Janusz Milanowski, Rodryg Ramlau
• Format: Article
• Language: English
• Published: MDPI AG 2021-04-01
• Series: Cancers
• Subjects: lung cancer; gene alterations; targeted therapy; <i>MET</i> amplification; <i>MET</i> skipping mutation; <i>NTRK</i> fusions
• Online Access: https://www.mdpi.com/2072-6694/13/8/1829

Lung cancer is the most common cause of cancer-related death worldwide, and the prognosis for stage IV remains poor. The presence of genetic alterations in tumor cells, such as <i>EGFR</i> and <i>BRAF</i> gene mutations, as well as <i>ALK</i> and <i>ROS1</i> gene rearrangements, are indications for targeted therapies. Many such treatments are already registered and used on a wide scale. In comparison to standard chemotherapy, they can prolong not only progression-free survival but also overall survival. Moreover, they are able to provide excellent quality of life and rapid improvement of cancer-related symptoms such as dyspnea, cough and pain. Recent years have witnessed great advances in both molecular diagnostics and new molecular therapies for non-small-cell lung cancer. This review presents new therapeutic targets in NSCLC, as well as drugs of which the activity against <i>NTRK</i>, <i>RET</i>, <i>MET</i> or <i>HER2</i> gene alterations (including <i>EGFR</i> exon 20 insertions) has either been confirmed or is currently being evaluated. Although these particular genetic alterations in NSCLC are generally rare, each accounting for 1–2% of patients, in total about half of all patients have molecular alterations and may ultimately receive targeted therapies.