The Evolution of Therapies in Non-Small Cell Lung Cancer

Abstract

The landscape of advanced non-small lung cancer (NSCLC) therapies has rapidly been evolving beyond chemotherapy over the last few years. The discovery of oncogenic driver mutations has led to new ways in classifying NSCLC as well as offered novel therapeutic targets for anticancer therapy. Targets such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements have successfully been targeted with appropriate tyrosine kinase inhibitors (TKIs). Other driver mutations such as ROS, MET, RET, BRAF have also been investigated with targeted agents with some success in the early phase clinical setting. Novel strategies in the field of immune-oncology have also led to the development of inhibitors of cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death-1 receptor (PD-1), which are important pathways in allowing cancer cells to escape detection by the immune system. These inhibitors have been successfully tried in NSCLC and also now bring the exciting possibility of long term responses in advanced NSCLC. In this review recent data on novel targets and therapeutic strategies and their future prospects are discussed.

Identification of a small molecule inhibitor of 3-phosphoglycerate dehydrogenase to target serine biosynthesis in cancers

“…Notably, elevated PHGDH expression correlates with clinical aggressiveness and poor prognosis in TNBC (13,16) and NSCLC (15). There is a paucity of targeted therapies for these cancers and chemotherapies are frequently used (29,30). Thus, the clinical potential of PHGDH inhibitors as targeted agents for TNBC and NSCLC tumors addicted to serine synthesis, as a single agent or in combination with standard of care, is an exciting perspective.…”

A real‑world study of treatment patterns and survival outcome in advanced anaplastic lymphoma kinase‑positive non‑small‑cell lung cancer

“…In 2015, an estimated 733,300 new cases of lung and bronchial cancer were diagnosed, and 610,200 mortalities were estimated to occur in China as a result of this disease (2). Approximately 80% of lung cancer cases involve non-small-cell lung cancer (NSCLC), which has an overall 5-year relative survival rate of <20%, while an exceptionally high mortality rate is reported for patients with advanced NSCLC (3). During the past decades, genomic medicine has increased our understanding of the molecular characterization of cancer.…”

“…During the past decades, genomic medicine has increased our understanding of the molecular characterization of cancer. The treatment strategy for advanced NSCLC has changed from the traditional chemotherapy based on pathologic histology to individualized precision treatment based on the oncogenic drivers (3).…”

“…In 2011, this drug received accelerated approval under the US Food and Drug Administration (FDA) for treating ALK-positive advanced NSCLC patients based on two single-arm clinical trials, namely PROFILE 1001 and PROFILE 1005 (7,8). Subsequently, crizotinib was evaluated A real-world study of treatment patterns and survival outcome in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer YING JIN 1,2 , YAMEI CHEN 2 , XINMIN YU 1,3 and XUN SHI in several randomized clinical trials, demonstrating superior response rate (RR) and progression-free survival (PFS) to chemotherapy, in first-and second-line settings (PROFILE 1007 and PROFILE 1014) (9,10). Recently, another first-line randomized trial (PROFILE 1029) with the same design as PROFILE 1014, confirmed that crizotinib was able to improve the objective RR (ORR) and PFS compared with chemotherapy in the Asian populations (11).…”

Detection of circulating tumor cells in non-small cell lung cancer

“…The discovery of oncogenic driver mutations has led to new ways in classifying NSCLC as well as new therapeutic modalities (4). Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements were targeted successfully with appropriate tyrosine kinase inhibitors (TKIs).…”