ABSTRACT
BACKGROUND: Lung cancer is one of the highly lethal forms of cancer whose incidence has worldwide rapidly increased over the past few decades. About 80-85% of all lung cancer cases constitute non-small cell lung cancer (NSCLC), with adenocarcinoma, squamous cell carcinoma and large cell carcinoma as the main subtypes. Immune checkpoint inhibitors have led to significant advances in the treatment of a variety of solid tumors, significantly improving cancer patient survival rates. METHODS AND RESULTS: The cytotoxic drugs in combination with anti-PD-(L)1 antibodies is a new method that aims to reduce the activation of immunosuppressive and cancer cell prosurvival responses while also improving direct cancer cell death. The most commonly utilized immune checkpoint inhibitors for patients with non-small cell lung cancer are monoclonal antibodies (Atezolizumab, Cemiplimab, Ipilimumab, Pembrolizumab etc.) against PD-1, PD-L1, and CTLA-4. Among them, Atezolizumab (TECENTRIQ) and Cemiplimab (Libtayo) are engineered monoclonal anti programmed death ligand 1 (PD-L1) antibodies that inhibit binding of PD-L1 to PD-1 and B7.1. As a result, T-cell proliferation and cytokine synthesis are inhibited leading to restoring the immune homeostasis to fight cancer cells. CONCLUSIONS: In this review article, the path leading to the introduction of immunotherapeutic options in lung cancer treatment is described, with analyzing the benefits and shortages of the current immunotherapeutic drugs. In addition, possibilities to co-administer immunotherapeutic agents with standard cancer treatment modalities are also considered.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Lung Neoplasms/pathology , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , B7-H1 Antigen , Immune Checkpoint Inhibitors/therapeutic use , Programmed Cell Death 1 Receptor , Immunotherapy/methodsABSTRACT
Celastrol is a highly investigated anticancer moiety. It is a pentacyclic triterpenoid, isolated several decades ago with promising role in chemoprevention. Celastrol has been found to target multiple proinflammatory, angiogenic and metastatic proteins. Inhibition of these targets results in significant reduction of cancer growth, survival and metastasis. This review summarizes the varied molecular targets of celastrol along with insight into the various recently published clinical, preclinical and industrial patents (2011-2017).
