MEK inhibitors for the treatment of non-small cell lung cancer

Abstract

BRAF and KRAS are two key oncogenes in the RAS/RAF/MEK/MAPK signaling pathway. Concomitant mutations in both KRAS and BRAF genes have been identified in non-small cell lung cancer (NSCLC). They lead to the proliferation, differentiation, and apoptosis of tumor cells by activating the RAS/RAF/MEK/ERK signaling pathway. To date, agents that target RAS/RAF/MEK/ERK signaling pathway have been investigated in NSCLC patients harboring BRAF mutations. BRAF and MEK inhibitors have gained approval for the treatment of patients with NSCLC. According to the reported findings, the combination of MEK inhibitors with chemotherapy, immune checkpoint inhibitors, epidermal growth factor receptor-tyrosine kinase inhibitors or BRAF inhibitors is highly significant for improving clinical efficacy and causing delay in the occurrence of drug resistance. This review summarized the existing experimental results and presented ongoing clinical studies as well. However, further researches need to be conducted to indicate how we can combine other drugs with MEK inhibitors to significantly increase therapeutic effects on patients with lung cancer.

A Review on Cancer Immunotherapy and Applications of Nanotechnology to Chemoimmunotherapy of Different Cancers

“…In addition, clinical trials are ongoing on new immune checkpoint inhibitors. For example, success in the treatment of solid tumors is observed in phase I studies with antibodies targeted to CD47, CD73, A2Ar and TIM-3 [ 41 ].…”

Administration of COVID-19 vaccines in immunocompromised patients

“…As viral vector vaccines enter the cells, they use the cells’ protein-making machinery to produce their antigens, which are S proteins displayed on the cells' surface. When these antigens are expressed on the cell surface, they trigger an immune response in the patient including both cellular and humoral responses [39] , [41] .…”

“…A similar response was observed in patients who received the inactivated influenza vaccine. Overall, it seems that vaccination can generate a proper immune response except for periods of intensive chemotherapy [41] .…”

“…Controversially, 7-26% of patients on ibrutinib had impaired response and experienced seroconversion following an influenza vaccine, while about 75% of patients could respond to the varicella-zoster virus (VZV) subunit vaccine [78] , [79] . However, it seems that patients with cancer thatare receivingtargeted therapies can still produce enough immune response against vaccines [41] .…”

“…Moreover, it seems that radiotherapy could not completely impair the immune system and consequent ineffectiveness of vaccine immunization. As a result, vaccination in patients onradiotherapy could be safe [41] .…”