Clinical Relevance of Targeted Therapy and Immune-Checkpoint Inhibition in Lung Cancer

Abstract

Lung cancer (LC) represents the second most diagnosed tumor and the malignancy with the highest mortality rate. In recent years, tremendous progress has been made in the treatment of this tumor thanks to the discovery, testing, and clinical approval of novel therapeutic approaches. Firstly, targeted therapies aimed at inhibiting specific mutated tyrosine kinases or downstream factors were approved in clinical practice. Secondly, immunotherapy inducing the reactivation of the immune system to efficiently eliminate LC cells has been approved. This review describes in depth both current and ongoing clinical studies, which allowed the approval of targeted therapies and immune-checkpoint inhibitors as standard of care for LC. Moreover, the present advantages and pitfalls of new therapeutic approaches will be discussed. Finally, the acquired importance of human microbiota as a novel source of LC biomarkers, as well as therapeutic targets to improve the efficacy of available therapies, was analyzed. Therapy against LC is increasingly becoming holistic, taking into consideration not only the genetic landscape of the tumor, but also the immune background and other individual variables, such as patient-specific gut microbial composition. On these bases, in the future, the research milestones reached will allow clinicians to treat LC patients with tailored approaches.

TRPM2-mediated Ca2+ signaling as a potential therapeutic target in cancer treatment: an updated review of its role in survival and proliferation of cancer cells

“…It has been suggested that, in the case of cardiomyocytes, stimulation of the TRPM2 channel, as well as poly(ADP-ribose) polymerase, is expected to be engaged in oxidative stress-prompted cell death [ 54 ]. In cancer, the production of ROS by mitochondria promotes cellular oncogenesis by shaping signaling pathways and specific transcription factors [ 55 ]. TRPM2 maintains the bioenergy of cancer cells by maintaining mitochondrial activity and increased ROS production [ 38 , 56 ].…”

Anticancer activity and other biomedical properties of β‐sitosterol: Bridging phytochemistry and current pharmacological evidence for future translational approaches

“…The most important anticancer mechanisms are summarized in Lung cancer, predominantly caused by prolonged tobacco smoking, remains the leading cause of cancer-related mortality worldwide. Its complex heterogeneity, with non-small-cell lung cancer being the most common subtype, underscores the imperative need for early detection and individualized therapeutic strategies (Leone et al, 2023). EMT is linked with metastasis, invasiveness, tumorigenesis, and therapeutic resistance (Pastushenko & Blanpain, 2019).…”

“…During metastasis, EMT conferred migratory as well as invasive capacity to cancerous cells. Following the induction of EMT, cancer cells depicted bolstered aggressive stem-like features and become rebellious to apoptosis (Leone et al, 2023;Suarez-Carmona et al, 2017). β-sitosterol has inhibited transforming growth factor-β1 (TGF-β1)-induced EMT in human alveolar epithelial cells and consequently attenuated the pulmonary fibrosis.…”

The incidence and mortality of lung cancer in China: a trend analysis and comparison with G20 based on the Global Burden of Disease Study 2019

“…However, it demonstrated an increase trend in incidence in female in China ( 8 ). Although new treatment strategies, such as targeted therapies that inhibit specific mutated tyrosine kinases or downstream factors ( 9 ), immunotherapy that reactivates the immune system to eliminate LC cells ( 10 ), novel multi-tier biotechnology treatments ( 1 , 11 ), and etc ( 12 , 13 ), have emerged, the success rate of therapy remains relatively low. Moreover, the prognosis for late-stage lung cancer patients is worse than for other types of cancer.…”