Lung cancer is the leading cause of cancer-related mortality worldwide, primarily driven by genetic mutations. The most common genetic alterations implicated in lung cancer include mutations in TP53, KRAS, KEAP1, NF1, EGFR, NRF2, ATM, ALK, Rb1, BRAF, MET, and ERBB2. Targeted therapies have been developed to inhibit cancer growth by focusing on these specific genetic mutations. However, either the mutations are undruggable or the efficacy of these therapies is often compromised over time due to the emergence of drug resistance, which can occur through additional mutations in the targeted protein or alternative growth signaling pathways. In recent years, immunotherapy has emerged as a promising approach to enhance the effectiveness of cancer treatment by leveraging the body’s immune system. Notable advancements include immune checkpoint inhibitors, monoclonal antibodies targeting cell surface receptors, antibody–drug conjugates, and bispecific antibodies. This review provides an overview of the mechanisms of FDA-approved immunotherapeutic drugs, offering an updated perspective on the current state and future developments in lung cancer therapy. More importantly, the factors that positively and negatively impact the immunotherapy’s efficacy will also be discussed.

Research on Rab-like protein 1A (RBEL1A) in the past two decades highlighted the oncogenic properties of this gene. Despite the emerging evidence, its importance in cancer biology was underrated. This is the first RBEL1A critical review covering its discovery, biochemistry, physiological functions, and clinical insights. RBEL1A expression at the appropriate levels appears essential in normal cells and tissues to maintain chromosomal stability; however, its overexpression is linked to tumorigenesis. Furthermore, the upstream and downstream targets of the RBEL1A signaling pathways will be discussed. Mechanistically, RBEL1A promotes cell proliferation signals by enhancing the Erk1/2, Akt, c-Myc, and CDK pathways while blunting the apoptotic signals via inhibitions on p53, Rb, and caspase pathways. More importantly, this review covers the clinical relevance of RBEL1A in the cancer field, such as drug resistance and poor overall survival rate. Also, this review points out the bottle-necks of the RBEL1A research and its future research directions. It is becoming clear that RBEL1A could potentially serve as a valuable target of anticancer therapy. Genetic and pharmacological researches are expected to facilitate the identification and development of RBEL1A inhibitors as cancer therapeutics in the future, which could undoubtedly improve the management of human malignancy.