Non-small cell lung carcinoma (NSCLC) comprises 80%–85% of lung cancer cases. EGFR is involved in several cancer developments, including NSCLC. The EGFR pathway regulates the Bax/Bcl-2 cascade in NSCLC. Increasing understanding of the molecular mechanisms of fundamental tumor progression has guided the development of numerous antitumor drugs. The development and improvement of rationally planned inhibitors and agents targeting particular cellular and biological pathways in cancer have been signified as a most important paradigm shift in the strategy to treat and manage lung cancer. Newer approaches and novel chemotherapeutic agents are required to accompany present cancer therapies for improving efficiency. Using natural products as a drug with an effective delivery system may benefit therapeutics. Naturally originated compounds such as phytochemicals provide crucial sources for novel agents/drugs and resources for tumor therapy. Applying the small-molecule inhibitors (SMIs)/phytochemicals has led to potent preclinical discoveries in various human tumor preclinical models, including lung cancer. In this review, we summarize recent information on the molecular mechanisms of the Bax/Bcl-2 cascade and EGFR pathway in NSCLC and target them for therapeutic implications. We further described the therapeutic potential of Bax/Bcl-2/EGFR SMIs, mainly those with more potent and selectivity, including gefitinib, EGCG, ABT-737, thymoquinone, quercetin, and venetoclax. In addition, we explained the targeting EGFR pathway and ongoing in vitro and in vivo and clinical investigations in NSCLC. Exploration of such inhibitors facilitates the future treatment and management of NSCLC.
Since the original discovery of stem cells, a new era of promising results has emerged in the clinical application of stem cells for the treatment of several important diseases, including cancer and autoimmune diseases. The plentiful research on stem cells during the past decades has provided significant information on the developmental, morphological, and physiological processes that govern tissue and organ formation, maintenance, and regeneration; cellular differentiation; molecular processes; and tissue homeostasis. In this review, we present the history of the use of stem cells in different clinical applications. Furthermore, we discuss the various therapeutic options for stem cells in cancer, followed by the role of stem cells in the treatment of autoimmune disorders. Additionally, we highlight the risks of and obstacles to the application of stem cells in clinical practice. Ultimately, we show future perspectives in stem cell use, with an aim to improve the clinical usefulness of stem cells.
Herein, we evaluated the association of the Toll-like receptor 6 (TLR6) single nucleotide polymorphisms (SNPs) rs3796508 (Val327Met) and rs5743810 (Ser249Pro) with breast cancer (BC) susceptibility in Saudi Arabian women, using in silico analysis. We found no significant differences in genotypic and allelic frequencies for rs3796508 between the BC patients (n = 127) and healthy individuals (n = 116). However, 86% of the BC patients, versus 98% of the healthy controls, carried the rs5743810 Pro allele (OR = 0.103, CI = 0.036–0.293, P = 0.00001). Advanced analysis based on the comparison of the estrogen receptor (ER)-positive and -negative patients with the healthy controls indicated a significant association between rs5743810 allelic frequency and BC risk protection (OR = 0.100, CI = 0.034–0.297, P = 0.00001 for ER+ BC cases; OR = 0.102, CI = 0.033–0.318, P = 0.00001 for ER−BC cases). Furthermore, rs5743810 was associated with BC risk protection at either above or below 48 years of age at diagnosis (OR = 0.101, CI = 0.022–0.455, P = 0.00037 for age ≤48 years; OR = 0.120, CI = 0.028–0.519, P = 0.00087 for age >48 years). Such associations were not found for rs3796508. In silico analysis indicated that these SNPs had neutral effects within the TLR6 structure, confirming the protective role of rs5743810. Our findings therefore suggest a strong association between rs5743810 and protection against BC risk in Saudi Arabian women. Importantly, the rs5743810 Pro allele could be a potential BC diagnostic biomarker in this ethnic population.
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