Thyagarajan Anita, Sirhan Zaid, Sahu Ravi P
Department of Pharmacology and Toxicology, Boonshoft School of Medicine at Wright State University, Dayton, OH 45435, USA.
Explor Drug Sci. 2025;3. doi: 10.37349/eds.2025.100883. Epub 2025 Jan 14.
The integration between the tumor-suppressive and oncogenic signaling pathways controls various cellular activities of cancer cells, including cell growth and apoptosis. While the activation of oncogenes fuels cancer progression and escape mechanisms, tumor suppressors regulate and counterbalance the negative effects of oncogenic signaling. Notably, phosphatase and tensin homolog (PTEN) constitute one of the important family members of tumor suppressor genes, which play critical roles in regulating the activities of tumor cells. Thus, an impaired, mutated, or loss of PTEN is associated with low survival or high tumor recurrence rates in cancer patients. Importantly, high tumor expression of a G-protein coupled platelet-activating factor-receptor (PAFR) is associated with increased tumor progression as well as decreased overall survival and poor prognosis in malignancies such as non-small cell lung cancer (NSCLC). Along similar lines, overactivation or mutations in epidermal growth factor receptor (EGFR) signaling are detected in various human malignancies and associated with poor prognosis. The goal of the current minireview was to highlight the significance of the mechanistic insights between the PTEN and PAFR as well as the PAFR and EGFR pathways in impacting cancer growth and/or efficacy of therapeutic agents in experimental model systems.
肿瘤抑制信号通路与致癌信号通路之间的整合控制着癌细胞的各种细胞活动，包括细胞生长和凋亡。虽然癌基因的激活推动癌症进展和逃逸机制，但肿瘤抑制因子调节并平衡致癌信号的负面影响。值得注意的是，磷酸酶和张力蛋白同源物（PTEN）是肿瘤抑制基因的重要家族成员之一，在调节肿瘤细胞活动中起关键作用。因此，PTEN功能受损、突变或缺失与癌症患者的低生存率或高肿瘤复发率相关。重要的是，G蛋白偶联血小板活化因子受体（PAFR）在肿瘤中的高表达与肿瘤进展增加以及非小细胞肺癌（NSCLC）等恶性肿瘤的总生存率降低和预后不良相关。同样，在各种人类恶性肿瘤中检测到表皮生长因子受体（EGFR）信号的过度激活或突变，并与预后不良相关。本综述的目的是强调在实验模型系统中，PTEN与PAFR以及PAFR与EGFR通路之间的机制见解在影响癌症生长和/或治疗药物疗效方面的重要性。
