Cell can integrate the caspase family and mammalian target of rapamycin (mTOR) signaling in response to cellular stress triggered by environment. It is necessary here to elucidate the direct response and interaction mechanism between the two signaling pathways in regulating cell survival and determining cell fate under cellular stress. Members of the caspase family are crucial regulators of inflammation, endoplasmic reticulum stress response and apoptosis. mTOR signaling is known to mediate cell growth, nutrition and metabolism. For instance, over-nutrition can cause the hyperactivation of mTOR signaling, which is associated with diabetes. Nutrition deprivation can inhibit mTOR signaling via SH3 domain-binding protein 4. It is striking that Ras GTPase-activating protein 1 is found to mediate cell survival in a caspase-dependent manner against increasing cellular stress, which describes a new model of apoptosis. The components of mTOR signaling-raptor can be cleaved by caspases to control cell growth. In addition, mTOR is identified to coordinate the defense process of the immune system by suppressing the vitality of caspase-1 or regulating other interferon regulatory factors. The present review discusses the roles of the caspase family or mTOR pathway against cellular stress and generalizes their interplay mechanism in cell fate determination.

Lung cancer remains the leading cause of cancer death worldwide. Late diagnosis, chemoresistance, and metastasis are the main reasons for the high mortality rate of lung cancer. Therefore, the development of other treatments is urgent. Cediranib (CED), a vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, shows promising antitumour activities in various cancers including lung cancer. Here, we explored the effects and the underlying molecular mechanism of CED on non‐small‐cell lung cancer (NSCLC) cell line A549 cells in vitro. Our results show that CED could inhibit A549 cell proliferation and cloning formation. Meanwhile, G1 phase cell cycle arrest was also found, as featured by the increased proportion of G1 phase cells as well as the reduction of G1 phase relative proteins CDK4/cyclin D1 and CDK2/cyclin E. Moreover, the ratio of LC3‐II/LC3‐I was elevated significantly in CED‐treated groups compared with the controls. Furthermore, the expression of p‐Akt, p‐P38, p‐Erk1/2, and p‐mTOR proteins was decreased obviously in the treatment groups. These results suggest that CED could induce apoptosis and G1 phase cell cycle arrest in A549 cells. Meanwhile, CED may induce autophagy through MAPK/Erk1/2 and Akt/mTOR signal pathway in A549 cells.

Nuclear medicine therapy offers a promising approach for tumor treatment, as the energy emitted during radionuclide decay causes irreparable damage to tumor cells. Notably, α-decay exhibits an even more significant destructive potential. By conjugating α-nuclides with antibodies or small-molecule inhibitors, targeted alpha therapy (TAT) can enhance tumor destruction while minimizing toxic side effects, making TAT an increasingly attractive antineoplastic strategy. Astatine-211 (²¹¹At) and actinium-225 (²²⁵Ac) have emerged as highly effective agents in TAT due to their exceptional physicochemical properties and biological effects. In this review, we highlight the applications of ²¹¹At-/²²⁵Ac-radiopharmaceuticals, particularly in specific tumor targets, such as prostate-specific membrane antigen (PSMA) in prostate cancers, cluster of differentiation (CD) in hematological malignancies, human epidermal growth factor receptor-2 (HER2) in ovarian cancers, and somatostatin receptor (SSTR) in neuroendocrine tumors. We synthesize the progress from preclinical and clinical trials to provide insights into the promising potential of ²¹¹At-/²²⁵Ac-radiopharmaceuticals for future treatments.

Objective: Patients receiving carbon-ion radiation therapy and astronauts exploring outer space are inevitably exposed to heavy ion radiation. The aim of this study was to develop radioprotectors to minimize the injuries induced by carbon ion radiation. Methods: Heat-killed Salmonella Typhimurium (HKST) was administered to mice by gavage prior to irradiation with a ¹²C⁶⁺ heavy ion accelerator. Hematoxylin and eosin staining and immunofluorescence TdT-mediated dUTP Nick-End Labeling staining were used to assess the radioprotective effect of HKST on organ damage and levels of apoptosis, respectively, in mice. To investigate the mechanism underlying the radioprotective effect of HKST, levels of the pro-apoptotic proteins BAX and caspase 3 as well as interferon-regulatory factor (IRF) 3/7 in the femur, testis and intestine were assessed using immunofluorescence. Results: Injuries induced by carbon ion radiation were significantly eased by pretreatment with HKST. Both apoptosis and high expression levels of pro-apoptotic proteins induced by heavy ion radiation were inhibited by HKST pretreatment. The radioprotective effect of HKST was associated with stimulation of Toll-like receptor signaling mediated by enhanced IRF3 and IRF7 signaling. Conclusion: HKST was an effective radioprotector alleviating damage to multiple organs caused by heavy ion radiation.

Cripto-1, a glycoprotein and key member of the epidermal growth factor-Cripto-1-FRL-1-Cryptic family, has garnered significant attention in cancer research due to its dual roles in embryonic development and tumor progression. The central role of Cripto-1 in regulating signaling pathways that govern cell behavior positions it as a promising target for enhancing diagnostic precision and therapeutic efficacy in cancer management. This mini-review explores the role of Cripto-1 in cancer biology, focusing on its involvement in key oncogenic pathways such as cell proliferation, migration, angiogenesis, and the maintenance of cancer stem cells (CSCs). Cripto-1 supports CSC self-renewal and contributes to treatment resistance. The review also examines recent advances in Cripto-1-targeted therapy, including monoclonal antibodies, small molecule inhibitors, and early-phase clinical trials, highlighting their therapeutic efficacy and safety profile. By synthesizing these findings, this review offers a comprehensive understanding of Cripto-1’s clinical relevance and provides new insights into its potential to improve diagnostic accuracy and therapeutic outcomes in cancer management.