Comprehensive review of Bcl‐2 family proteins in cancer apoptosis: Therapeutic strategies and promising updates of natural bioactive compounds and small molecules

Iksen,; Witayateeraporn, Wasita; Hardianti, Besse; Pongrakhananon, Varisa

doi:10.1002/ptr.8157

Cited by 3 publications

References 232 publications

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Decoding the molecular landscape: A novel prognostic signature for uveal melanoma unveiled through programmed cell death-associated genes

Liu,

Yu,

Lai

et al. 2024

Medicine

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Uveal melanoma (UM) is a rare but aggressive malignant ocular tumor with a high metastatic potential and limited therapeutic options, currently lacking accurate prognostic predictors and effective individualized treatment strategies. Public databases were utilized to analyze the prognostic relevance of programmed cell death-related genes (PCDRGs) in UM transcriptomes and survival data. Consensus clustering and Lasso Cox regression analysis were performed for molecular subtyping and risk feature construction. The PCDRG-derived index (PCDI) was evaluated for its association with clinicopathological features, gene expression, drug sensitivity, and immune infiltration. A total of 369 prognostic PCDRGs were identified, which could cluster UM into 2 molecular subtypes with significant differences in prognosis and clinicopathological characteristics. Furthermore, a risk feature PCDI composed of 11 PCDRGs was constructed, capable of indicating prognosis in UM patients. Additionally, PCDI exhibited correlations with the sensitivity to 25 drugs and the infiltration of various immune cells. Enrichment analysis revealed that PCDI was associated with immune regulation-related biological processes and pathways. Finally, a nomogram for prognostic assessment of UM patients was developed based on PCDI and gender, demonstrating excellent performance. This study elucidated the potential value of PCDRGs in prognostic assessment for UM and developed a corresponding risk feature. However, further basic and clinical studies are warranted to validate the functions and mechanisms of PCDRGs in UM.

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Decoding the molecular landscape: A novel prognostic signature for uveal melanoma unveiled through programmed cell death-associated genes

Liu,

Yu,

Lai

et al. 2024

Medicine

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Drug combinations with apoptosis pathway targeted agents alrizomadlin, pelcitoclax, and dasminapant in multi-cell type tumor spheroids

Coussens,

Dexheimer,

Silvers

et al. 2024

Preprint

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Apoptosis, or programmed cell death, plays a critical role in maintaining tissue homeostasis by eliminating damaged or abnormal cells. Dysregulation of apoptosis pathways is a hallmark of cancer, allowing malignant cells to evade cell death and proliferate uncontrollably. Targeting apoptosis pathways has emerged as a promising therapeutic strategy in cancer treatment, aiming to restore the balance between cell survival and death. In this context, the MDM2 inhibitor alrizomadlin, the Bcl-2/Bcl-xL inhibitor pelcitoclax, and the IAP family inhibitor dasminapant were evaluated both individually and in combination with standard of care and investigational anticancer small molecules with a spheroid model of solid tumors. The multi-cell type tumor spheroids were grown from endothelial cells and mesenchymal stem cells combined with human malignant cells that were either established or patient-derived cell lines from the NCI Patient- Derived Models Repository. The malignant cell lines were derived from a range of solid tumors including uterine carcinosarcoma, synovial sarcoma, rhabdomyosarcoma, soft tissue sarcoma, malignant fibrous histiocytoma, malignant peripheral nerve sheath tumor (MPNST), pancreas, ovary, colon, breast, and small cell lung cancer. Interactions were observed from combinations of the apoptosis pathway targeted agents. Additionally, interactions were observed from combinations of the apoptosis pathway targeted agents with other agents, including PARP inhibitors, the XPO1 inhibitor eltanexor, and the PI3K inhibitor copanlisib. Enhanced activity was also observed from combinations of the apoptosis pathway targeted agents with MAPK pathway targeted agents, including the MEK inhibitor cobimetinib as well as adagrasib and MRTX1133, which specifically target the KRAS G12C and G12D variants, respectively.SIGNIFICANCEMulti-cell type tumor spheroids grown from normal and patient-derived malignant cell lines were screened to identify potentially efficacious combinations with the investigational agents alrizomadlin, pelcitoclax or dasminapant that target cell death pathways. This article highlights novel combinations with FDA approved drugs including eltanexor, cobimetinib and copanlisib.

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Comprehensive review of Bcl‐2 family proteins in cancer apoptosis: Therapeutic strategies and promising updates of natural bioactive compounds and small molecules

Cited by 3 publications

References 232 publications

Decoding the molecular landscape: A novel prognostic signature for uveal melanoma unveiled through programmed cell death-associated genes

Decoding the molecular landscape: A novel prognostic signature for uveal melanoma unveiled through programmed cell death-associated genes

Drug combinations with apoptosis pathway targeted agents alrizomadlin, pelcitoclax, and dasminapant in multi-cell type tumor spheroids

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