Targeting the intrinsic apoptotic pathway regulated by B-cell lymphoma-2 (BCL-2) antiapoptotic proteins can overcome the evasion of apoptosis in cancer cells. BCL-2 inhibitors have evolved into an important means of treating cancers by inducing tumor cell apoptosis. As the most extensively investigated BCL-2 inhibitor, venetoclax is highly selective for BCL-2 and can effectively inhibit tumor survival. Its emergence and development have significantly influenced the therapeutic landscape of hematological malignancies, especially in chronic lymphocytic leukemia and acute myeloid leukemia, in which it has been clearly incorporated into the recommended treatment regimens. In addition, the considerable efficacy of venetoclax in combination with other agents has been demonstrated in relapsed and refractory multiple myeloma and certain lymphomas. Although venetoclax plays a prominent antitumor role in preclinical experiments and clinical trials, large individual differences in treatment outcomes have been characterized in real-world patient populations, and reduced drug sensitivity will lead to disease recurrence or progression. The therapeutic efficacy may vary widely in patients with different molecular characteristics, and key genetic mutations potentially result in differential sensitivities to venetoclax. The identification and validation of more novel biomarkers are required to accurately predict the effectiveness of BCL-2 inhibition therapy. Furthermore, we summarize the recent research progress relating to the use of BCL-2 inhibitors in solid tumor treatment and demonstrate that a wealth of preclinical models have shown promising results through combination therapies. The applications of venetoclax in solid tumors warrant further clinical investigation to define its prospects.

Multiple myeloma (MM) is an incurable plasma cell malignancy with a poor survival rate. Conventional chemotherapeutic agent‐induced adverse events, including toxicity, neuropathy or drug resistance, significantly decrease the patients' quality of life and can even lead to interruption of treatment. Therefore, novel therapeutic drugs and strategies are urgently needed to improve MM therapy and patient outcomes. Here, we show that solamargine (SM), a steroidal alkaloid glycoside isolated from a Chinese herb Solanum nigrum L., exhibits promising anti‐MM activity. In particular, SM suppressed the viability of MM cell lines (ARP‐1 and NCI‐H929) in a concentration‐ and time‐dependent manner, inducing apoptosis in these cells. RNA‐seq analysis showed that treatment with SM led to the upregulation of genes associated with cell death and autophagy in H929 cells. Further, we found that treatment with SM activated autophagy in the MM cells, as incubation with 3‐Methyladenine, an inhibitor of autophagy, significantly alleviated SM‐triggered apoptosis and inhibition of viability in MM cells. Interestingly, we also observed a synergistic effect between SM and bortezomib (BTZ), a common chemotherapeutic agent for MM, in both MM cells and human bone marrow CD138+ primary myeloma cells. We also confirmed the single‐agent efficacy of SM and the synergistic effects between SM and BTZ in an MM xenograft mouse model. Collectively, these findings indicate that SM exerts an anti‐MM effect, at least in part, by activating cell autophagy and reveal that SM alone or in combination with BTZ is a potential therapeutic strategy for treating MM.

Background: It remains largely unclear how education level, an important socioeconomic factor, affects prognoses for patients with gastric adenocarcinoma (GAC). We aimed to demonstrate the associations between education level and clinical outcomes in patients with GAC.Methods: We included a total of 30,409 patients diagnosed with GAC from the Surveillance, Epidemiology, and End Results 18 registry database. Education level, household income, unemployment rate, poverty rate, insurance status, and marital status were selected as sociodemographic variables for the comprehensive analysis. Cox and logistic regression models, Kaplan–Meier curves, and subgroup analyses were the primary statistical methods employed.Results: A low level of education was correlated with less income, higher unemployment rates, and higher poverty rates (all p < 0.001). The multivariate Cox analysis indicated that a high education level was significantly associated with superior overall survival rates and cancer-specific survival rates in patients with GAC (both p < 0.001). We also corroborated favorable survival outcomes by high education level within almost every clinical and demographic subgroup. Furthermore, chemotherapy combined with surgery could markedly prolong the survival for all patients, including patients of stage IV cancer (both p < 0.001). By using multivariable logistic models, patients in counties with high education levels had a higher probability of chemotherapy receipt (p < 0.001). Contrarily, those in the counties with low levels of education were less likely to receive chemotherapy or undergo surgery (p < 0.001).Conclusions: Education level was identified and confirmed as an independent predictor of treatment and survival for GAC patients. Efforts are needed to provide effective interventions for those whose educational status is adverse.

Hepatocellular carcinoma (HCC) is a major medical challenge due to its high incidence and poor prognosis. 5-Fluorouracil (5-FU), although extensively studied in the treatment of HCC and other solid tumors, has limited application as a first-line therapy for HCC due to its resistance and significant inter-patient variability. To address these issues, researchers have explored drug repurposing. One of our key findings in this endeavour was the potent anti-HCC effect of the natural product Salidroside (Sal) when co-administered with 5-FU. Sal was found to inhibit mitosis and promote cellular senescence in HCC cells via a mechanism distinct from 5-FU, specifically by inducing excessive mitophagy that led to cellular mitochondrial dysfunction. Importantly, YIPF5 was confirmed as a potential molecular target of Sal. This natural product modulated YIPF5-induced mitophagy and influenced both mitosis and senescence in HCC cells. The combination of Sal and 5-FU demonstrated significant therapeutic effects in a mouse HCC model. In conclusion, our study was not only in line with the innovative strategy of drug repurposing, but also important for drug design and natural product screening targeting the relevant pathways.

Objective: This study aimed to comprehensively investigate the relationship between the survival differences and socioeconomic status (SES) in patients with multiple myeloma (MM) and construct a predictive nomogram to assess clinical outcomes of MM patients.Methods: The Surveillance, Epidemiology, and End Results (SEER) census tract-level SES database provides two specialized attributes: SES index and rurality. Using this database, 37,819 patients diagnosed with MM between January 2007 and December 2016 were enrolled. We evaluated the effects of SES index on overall survival (OS) and myeloma-specific survival (MSS) using Kaplan-Meier curves and Cox regression analyses. Thereafter, we included 126 patients with MM from two independent medical centers in China and divided them into training (Center 1) and validation (Center 2) cohorts. Univariate and multivariate Cox analyses were used in the training cohort to construct a nomogram for predicting clinical outcomes. Nomogram performance was assessed using the area under the curve (AUC) and calibration curves.Results: In the SEER cohort, lower SES was significantly associated with worse OS rates and MSS rates (both P < 0.001). Multivariate analysis confirmed SES as an independent predictor of survival. Subgroup analysis indicated an increasing linear trend in survival benefits in non-Hispanic White, married, insured, and urban populations with increasing SES (all P < 0.001). In the training cohort, albumin, creatinine, rurality, and SES were confirmed as independent prognostic indicators. A nomogram for OS prediction was developed using these four factors, and it showed satisfactory discrimination and calibration. The 18- and 36-month AUC values of the nomogram were 0.79 and 0.82, respectively. Based on the total nomogram points, patients were categorized into two risk levels with good separation.Conclusion: SES strongly influences survival disparities in patients with MM. Our nomogram consisting of clinical and sociodemographic characteristics can potentially predict survival outcomes.