Morusin induces CRC cell senescence via the DNMT1/CDK2/p53 axis, and renders the cells vulnerable to senolytic agents. This study not only broadens the development and utilization of morusin but also provides a novel sequential therapeutic strategy for combating CRC.

Pathway and perturbation analyses suggested that NCI-LYM-1 harbored a strong dependency on apoptotic pathways, which was confirmed by in vitro organoid testing with the BCL-2/BCL-xL inhibitor navitoclax (IC 50 : 0.27 µM) and the MCL-1 inhibitor AZD-5991 (IC 50 : 0.060 µM). Overall, NCI-LYM-1 recapitulates the clinical aggressiveness and heterogeneity of AVPC, providing a tractable platform to identify novel precision therapies.

P1/2, N=75, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

The B-cell lymphoma 2 (BCL-2) inhibitor venetoclax (VEN) in combination with hypomethylating agents (HMAs) has improved treatment outcomes for acute myeloid leukemia (AML) patients unfit for intensive chemotherapy and is increasingly used in the relapsed/refractory setting. Ex vivo treatment with the combination of navitoclax and SMAC mimetics further enhanced the eradication of VEN-HMA refractory blasts, although toxicity was also observed in healthy CD34+ cells. In conclusion, our integrative analysis identifies molecular signatures associated with primary VEN-HMA resistance and highlights BCL-2/BCL-XL inhibition and SMAC mimetics as therapeutic strategies to target resistance.

Brain irradiation induces liver proliferation, increased GFAP levels, and elevated ALT and AST activity, via mechanisms likely independent of senescence. Future investigation of blood GFAP levels is needed to determine whether the enhanced hepatic GFAP levels originate from the brain.

Finally, we show that a combination of irradiation with Navitoclax enhances cancer cell apoptosis in an orthotopic xenograft DMG model. Together, the data demonstrate that ionising irradiation leads to senescence induction in H3K27M-altered human DMG cell lines, making them particularly sensitive to apoptosis through Bcl-xL inhibition.

Our previous study demonstrated that cisplatin (CDDP) induced ESCC cell senescence, and senescent cells promoted the aggressive behaviors of neighboring cancer cells through the senescence-associated secretory phenotype (SASP). Mechanistically, the enhanced interaction between BCL-XL and pro-apoptotic effector protein BAX conferred apoptosis resistance in senescent ESCC cells, and ABT-263 treatment disrupted this interaction to activate apoptosis. Overall, our data indicate that CDDP-induced senescent ESCC cells could be eliminated using senolytic drugs that target BCL-XL, and thus senolytic therapy could be a potential effective strategy for improving chemotherapeutic efficacy in ESCC.

One signature distinguished neuroblastoma samples with sensitivity to navitoclax, a BCL2 family inhibitor...The combination of multiomics analysis and drug sensitivity profiling identified two signatures related to drug sensitivity in pediatric solid tumors, contributing to the advancement of functional precision medicine and personalized treatment strategies. This article is part of a special series: Driving Cancer Discoveries with Computational Research, Data Science, and Machine Learning/AI .

The senolytic Navitoclax targeted only a subset of senescent cells. Thus, the diversity of senescent cells driven by epigenetic changes can generate divergent outcomes. UHRF1 overexpression in zebrafish hepatocytes induces DNA damage leading to Atm-tp53-dependent senescence with UHRF1 levels dictating whether hepatocytes remain senescent, escape, or undergo senolytic elimination.

P1, N=6, Active, not recruiting, Thomas Jefferson University | Phase classification: P1/2 --> P1

Conversely, the high-risk group exhibited distinct genomic features and was predicted to be more sensitive to specific targeted agents, including Navitoclax and Sorafenib. We identified and validated a novel 7-gene prognostic signature derived from a subpopulation of EGFR-TKI-resistant macrophages. This signature accurately predicts patient survival, offers insights into the molecular mechanisms of therapy resistance in HCC, and provides a promising tool for improved patient stratification and the development of personalized treatment strategies.

Carfilzomib synergized with BCL2 family protein inhibitors (navitoclax or AZD5991), suggesting that drug combinations could be used to reduce the dose of each drug to minimize toxicity. Notably, thymic carcinomas differed from squamous cell carcinomas in other organs by higher levels of β5i (PSMB8) and constitutive proteasome β5 (PSMB5). We hypothesize that TC (and probably many TH) are uniquely suited for treatment with proteasome inhibitors alone or in combination with selective BH3 mimetics.