^
5d
Head and neck tumor organoid biobank for modelling individual responses to radiation therapy according to the TP53/HPV status. (PubMed, J Exp Clin Cancer Res)
Our results highlight the translational value of the head and neck organoid models not only for patient stratification but also for mechanistic validation of therapy responsiveness of specific cancer drivers.
Journal
|
TP53 (Tumor protein P53)
|
TP53 mutation
|
Nutlin-3
7d
The role of HM13 expression and its relationship to PI3K/Akt and p53 signaling pathways in colorectal cancer. (PubMed, Tissue Cell)
Additionally, the administration of LY294003 and nutlin-3 effectively inhibits proliferation and migration, while promoting apoptosis in HCT116 cells (P<0.001)...Also, shHM13 decreased the level of p-PI3K/PI3K and p-AKT/AKT, upregulated p53 and p21 activities. It can thus be concluded that HM13 might be a novel oncogene in CRC and regulates proliferation, migration and apoptosis by modulating the PI3K/Akt and p53 signaling pathways.
Journal
|
CDKN1A (Cyclin-dependent kinase inhibitor 1A)
|
Nutlin-3
11d
Engineering Iridium Nanoclusters for Boosting Ferroptotic Cell Death by Regulating GPX4 and p53 Functions. (PubMed, Adv Healthc Mater)
Herein, a ferroptosis-inducing nanomedicine is developed that integrates nutlin-3 with iridium oxide nanoclusters (NUT-IrOx NCs) for enhanced ferroptosis-driven multimodal therapeutic efficacy in colorectal cancer (CRC)...This dual-pronged approach demonstrates robust anticancer therapeutic effects with favorable biocompatibility in both in vitro and in vivo CRC models. This study provides an effective strategy that highlights the benefits of inhibiting of GSH/GPX4 by activating multiple ferroptosis regulatory pathways, providing an alternative therapeutic avenue for CRC treatment.
Journal
|
GPX4 (Glutathione Peroxidase 4) • SLC7A11 (Solute Carrier Family 7 Member 11)
|
Nutlin-3
12d
A CEBPB/IL-1β/TNF-α Feedback Loop Drives Drug Resistance to Venetoclax and MDM2 Inhibitors in Monocytic Leukemia. (PubMed, Blood)
A combination of venetoclax/ idasanutlin with inhibitors that block IL-1/TNF-α pathway, demonstrate synergistic cytotoxicity in M4/M5 AML. As such, we uncovered a targetable positive feedback loop involving CEBPB, IL-1/TNF-α, and monocyte differentiation in M4/M5 leukemia, which promotes both intrinsic and extrinsic drug resistance, along with drug-induced protection against venetoclax and MDM2 inhibitors.
Journal
|
TP53 (Tumor protein P53) • MCL1 (Myeloid cell leukemia 1) • TNFA (Tumor Necrosis Factor-Alpha) • CASP3 (Caspase 3) • BCL2A1 (BCL2 Related Protein A1) • CASP6 (Caspase 6, apoptosis-related cysteine peptidase) • IL1B (Interleukin 1, beta)
|
TP53 wild-type
|
Venclexta (venetoclax) • idasanutlin (RG7388)
14d
MDM2 inhibitors induce apoptosis by suppressing MDM2 and enhancing p53, Bax, Puma and Noxa expression levels in imatinib‑resistant chronic myeloid leukemia cells. (PubMed, Biomed Rep)
NSC-66811 and Nutlin-3, MDM2 inhibitors, increased the percentage of Annexin-positive cells in K562/IR cells by 43 and 62% at concentrations of 10 and 25 µM, respectively. Additionally, pifithrin-α, a p53 inhibitor, suppressed MDM2 inhibitor-induced cell death in K562/IR cells. Overall, the findings of the present study highlight the therapeutic potential of MDM2 inhibitors for imatinib-resistant CML.
Journal
|
ABL1 (ABL proto-oncogene 1) • MDM2 (E3 ubiquitin protein ligase) • BAX (BCL2-associated X protein) • CASP3 (Caspase 3) • PMAIP1 (Phorbol-12-Myristate-13-Acetate-Induced Protein 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • ANXA5 (Annexin A5) • BBC3 (BCL2 Binding Component 3) • UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5)
|
imatinib • Nutlin-3
19d
A window-of-opportunity trial reveals mechanisms of response and resistance to navtemadlin in patients with recurrent glioblastoma. (PubMed, Sci Transl Med)
We also observed up-regulation of oligodendrocyte differentiation genes with navtemadlin treatment and enrichment of oligodendrocyte transcription factor 2 (OLIG2)-positive cells at relapse, suggesting an unexplored mechanism of navtemadlin tolerance in GBM. Overall, these results indicated that clinically achievable doses of navtemadlin exert pharmacodynamic effects on GBM and suggest that combined treatment with temozolomide may be a route to more durable survival benefits.
Clinical • Journal
|
TP53 (Tumor protein P53) • OLIG2 (Oligodendrocyte Transcription Factor 2)
|
TP53 mutation • TP53 wild-type
|
temozolomide • navtemadlin (KRT-232)
26d
Pharmacological Inhibition of MDM2 Induces Apoptosis in p53-Mutated Triple-Negative Breast Cancer. (PubMed, Int J Mol Sci)
We here selected the clinical-stage MDM2 inhibitors Idasanutlin and Milademetan and investigated their anti-tumoral effects in TNBC. This effect was observed despite an inactivating p53 mutation and was apparently independent of p53 expression. Our data suggest that MDM2 is a promising target in TNBC and clinical-stage MDM2 inhibitors should be further evaluated for their potential therapeutic application.
Journal
|
CASP3 (Caspase 3) • CASP7 (Caspase 7)
|
TP53 mutation • TP53 wild-type
|
milademetan (RAIN-32) • idasanutlin (RG7388)
28d
ALLIANCE-ABTC-1604: Testing the Ability of AMG 232 (KRT 232) to Get Into the Tumor in Patients With Brain Cancer (clinicaltrials.gov)
P1, N=32, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting | N=86 --> 32 | Trial completion date: Dec 2024 --> Feb 2026
Enrollment closed • Enrollment change • Trial completion date
|
TP53 (Tumor protein P53) • MGMT (6-O-methylguanine-DNA methyltransferase)
|
TP53 wild-type
|
navtemadlin (KRT-232)
1m
SPC25 upregulates CCND1 to promote the progression of esophageal squamous cell carcinoma by inhibiting MDM2-mediated E2F1 ubiquitination. (PubMed, Transl Oncol)
Collectively, we demonstrated that the aberrant expression of SPC25 inhibited E2F1 ubiquitination and promoted CCND1 expression, thus accelerating the progression of ESCC. These findings propose novel insights into the role of SPC25 in ESCC and provide potential therapeutic strategies for targeting SPC25 in ESCC patients.
Journal
|
CCND1 (Cyclin D1) • E2F1 (E2F transcription factor 1)
1m
LB-SA53-101: Safety and Preliminary Efficacy of SA53-OS in Patients With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
P1/2, N=70, Not yet recruiting, Lamassu Bio Inc | Trial completion date: Jun 2028 --> Dec 2028 | Initiation date: Sep 2024 --> Feb 2025 | Trial primary completion date: Aug 2025 --> Feb 2026
Trial completion date • Trial initiation date • Trial primary completion date
1m
Targeting the MDM2-p53 Interaction with Siremadlin: A Promising Therapeutic Strategy for Treating TP53 Wild-Type Chronic Lymphocytic Leukemia. (PubMed, Cancers (Basel))
The results underline the importance of TP53 status in predicting treatment efficacy and highlight the potential of HDM201 as a valuable addition to explore in CLL therapy. Future research should focus on identifying additional biomarkers of response and exploring the optimal way to include HDM201 in combination therapies to improve treatment outcomes in CLL.
Journal
|
TP53 (Tumor protein P53)
|
TP53 mutation • TP53 wild-type
|
siremadlin (HDM201)
1m
Ezetimibe Anticancer Activity via the p53/Mdm2 Pathway. (PubMed, Biomedicines)
Thus, Ezetimibe is probably active against cancers that overexpress Mdm2. Moreover, inhibitors of RBBP6 may be combined with Ezetimibe for effective anticancer activity. Due to poor oral bioavailability, Ezetimibe must be administered parenterally for cancer treatment.
Journal
|
TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase)
|
idasanutlin (RG7388) • RG7112
2ms
GATA2 links stemness to chemotherapy resistance in acute myeloid leukemia. (PubMed, Blood)
Knockdown of Rassf4 in Gata2 low cells resulted in doxorubicin or nutlin-3 resistance. We discovered a previously unappreciated role for GATA2 in dampening p53-mediated apoptosis via transcriptional regulation of RASSF4, a modulator of MDM2. This role for GATA2 directly links the expression of a stemness associated transcription factor to chemotherapy resistance.
Journal
|
KMT2A (Lysine Methyltransferase 2A) • KMT2C (Lysine Methyltransferase 2C) • GATA2 (GATA Binding Protein 2)
|
doxorubicin hydrochloride • Nutlin-3
2ms
CAPS: APG-115 in Salivary Gland Cancer Trial (clinicaltrials.gov)
P1/2, N=41, Active, not recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jun 2025
Trial completion date • Trial primary completion date
|
carboplatin • alrizomadlin (APG-115)
2ms
A Study of Siremadlin in Combination With Venetoclax Plus Azacitidine in Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Chemotherapy. (clinicaltrials.gov)
P1, N=14, Terminated, Novartis Pharmaceuticals | Consequently, enrollment for Part 2 did not commence. This decision was not influenced by any safety concerns.
Trial termination
|
TP53 (Tumor protein P53)
|
TP53 mutation
|
Venclexta (venetoclax) • azacitidine • siremadlin (HDM201)
2ms
Study of ASTX295 in Patients With Solid Tumors With Wild-Type p53 (clinicaltrials.gov)
P1/2, N=106, Terminated, Taiho Oncology, Inc. | Trial completion date: Jun 2025 --> Aug 2024 | Active, not recruiting --> Terminated; Sponsor Decision
Trial completion date • Trial termination
|
TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase)
|
TP53 wild-type • MDM2 amplification
|
ASTX295
2ms
Tumor hypoxia evidences the differential regulation of Mdm2-p53 axis by PTEN in tumor derived vs. normal endothelial cells. (PubMed, Sci Rep)
In conclusion, the PTEN-mediated control of pathological angiogenesis occurs by modulation of Mdm2/p53 interaction in the context of breast tumor microenvironment. PTEN emerges as a potential therapeutic target for normalizing tumor vessels in breast cancer treatment strategies.
Journal
|
PTEN (Phosphatase and tensin homolog) • MDM2 (E3 ubiquitin protein ligase)
|
PTEN expression
|
Nutlin-3
2ms
Anlotinib enhances the pro-apoptotic effect of APG-115 on acute myeloid leukemia cell lines by inhibiting the P13K/AKT signaling pathway. (PubMed, Leuk Res)
In vivo and in vitro experimental have shown that APG-115 combined with anlotinib can promote AML cells apoptosis and inhibit the progression of disease is independent of the p53 status.
Preclinical • Journal
|
ANXA5 (Annexin A5)
|
Focus V (anlotinib) • alrizomadlin (APG-115)
3ms
Trial termination
|
TP53 (Tumor protein P53)
|
TP53 wild-type
|
Venclexta (venetoclax) • cytarabine • cyclophosphamide • topotecan • idasanutlin (RG7388) • fludarabine IV
3ms
p53 and the E3 Ubiquitin Ligase MDM2 in Glaucomatous Lamina Cribrosa Cells. (PubMed, Int J Mol Sci)
MTT-assay showed equivocal cellular viability in NLC/GLC cells with/without RG-7112 treatment. Our data suggests that proliferation and the ubiquitin-proteasomal pathway are dysregulated in GLC cells, with MDM2-led p53 protein degradation negatively impacting its protective role.
Journal
|
MDM2 (E3 ubiquitin protein ligase) • CASP3 (Caspase 3) • COL1A1 (Collagen Type I Alpha 1 Chain)
|
TP53 expression
|
RG7112
4ms
Dominant-negative TP53 mutations potentiated by the HSF1-regulated proteostasis network. (PubMed, bioRxiv)
Specifically, we apply quantitative deep mutational scanning of p53 to assess how HSF1 activation shapes the mutational pathways by which p53 can escape cytotoxic pressure conferred by the small molecule nutlin-3, which is a potent antagonist of the p53 negative regulator MDM2...These results indicate that chronic HSF1 activation profoundly shapes the oncogenic mutational landscape, preferentially supporting the acquisition of cancer-associated substitutions that are biophysically destabilizing. Along with providing the first experimental and quantitative insights into how HSF1 influences oncoprotein mutational spectra, these findings also implicate HSF1 inhibition as a strategy to reduce the accessibility of mutations that drive chemo-therapeutic resistance and metastasis.
Journal
|
TP53 (Tumor protein P53) • HSF1 (Heat Shock Transcription Factor 1)
|
TP53 mutation
|
Nutlin-3
4ms
Recapitulating the adenoma-carcinoma sequence by selection of four spontaneous oncogenic mutations in mismatch-repair-deficient human colon organoids. (PubMed, Nat Cancer)
Here, we demonstrate that long-term culture of mismatch-repair-deficient organoids allows the selection of spontaneous oncogenic mutations through the sequential withdrawal of Wnt agonists, epidermal growth factor (EGF) agonists and the bone morphogenetic protein (BMP) antagonist Noggin, while TP53 mutations were selected through the addition of Nutlin-3...Quadruple-pathway (Wnt, EGF receptor, p53 and BMP) mutant organoids formed solid tumors upon xenotransplantation. This demonstrates that carcinogenesis can be recapitulated in a DNA repair-mutant background through in vitro selection that targets four consecutive cancer pathways.
Journal • Mismatch repair
|
NRAS (Neuroblastoma RAS viral oncogene homolog) • ACVR2A (Activin A Receptor Type 2A)
|
TP53 mutation • MSI-H/dMMR
|
Nutlin-3
5ms
Enhanced Anti-Melanoma Activity of Nutlin-3a Delivered via Ethosomes: Targeting p53-Mediated Apoptosis in HT144 Cells. (PubMed, Cells)
Overall, nutlin-3a delivery using ethosomes appears to be a significantly effective means for upregulating the p53 pathway and downregulating active Notch-1, while also taking advantage of their unexpected ability to reduce cellular migration. The findings of this study could pave the way for the development of specific nutlin-3a-loaded ethosome-based medicinal products for cutaneous use.
Journal
|
NOTCH1 (Notch 1) • NICD (NOTCH1 intracellular domain) • TNFRSF10B (TNF Receptor Superfamily Member 10b)
|
TP53 mutation • TP53 wild-type • NICD expression
|
Nutlin-3
5ms
New P2 trial
|
BAP1 (BRCA1 Associated Protein 1)
|
alrizomadlin (APG-115)
5ms
An update patent review of MDM2-p53 interaction inhibitors (2019-2023). (PubMed, Expert Opin Ther Pat)
Despite twenty years of intensive studies after the discovery of the first-in-class small-molecule inhibitor, Nutlin-3, no drugs targeting MDM2-p53 interaction have reached the market. Nevertheless, more than ten compounds are still evaluated in clinics, both as standalone drugs and in combinations with other targeted therapies or standard chemotherapy agents, including two inhibitors in phase 3 studies and two compounds granted orphan-drug/fast-track designation by the FDA.
Review • Journal
|
MDM4 (The mouse double minute 4)
|
TP53 mutation
|
Nutlin-3
5ms
Effects of Mdm2 Inhibitors on Cellular Viability of Breast Cancer Cell Lines HP100, MCF7. (PubMed, Bratisl Lek Listy)
Our research concluded that Nutlin 3 has a superior effect over Yh239-EE and Miladometan in treating Breast cancer; moreover, the combination group has shown to be more effective than treatment with Doxorubicin or MDM2 inhibitors alone. Interesting information is that Doxorubicin also causes an increase in P53 levels. This result provided us with a promising therapeutic strategy for the treatment of breast cancer. However, more research is required to be conducted on more types of cell lines and in human or animal models (Tab. 4, Fig. 8, Ref. 33). Text in PDF www.elis.sk Keywords: breast cancer, Miladometan, cell viability, proliferation, therapeutic strategy.
Preclinical • Journal
|
MDM2 (E3 ubiquitin protein ligase)
|
TP53 expression
|
doxorubicin hydrochloride • milademetan (RAIN-32) • Nutlin-3
5ms
p27 Cell Cycle Inhibitor and Survival in Luminal-Type Breast Cancer: Gene Ontology, Machine Learning, and Drug Screening Analysis. (PubMed, J Breast Cancer)
The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer.
Journal • Machine learning
|
ER (Estrogen receptor) • PGR (Progesterone receptor) • CD8 (cluster of differentiation 8) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • CDKN1B (Cyclin dependent kinase inhibitor 1B)
|
CDKN1B expression
|
serdemetan (JNJ-26854165) • voxtalisib (SAR245409)
6ms
Targeting MDM2-mediated suppression of p53 with idasanutlin: a promising therapeutic approach for acute lymphoblastic leukemia. (PubMed, Invest New Drugs)
In this research, RG7388 was investigated with pre-clinical methods in ALL cells as a novel treatment strategy. This study suggests further functional research and in-vivo evaluation, and it highlights the prospect of treating p53-functional ALL with MDM2 inhibitors.
Journal
|
CASP3 (Caspase 3) • CASP7 (Caspase 7)
|
TP53 mutation • TP53 wild-type • TP53 expression
|
idasanutlin (RG7388)
6ms
Analysis of the role of CHPF in colorectal cancer tumorigenesis and immunotherapy based on bioinformatics and experiments. (PubMed, Discov Oncol)
CHPF could promote the proliferation and migration of CRC cells and lead to poor prognosis, possibly through wnt pathways as well as changes in TME. Patients with high expression of CHPF had poor efficacy in immunotherapy, which might be related to Tregs cell infiltration. Above all, it might offer more reliable guidance for future immunotherapy.
Journal • Tumor mutational burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
|
TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PD-1 (Programmed cell death 1) • CHPF (Chondroitin Polymerizing Factor)
|
MSI-H/dMMR
|
Mekinist (trametinib) • serdemetan (JNJ-26854165) • telatinib (BAY 57- 9352)
6ms
HDM201 in Combination With MBG453 or Venetoclax in Patients With Acute Myeloid Leukemia (AML) or High-risk Myelodysplastic Syndrome (MDS) (clinicaltrials.gov)
P1, N=52, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; Business decision
Trial termination • Combination therapy
|
TP53 (Tumor protein P53)
|
TP53 wild-type
|
Venclexta (venetoclax) • sabatolimab (MBG453) • siremadlin (HDM201)
6ms
Integrated stress response (ISR) activation and apoptosis through HRI kinase by PG3 and other p53 pathway-restoring cancer therapeutics. (PubMed, Oncotarget)
We compare activation of p53 target genes by novel compounds PG3 and PG3-Oc, that activate p53-target genes in a p53-independent manner, and four mutant p53-activating compounds while Nutlin-3a is used as negative control...We provide a novel mechanism engaged by PG3 to induce cell death via the HRI/ATF4/PUMA axis. Our results provide unique insights into the mechanism of action of PG3 as a novel cancer therapeutic targeting p53 pathway-like tumor suppression.
Journal
|
GDF15 (Growth differentiation factor 15) • CASP8 (Caspase 8) • ATF4 (Activating Transcription Factor 4) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • CASP10 (Caspase 10)
|
TP53 mutation • TP53 expression
|
Nutlin-3
6ms
Trial completion • Combination therapy
|
GDF15 (Growth differentiation factor 15)
|
Ninlaro (ixazomib) • idasanutlin (RG7388)
6ms
MDM2 inhibitors in cancer immunotherapy: Current status and perspective. (PubMed, Genes Dis)
In addition, we summarized preclinical and clinical findings on the use of MDM2 inhibitors in combination with immunotherapy in tumors with MDM2 overexpression or amplification. The results reveal that the inhibition of MDM2 could be a promising strategy for enhancing immunotherapy.
Review • Journal • PD(L)-1 Biomarker • IO biomarker
|
MDM2 (E3 ubiquitin protein ligase)
|
MDM2 overexpression
6ms
Testing a New Chemotherapy Drug, KRT-232 (AMG-232) in Combination With Decitabine and Venetoclax in Patients With Acute Myeloid Leukemia (clinicaltrials.gov)
P1, N=58, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting
Enrollment closed • Combination therapy
|
TP53 (Tumor protein P53) • CD4 (CD4 Molecule)
|
TP53 mutation • Chr del(17p) • TP53 wild-type
|
Venclexta (venetoclax) • decitabine • navtemadlin (KRT-232)
6ms
Study of ASTX295 in Patients With Solid Tumors With Wild-Type p53 (clinicaltrials.gov)
P1/2, N=106, Active, not recruiting, Taiho Oncology, Inc. | N=250 --> 106
Enrollment change • Metastases
|
TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase)
|
TP53 wild-type • MDM2 amplification
|
ASTX295
6ms
BH3-mimetics or DNA-damaging agents in combination with RG7388 overcome p53 mutation-induced resistance to MDM2 inhibition. (PubMed, Apoptosis)
This mutation abated its transcriptional activity via destabilization of the tetrameric p53-DNA complex and was observed in many cancer types. Finally, we found that Cisplatin and various BH3-mimetics could enhance RG7388-mediated apoptosis in RG7388-resistant neuroblastoma cells, thereby partially overcoming resistance to MDM2 inhibition.
Journal • Combination therapy
|
TP53 (Tumor protein P53)
|
cisplatin • idasanutlin (RG7388)
6ms
RPL22L1 is a novel biomarker for prognosis and immune infiltration in lung adenocarcinoma, promoting the growth and metastasis of LUAD cells by inhibiting the MDM2/P53 signaling pathway. (PubMed, Aging (Albany NY))
Notably, the expression of RPL22L1 exhibited significant negative correlations with 1-BET-762, Trametinib, and WZ3105 in LUAD...Significantly increased expression of RPL22L1 was noted in LUAD cell lines, where it was found to enhance the growth and metastasis of LUAD cells by suppressing the MDM2/P53 signaling pathway. Therefore, RPL22L1 may serve as a promising prognostic biomarker and therapeutic target for patients with LUAD.
Journal • Tumor mutational burden
|
RPL22L1 (Ribosomal Protein L22 Like 1) • RPL22 (Ribosomal Protein L22)
|
Mekinist (trametinib)
6ms
Surgical window of opportunity trial reveals mechanisms of response and resistance to navtemadlin (KRT-232) in patients with recurrent glioblastoma. (PubMed, medRxiv)
However, combining navtemadlin with temozolomide increased apoptotic rates while sparing normal bone marrow cells in vitro, which in return underwent reversible growth arrest. Tissue sampling during this clinical trial allowed us to assess mechanisms of response and resistance associated with navtemadlin treatment in recurrent GBM. We report that clinically achievable doses of navtemadlin induce pharmacodynamic effects in tumor tissue, and suggest combinations with standard-of-care chemotherapy for durable clinical benefit.
Journal
|
TP53 (Tumor protein P53)
|
temozolomide • navtemadlin (KRT-232)
6ms
Synthetic lethality of combined ULK1 defection and p53 restoration induce pyroptosis by directly upregulating GSDME transcription and cleavage activation through ROS/NLRP3 signaling. (PubMed, J Exp Clin Cancer Res)
Our research demonstrates that ULK1 deficiency can synergize with MDM2 inhibitors to induce pyroptosis. p53 plays a direct role in activating GSDME transcription, while ULK1 deficiency triggers upregulation of the ROS-NLRP3 signaling pathway, leading to GSDME cleavage and activation. These findings underscore the pivotal role of p53 in determining pyroptosis and provide new avenues for the clinical application of p53 restoration therapies, as well as suggesting potential combination strategies.
Journal • Synthetic lethality
|
MDM2 (E3 ubiquitin protein ligase) • NLRP3 (NLR Family Pyrin Domain Containing 3) • GSDME (Gasdermin E)
|
alrizomadlin (APG-115)
6ms
Astilbin Induces Apoptosis in Oral Squamous Cell Carcinoma through p53 Reactivation and Mdm-2 Inhibition. (PubMed, Dokl Biochem Biophys)
This was followed by the induction of mitochondrial intrinsic apoptosis via the activation of caspases 9 and 3, cleavage of PARP, and the suppression of pro-apoptotic Bid. Astilbin-induced p53-mediated apoptosis in OSCC cells as herbal medicinal ingredients.
Journal • PARP Biomarker
|
CASP9 (Caspase 9)
|
RITA
7ms
Trial suspension • Combination therapy
|
TP53 (Tumor protein P53) • CD4 (CD4 Molecule)
|
Venclexta (venetoclax) • decitabine • navtemadlin (KRT-232)