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DRUG:

navitoclax (ABT 263)

i
Other names: ABT 263, ABT-263, RG 7423, RG7423, RG 7433, RG7433
Company:
AbbVie
Drug class:
Bcl2 inhibitor, Bcl-xL inhibitor, Bcl-w inhibitor
Related drugs:
4d
Exactis-03: Combination of Olaparib and Navitoclax in Women with HGSC and TNBC (clinicaltrials.gov)
P1, N=36, Active, not recruiting, Sunnybrook Health Sciences Centre | Recruiting --> Active, not recruiting | Trial primary completion date: Apr 2024 --> Mar 2025
Enrollment closed • Trial primary completion date
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
|
BRCA2 mutation • BRCA1 mutation • PALB2 mutation
|
Lynparza (olaparib) • navitoclax (ABT 263)
4d
Unveiling the role of Pleckstrin-2 in tumor progression and immune modulation: insights from a comprehensive pan-cancer analysis with focus on lung cancer. (PubMed, Mol Biomed)
Compounds like Navitoclax were also identified as potential PLEK2 inhibitors. In conclusion, PLEK2 played a multifaceted role in cancer progression and immune response modulation. Targeting PLEK2 might suppress tumor growth and overcome immunotherapy resistance, offering a promising biomarker and therapeutic target to improve cancer treatment outcomes.
Journal • PD(L)-1 Biomarker • IO biomarker • Pan tumor
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CD8 (cluster of differentiation 8) • PLEK2 (Pleckstrin 2)
|
navitoclax (ABT 263)
7d
NCI-2013-02103: Testing the Addition of Navitoclax to the Combination of Dabrafenib and Trametinib in People Who Have BRAF Mutant Melanoma (clinicaltrials.gov)
P1/2, N=75, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
Trial completion date • Trial primary completion date • IO biomarker
|
PTEN (Phosphatase and tensin homolog) • BCL2 (B-cell CLL/lymphoma 2)
|
BRAF V600E • BRAF mutation • BRAF V600 • PTEN mutation • BRAF V600K
|
THXID® BRAF Kit • cobas® 4800 BRAF V600 Mutation Test
|
Mekinist (trametinib) • Tafinlar (dabrafenib) • navitoclax (ABT 263) • omipalisib (GSK2126458)
18d
Trial Treating Relapsed Acute Lymphoblastic Leukemia With Venetoclax and Navitoclax (clinicaltrials.gov)
P1/2, N=35, Active, not recruiting, St. Jude Children's Research Hospital | N=98 --> 35 | Trial completion date: Jul 2029 --> Mar 2025 | Trial primary completion date: Aug 2025 --> Jun 2024
Enrollment change • Trial completion date • Trial primary completion date
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Venclexta (venetoclax) • dasatinib • cytarabine • cyclophosphamide • etoposide IV • Blincyto (blinatumomab) • vincristine • navitoclax (ABT 263) • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • Asparlas (calaspargase pegol-mknl)
22d
Establishment of BCL-2 Inhibitors-Resistant B-cell Acute Lymphoblastic Leukemia Cell Lines and Study on Their Resistance Mechanisms (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
Drug-resistant B-ALL cell lines could be successfully established by exposing RS4;11 cell line to the ascending concentration of BCL-2 inhibitors, and the drug resistance mechanism may be related to the overexpression of EP300.
Preclinical • Journal • IO biomarker
|
EP300 (E1A binding protein p300)
|
BCL2 expression • EP300 overexpression
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Venclexta (venetoclax) • navitoclax (ABT 263)
27d
Dual ON/OFF-switch chimeric antigen receptor controlled by two clinically approved drugs. (PubMed, Proc Natl Acad Sci U S A)
We showed that inducible ON (iON)-CAR T cells respond to target tumors cells in the presence of venetoclax or the BH3 mimetic navitoclax in a dose-dependent manner, while there is no impact of the drugs on equivalent second generation-CAR T cells. Finally, by fusing a degron sequence to the endodomain of the iON-CAR S-chain we generated an all-in-one ON/OFF-switch CAR, the iONØ-CAR, down-regulated by lenalidomide within 4 to 6 for functionally inactive T cells (no IFNγ production) within 24 h. We propose that our remote-control CAR designs can reduce toxicity in the clinic. Moreover, the periodic rest of iON and iONØ-CAR T cells may alleviate exhaustion and hence augment persistence and long-term tumor control in patients.
Journal
|
IFNG (Interferon, gamma)
|
Venclexta (venetoclax) • lenalidomide • navitoclax (ABT 263)
1m
Comprehensive functional evaluation of head and neck squamous cell carcinoma with BH3-profiling demonstrates apoptotic competency and therapeutic efficacy of BH3-mimetics. (PubMed, Oral Oncol)
We assessed response to BH3 mimetics including ABT-263 (navitoclax), an inhibitor of Bcl-2/Bcl-xL/Bcl-w, and S63845, an inhibitor of Mcl-1, both as single agents and in combination. We found the combination to be highly synergistic in 2D culture and in 3D organoid models of HHNSCC. Given our findings that co-dependency on Bcl-xL and Mcl-1 is common, and co-inhibition of these molecules is synergistic for growth suppression in HNSCC cells, these results elucidate the therapeutic potential of BCL-xL and MCL-1 inhibition in HNSCC.
Journal
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BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • BCL2L2 (BCL2 Like 2)
|
MCL1 expression
|
navitoclax (ABT 263) • S63845
2ms
The Innate Immune System and TRAIL-BCL-XL Axis Mediate a Sex Bias in Lung Cancer and Confer a Therapeutic Vulnerability in Females. (PubMed, Cancer Res)
In both flank and orthotopic models, the BCL-XL inhibitor navitoclax (ABT-263) improved tumor growth control in female mice and required NK cells, macrophages, and the TRAIL signaling pathway. This research suggests that navitoclax and TRAIL pathway agonists could be used as a personalized therapy to improve outcomes in women with lung cancer.
Journal
|
BCL2L1 (BCL2-like 1) • NKG2D (killer cell lectin like receptor K1)
|
navitoclax (ABT 263)
2ms
Oncogenic Mutant p53 Sensitizes Non-Small Cell Lung Cancer Cells to Proteasome Inhibition via Oxidative Stress-Dependent Induction of Mitochondrial Apoptosis. (PubMed, Cancer Res Commun)
Validating BTZ's translational potential in Onc-p53 NSCLC cells, BTZ and the BH3-mimetic navitoclax were synergistically cytotoxic in Onc-p53 but not WT p53 cells in vitro, and BTZ effectively limited growth of Onc-p53 NSCLC xenografts when combined with navitoclax and carboplatin (a standard of care chemotherapeutic in NSCLC) in vivo. Our data therefore support further investigation of the therapeutic utility of PIs combined with BH3-mimetics and chemotherapy in Onc-p53 human NSCLC as a novel therapeutic strategy.
Journal
|
TP53 (Tumor protein P53) • CASP3 (Caspase 3) • PMAIP1 (Phorbol-12-Myristate-13-Acetate-Induced Protein 1) • ATF3 (Activating Transcription Factor 3)
|
TP53 mutation • TP53 wild-type
|
carboplatin • navitoclax (ABT 263)
2ms
Navitoclax, Venetoclax, and Decitabine for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia Previously Treated with Venetoclax (clinicaltrials.gov)
P1, N=17, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jan 2025 --> Dec 2025 | Trial primary completion date: Jul 2024 --> Dec 2024
Trial completion date • Trial primary completion date • Combination therapy
|
Venclexta (venetoclax) • decitabine • navitoclax (ABT 263)
2ms
ONC212, alone or in synergistic conjunction with Navitoclax (ABT-263), promotes cancer cell apoptosis via unconventional mitochondrial-independent caspase-3 activation. (PubMed, Cell Commun Signal)
Moreover, inhibition of caspase-9 activity unexpectedly augmented, rather than attenuated, caspase-3 activation and the subsequent cell death. Collectively, our research identifies ONC212 as an atypical mitochondrial-independent, yet Bcl-2/Bcl-xL-inhibitable, caspase-3-mediated apoptotic cell death inducer, highlighting its potential for combination therapies in tumors with defective mitochondrial apoptotic signaling.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • CASP3 (Caspase 3) • CASP8 (Caspase 8) • CASP9 (Caspase 9) • ANXA5 (Annexin A5)
|
BCL2 overexpression • BCL2 expression
|
navitoclax (ABT 263) • ONC212
2ms
IL-17A exacerbates corpus cavernosum fibrosis and neurogenic erectile dysfunction by inducing CSMC senescence via the mTORC2-ACACA pathway. (PubMed, BMC Med)
IL-17A assumes a pivotal role in denervated CCF by activating the mTORC2-ACACA signalling pathway, presenting itself as a potential therapeutic target for effectively overcoming CCF and erection rehabilitation in neurogenic ED.
Journal
|
BCL2 (B-cell CLL/lymphoma 2) • IL17A (Interleukin 17A) • ACACA (Acetyl-CoA Carboxylase Alpha)
|
navitoclax (ABT 263)
3ms
HSF1 is a prognostic determinant and therapeutic target in intrahepatic cholangiocarcinoma. (PubMed, J Exp Clin Cancer Res)
The present data underscore the critical pathogenetic, prognostic, and therapeutic role of HSF1 in cholangiocarcinogenesis.
Journal
|
BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • BCL2L2 (BCL2 Like 2) • NICD (NOTCH1 intracellular domain) • HSF1 (Heat Shock Transcription Factor 1)
|
navitoclax (ABT 263)
3ms
MERTK Is a Potential Therapeutic Target in Ewing Sarcoma. (PubMed, Cancers (Basel))
Combined treatment with MRX-2843 and BCL-2 inhibitors venetoclax or navitoclax provided enhanced therapeutic activity compared to single agents. These data highlight MERTK as a promising therapeutic target in EWS and provide rationale for the development of MRX-2843 for the treatment of EWS, especially in combination with BCL-2 inhibitors.
Journal
|
MERTK (MER Proto-Oncogene, Tyrosine Kinase)
|
Venclexta (venetoclax) • navitoclax (ABT 263) • MRX2843
3ms
Therapeutic Senolysis of Axitinib-Induced Senescent Human Lung Cancer Cells. (PubMed, Cancers (Basel))
These cells were cultured with axitinib or a multi-target TKI lenvatinib. Axitinib-induced senescent lung adenocarcinoma A549 cells were drastically lysed by ABT-263. In A549-xenografted mice, combination therapy with axitinib and ABT-263 significantly suppressed tumor growth with the induction of apoptotic cancer cells.
Journal
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CXCL8 (Chemokine (C-X-C motif) ligand 8) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
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Lenvima (lenvatinib) • Inlyta (axitinib) • navitoclax (ABT 263)
3ms
Chromosome instability functions as a potential therapeutic reference by enhancing chemosensitivity to BCL-XL inhibitors in colorectal carcinoma. (PubMed, Acta Pharmacol Sin)
By using machine learning methods, we screened out two BCL-XL inhibitors Navitoclax and WEHI-539 as CIN-sensitive reagents in CRC...In addition, to ease the evaluation of CIN levels in clinic, we developed a three-gene signature as a CIN surrogate to predict prognosis, chemotherapeutic and immune responses in CRC samples. Our results demonstrate the potential value of CIN as a therapeutic target in CRC treatment and the importance of BCL-XL in regulating survival of high-CIN CRC cells, therefore representing a valuable attempt to translate a common trait of heterogeneous tumor cells into an effective therapeutic target.
Journal
|
BCL2L1 (BCL2-like 1)
|
navitoclax (ABT 263)
3ms
Tryptanthrin targets GSTP1 to induce senescence and increases the susceptibility to apoptosis by senolytics in liver cancer cells. (PubMed, Redox Biol)
Importantly, TRYP exposed the vulnerability of tumor cells and sensitized senescent cells to apoptosis induced by senolytic agent ABT263, a Bcl2 inhibitor. Taken together, our findings reveal that TRYP induces cellular senescence via GSTP1/ROS/DDR/NF-κB/SASP axis, providing a novel potential application in synergizing with senolytic therapy in liver cancer.
Journal
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GSTP1 (Glutathione S-transferase pi 1)
|
navitoclax (ABT 263)
3ms
Venetoclax-Navitoclax With Cladribine-based Salvage Therapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov)
P1, N=0, Withdrawn, Medical College of Wisconsin | N=36 --> 0 | Initiation date: May 2024 --> Aug 2024 | Not yet recruiting --> Withdrawn
Enrollment change • Trial initiation date • Trial withdrawal
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Venclexta (venetoclax) • cytarabine • navitoclax (ABT 263) • mitoxantrone • Neupogen (filgrastim)
3ms
Genetically Risk-Stratified Venetoclax, Ibrutinib, Rituximab (± Navitoclax) in Relapsed/Refractory Mantle Cell Lymphoma (clinicaltrials.gov)
P2, N=40, Active, not recruiting, Peter MacCallum Cancer Centre, Australia | Recruiting --> Active, not recruiting
Enrollment closed
|
BCL2 (B-cell CLL/lymphoma 2) • BCL2L2 (BCL2 Like 2) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
|
Venclexta (venetoclax) • Imbruvica (ibrutinib) • Rituxan (rituximab) • navitoclax (ABT 263)
4ms
Biomarkers related to m6A and succinic acid metabolism in papillary thyroid carcinoma. (PubMed, BMC Med Genomics)
Overall, we described 5 biomarkers associated with adverse prognosis of PTC, including ADK, TNFRSF10B, CYP7B1, FGFR2, and CPQ. All these biomarkers were involved in succinate metabolism and m6A modification of RNA. This set of biomarkers should be explored further for their diagnostic value in PTC. Investigations into the mechanistic role of alteration of succinate metabolism and m6A modification of RNA pathways in the pathophysiology of PTC are warranted.
Journal
|
FGFR2 (Fibroblast growth factor receptor 2) • TNFRSF10B (TNF Receptor Superfamily Member 10b)
|
navitoclax (ABT 263)
4ms
Combination Navitoclax, Venetoclax and Decitabine for Advanced Myeloid Neoplasms (clinicaltrials.gov)
P1, N=16, Active, not recruiting, Jacqueline Garcia, MD | Recruiting --> Active, not recruiting | N=36 --> 16
Enrollment closed • Enrollment change • Metastases
|
Venclexta (venetoclax) • decitabine • navitoclax (ABT 263)
5ms
Synergy of retinoic acid and BH3 mimetics in MYC(N)-driven embryonal nervous system tumours. (PubMed, Br J Cancer)
RA treatment primes MBG3 and NB cells for apoptosis, triggered by navitoclax cotreatment.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1)
|
navitoclax (ABT 263)
5ms
Trial completion date • Combination therapy
|
Jakafi (ruxolitinib) • navitoclax (ABT 263)
5ms
Trial completion date • Combination therapy
|
Jakafi (ruxolitinib) • navitoclax (ABT 263)
5ms
Androgen deprivation-induced senescence confers sensitivity to a senolytic strategy in prostate cancer. (PubMed, Biochem Pharmacol)
Moreover, the Bcl-XL/Bcl-2 inhibitor, ABT-263 (navitoclax), an established senolytic agent, promoted apoptosis of senescent PCa cells, suppressing proliferative recovery and subsequent tumor cell outgrowth...However, as is often the case in studies combining the promotion of senescence with a senolytic (the "one-two" punch approach), the suppression of tumor growth by the inclusion of the senolytic agent was transient, allowing for tumor regrowth once the drug treatment was terminated. Nevertheless, the results of this work suggest that the "one-two" punch senolytic strategy in PCa may effectively interfere with, diminish, or delay the development of the lethal castration-resistant phenotype.
Journal
|
BCL2L1 (BCL2-like 1)
|
navitoclax (ABT 263)
5ms
HEM-iSMART A: HEM-iSMART-A: Decitabine / Venetoclax and Navitoclax in Pediatric Patients With Relapsed or Refractory Hematological Malignancies (clinicaltrials.gov)
P1/2, N=0, Withdrawn, Princess Maxima Center for Pediatric Oncology | N=26 --> 0 | Not yet recruiting --> Withdrawn
Enrollment change • Trial withdrawal
|
Venclexta (venetoclax) • cytarabine • decitabine • navitoclax (ABT 263)
5ms
Trial completion date • Combination therapy
|
JAK2 (Janus kinase 2)
|
Jakafi (ruxolitinib) • navitoclax (ABT 263)
5ms
Coupling Kinesin Spindle Protein and Aurora B Inhibition with Apoptosis Induction Enhances Oral Cancer Cell Killing. (PubMed, Cancers (Basel))
Here, we investigated the impact of inhibiting anti-apoptotic signals with the BH3-mimetic Navitoclax in oral cancer cells treated with the selective KSP inhibitor, Ispinesib, or AurB inhibitor, Barasertib, aiming to potentiate cell death. A mechanistic analysis underlying this synergistic activity, undertaken by live-cell imaging, is presented. Our data underscore the importance of combining BH3-mimetics with antimitotics in clinical trials to maximize their effectiveness.
Journal
|
AURKB (Aurora Kinase B)
|
navitoclax (ABT 263) • ispinesib (SB-715992) • barasertib (AZD1152)
5ms
A Study Evaluating Safety and Tolerability, and Pharmacokinetics of Navitoclax Monotherapy and in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasm (clinicaltrials.gov)
P1, N=85, Active, not recruiting, AbbVie | Trial completion date: Sep 2024 --> Jan 2025 | Trial primary completion date: Sep 2024 --> Jan 2025
Trial completion date • Trial primary completion date • Combination therapy
|
Jakafi (ruxolitinib) • navitoclax (ABT 263)
5ms
Safety and Tolerability Study of Oral ABBV-744 Tablet Alone or in Combination With Oral Ruxolitinib Tablet or Oral Navitoclax Tablet in Adult Participants With Myelofibrosis (clinicaltrials.gov)
P1, N=21, Active, not recruiting, AbbVie | Phase classification: P1b --> P1 | Trial completion date: Jul 2024 --> Nov 2024 | Trial primary completion date: Jul 2024 --> Nov 2024
Phase classification • Trial completion date • Trial primary completion date • Combination therapy
|
Jakafi (ruxolitinib) • navitoclax (ABT 263) • ABBV-744
5ms
Integrated analysis of ferroptosis and stemness based on single-cell and bulk RNA-sequencing data provide insights into the prognosis and treatment of esophageal carcinoma. (PubMed, Gene)
This study constructed a novel ferroptosis-related stemness signature, identified two marker genes for ESCA, and provided valuable insights for developing more effective therapeutic targets targeting ESCA CSCs in the future.
Journal • PARP Biomarker
|
SLC2A1 (Solute Carrier Family 2 Member 1) • STMN1 (Stathmin 1)
|
Talzenna (talazoparib) • Inlyta (axitinib) • navitoclax (ABT 263) • foretinib (GSK1363089)
5ms
Effects of triggers of senescence and senolysis in murine pancreatic cancer cells. (PubMed, Hepatobiliary Pancreat Dis Int)
In vitro and in vivo, the combination of senescence triggers with Nav inhibited tumor cell growth more effectively than the triggers alone. Our data also provide some evidence for senolytic effects of Nav in vitro.
Preclinical • Journal • IO biomarker
|
CDKN1A (Cyclin-dependent kinase inhibitor 1A)
|
etoposide IV • navitoclax (ABT 263)
5ms
Safety Study of ABT-263 in Combination With Rituximab in Lymphoid Cancers (clinicaltrials.gov)
P1, N=29, Active, not recruiting, AbbVie | Trial completion date: May 2024 --> Jan 2025 | Trial primary completion date: May 2024 --> Jan 2025
Trial completion date • Trial primary completion date • Combination therapy
|
CD20 (Membrane Spanning 4-Domains A1)
|
Rituxan (rituximab) • navitoclax (ABT 263)
6ms
Identification of a Macrophage marker gene signature to evaluate immune infiltration and therapeutic response in hepatocellular carcinoma. (PubMed, Heliyon)
Moreover, a low-Macrosig score indicates increased sensitivity to AZD.2281, A.443654, ABT.263, ABT.888, AG.014699 and ATRA, while a high Macrosig score indicates increased sensitivity to AZD6482, AKT inhibitor VIII, AS601245, AZ628, AZD.0530 and AZD6244. A novel scoring system was constructed to guide more effective prognostic evaluation and tailoring therapeutic regimens for HCC patients.
Journal • Gene Signature • PD(L)-1 Biomarker • IO biomarker
|
PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2)
|
Lynparza (olaparib) • Koselugo (selumetinib) • Rubraca (rucaparib) • veliparib (ABT-888) • navitoclax (ABT 263) • AZ 628 • saracatinib (AZD0530) • AZD6482 • A 443654
6ms
Navitoclax, Venetoclax, and Decitabine for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia Previously Treated With Venetoclax (clinicaltrials.gov)
P1, N=17, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting | N=36 --> 17
Enrollment closed • Enrollment change • Combination therapy
|
Venclexta (venetoclax) • decitabine • navitoclax (ABT 263)
6ms
Molecular mechanisms of extracellular-ATP-mediated colorectal cancer progression: Implication of purinergic receptors-mediated nucleocytoplasmic shuttling of HuR. (PubMed, Purinergic Signal)
In addition, e-ATP-induced Caco-2 cell proliferation as well as cell survival were highly reduced in the presence of either PPADS or DHTS or selective CDK-2 inhibitor (Roscovitine) or selective Bcl-2 inhibitor (ABT-263). Furthermore, it was found that MMP-9 is critical for Caco-2 cells migration induced by e-ATP as demonstrated by a clear reduction in cells migration in the presence of a selective MMP-9 inhibitor (Marimastat). Collectively, these data demonstrate that ATP through P2R activation can induce HuR nucleocytoplasmic shuttling that could be translated into an increase in cancer-related genes expression and subsequent, cell proliferation and progression.
Journal • IO biomarker
|
HIF1A (Hypoxia inducible factor 1, alpha subunit) • CCNA2 (Cyclin A2) • TGFB1 (Transforming Growth Factor Beta 1) • MMP9 (Matrix metallopeptidase 9)
|
navitoclax (ABT 263) • seliciclib (CYC202)
6ms
Mitochondrial bioenergetics as a cell fate rheostat for responsive to Bcl-2 drugs: New cues for cancer chemotherapy. (PubMed, Cancer Lett)
Conversely, mutations in isocitrate dehydrogenase 1 and 2, catalyzing R-2-hydroxyglutarate production, promote sensitivity to Venetoclax...Ongoing clinical trials are evaluating BH3-mimetics in combination with standard chemotherapeutics. In this article, we discuss the role of mitochondrial bioenergetics in response to BH3-mimetics and explore potential therapeutic opportunities through metabolism-targeting strategies.
Review • Journal • IO biomarker
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • BCL2 (B-cell CLL/lymphoma 2)
|
Venclexta (venetoclax) • navitoclax (ABT 263)
6ms
Enrollment closed
|
JAK2 (Janus kinase 2)
|
Jakafi (ruxolitinib) • navitoclax (ABT 263)
6ms
Navitoclax and Sorafenib Tosylate in Treating Patients With Relapsed or Refractory Solid Tumors (clinicaltrials.gov)
P1, N=29, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2024 --> May 2025
Trial completion date
|
MCL1 (Myeloid cell leukemia 1) • AFP (Alpha-fetoprotein) • CASP3 (Caspase 3)
|
MCL1 expression
|
sorafenib • navitoclax (ABT 263)
6ms
CD4+CD57+ senescent T cells as promoters of systemic lupus erythematosus pathogenesis and the therapeutic potential of senolytic BCL-2 inhibitor. (PubMed, Eur J Immunol)
Further, treatment with ABT-263 (a senolytic BCL-2 inhibitor) in MRL/lpr mice resulted in decreased: (1) frequency of CD4+CD44hiCD62L-PD-1+CD153+ senescent CD4+ T cells; (2) frequency of CD19+CD11c+T-bet+ age-related B cells; (3) level of serum antinuclear antibody; (4) proteinuria; (5) frequency of Tfh cells; and (6) renal histopathological abnormalities. Collectively, these results indicated a dominant role for CD4+CD57+ senescent CD4+ T cells in the pathogenesis of SLE and senolytic BCL-2 inhibitor ABT-263 may be the potential treatment in ameliorating lupus phenotypes.
Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-1 (Programmed cell death 1) • CD4 (CD4 Molecule) • IL15 (Interleukin 15) • ITGAX (Integrin Subunit Alpha X) • B3GAT1 (Beta-1,3-Glucuronyltransferase 1)
|
BCL2 expression
|
navitoclax (ABT 263)
6ms
Evaluation of BH3 mimetics as a combination therapy with irradiation in head and neck squamous cell carcinoma. (PubMed, Biomed Pharmacother)
Our findings encourage the further preclinical investigation of BH3 mimetics, particularly A-1331852, as a single agent or combined with irradiation as a treatment for HNSCC.
Journal • Combination therapy
|
BCL2 (B-cell CLL/lymphoma 2)
|
navitoclax (ABT 263) • A-1331852
6ms
ALK inhibitors suppress HCC and synergize with anti-PD-1 therapy and ABT-263 in preclinical models. (PubMed, iScience)
Hepatocellular carcinoma (HCC) currently lacks effective therapies, leaving a critical need for new treatment options. Additional studies identified that the apoptosis-inducing effect of lorlatinib was mediated via GGN and NRG4. These findings establish ALK inhibitors as promising HCC treatments, either alone or in combination with immunotherapies or senolytic agents.
Preclinical • Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK amplification
|
Lorbrena (lorlatinib) • navitoclax (ABT 263)