^
Contact us  to learn more about
our Premium Content:  News alerts, weekly reports and conference planners
BIOMARKER:

MCL1 expression

i
Other names: MCL1, MCL1 Apoptosis Regulator BCL2 Family Member, Induced Myeloid Leukemia Cell Differentiation Protein Mcl-1, Myeloid Cell Leukemia Sequence 1 (BCL2-Related), MCL1 BCL2 Family Apoptosis Regulator, Bcl-2-Related Protein EAT/Mcl1, Myeloid Cell Leukemia 1, Bcl-2-Like Protein 3, Bcl2-L-3, Mcl1/EAT, BCL2L3, BCL2 Family Apoptosis Regulator, Myeloid Cell Leukemia ES, MCL1-ES, MCL1L, MCL1S, Mcl-1, EAT, TM
Entrez ID:
Related biomarkers:
4d
BCL-2 inhibition in haematological malignancies: Clinical application and complications. (PubMed, Blood Rev)
There are also clinical problems with BCL-2 family inhibition, including drug resistance, disease relapse, tumour lysis syndrome, and clinically relevant cytopenias. Here, we provide a balanced view on both the clinical benefits of BCL-2 inhibition as well as the associated challenges.
Review • Journal • IO biomarker
|
MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1)
|
MCL1 expression
|
Venclexta (venetoclax)
5d
In silico design of potential Mcl-1 peptide-based inhibitors. (PubMed, J Mol Model)
Finally, molecular dynamics simulations run for 100 ns were done using the GROMACS, version 5.0.7, with the CHARMM36 force field. MM-PBSA was used to assess binding affinity specificity in targeting Mcl-1 and Bcl-xL (B-cell lymphoma extra-large).
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1)
|
MCL1 overexpression • MCL1 expression
11d
PHA-665752's Antigrowth and Proapoptotic Effects on HSC-3 Human Oral Cancer Cells. (PubMed, Int J Mol Sci)
Importantly, genetic ablation of c-Met caused the reduced growth of HSC-3 cells and decreased Src phosphorylation and HIF-1α expression. Together, these results demonstrate that c-Met is highly activated in HSC-3 human oral cancer cells, and PHA exhibits strong antigrowth, proapoptotic, and antiangiogenic effects on these cells, which are mediated through regulation of the phosphorylation and expression of multiple targets, including c-Met, Src, PKB, mTOR, Mcl-1, and HIF-1α.
Journal
|
mTOR (Mechanistic target of rapamycin kinase) • HIF1A (Hypoxia inducible factor 1, alpha subunit)
|
MET expression • MCL1 expression • HIF1A expression
|
PHA665752
12d
Anlotinib Inhibits Cisplatin Resistance in Non-Small-Cell Lung Cancer Cells by Inhibiting MCL-1 Expression via MET/STAT3/Akt Pathway. (PubMed, Can Respir J)
Anlotinib is an effective targeted therapy for advanced non-small-cell lung cancer (NSCLC) and has been found to mediate chemoresistance in many cancers. Furthermore, MET overexpression reversed the inhibitory effect of anlotinib on the DDP resistance of NSCLC cells, and this effect could be eliminated by MCL-1 knockdown or ACT001 (an inhibitor for STAT3/Akt pathway). Our results confirmed that anlotinib inhibited DDP resistance in NSCLC cells, which might decrease MCL-1 expression via mediating the MET/STAT3/Akt pathway.
Journal
|
MCL1 (Myeloid cell leukemia 1)
|
MET overexpression • MET expression • MCL1 expression • STAT3 expression
|
cisplatin • Focus V (anlotinib) • dimethylamino micheliolide (ACT001)
15d
MCL1 inhibition targets Myeloid Derived Suppressors Cells, promotes antitumor immunity and enhances the efficacy of immune checkpoint blockade. (PubMed, Cell Death Dis)
In this study, we show that the MCL1 inhibitor S64315 reduces melanoma tumor growth in an immune cell-dependent manner in mice...Together, this proof-of-concept study demonstrates the potential of combining an MCL1 inhibitor with anti-PD-1 in the treatment of melanoma. It justifies the further development of next generation MCL1 inhibitors to improve efficacy of ICIs in treating malignant melanoma.
Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker • Checkpoint block
|
BCL2 (B-cell CLL/lymphoma 2) • CD8 (cluster of differentiation 8)
|
MCL1 expression
|
MIK665
22d
BCL-XL inhibitors enhance the apoptotic efficacy of BRAF inhibitors in BRAFV600E colorectal cancer. (PubMed, Cell Death Dis)
While the BRAFV600E inhibitor encorafenib in combination with the EGFR inhibitor cetuximab (Enc+Cet) was recently approved for this indication, overall survival is only increased by 3.6 months and objective responses are observed in only 20% of patients. Combining encorafenib with DT2216 significantly increased apoptosis induction in vitro, while combining encorafenib with AZD0466 was well tolerated in mice and further reduced growth of BRAFV600E CRC xenografts compared to either agent alone. Collectively, these findings demonstrate that combined BRAF and BCL-XL inhibition significantly enhances apoptosis in pre-clinical models of BRAFV600E CRC and is a combination regimen worthy of clinical investigation to improve outcomes for these patients.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1) • BCL2L11 (BCL2 Like 11)
|
BRAF V600E • BRAF V600 • MCL1 expression • BCL2L11 deletion
|
Erbitux (cetuximab) • Braftovi (encorafenib) • DT2216 • AZD0466
23d
Mechanisms of resistance to venetoclax in hematologic malignancies. (PubMed, Adv Clin Exp Med)
Moreover, alterations in cell metabolism and signaling pathways like MAPK or ERK activation have also been reported, suggesting the resistance to venetoclax is highly complex and involves multiple pathways. This review aimed to describe the mechanisms of resistance to venetoclax in AML, CLL, multiple myeloma, and other hematologic malignancies, as well as to propose a perspective to circumvent it.
Review • Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2)
|
MCL1 expression
|
Venclexta (venetoclax)
25d
Effect of venetoclax plus chemotherapy on treatment-naive acute myeloid leukemia patients with moderate to poor cytogenetic profiles and the combination's influence on the expression of proteins of the anti-apoptoic family (PubMed, Zhonghua Zhong Liu Za Zhi)
The chemotherapy cohort received 2 cycles of induction chemotherapy (idarbicin or daunorubicin plus cytarabine), followed by 6 cycles of consolidation chemotherapy (cytarabine), while the treatment for the VEN + chemotherapy cohort consisted of the same chemotherapy as above plus oral VEN. VEN combined with intensive chemotherapy have yielded high ORR and survival advantages for de novo AML patients with poor cytogenetics profiles. The high-expression of MCL-1 may drive resistance to VEN.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1)
|
BCL2 expression • MCL1 expression
|
Venclexta (venetoclax) • cytarabine • daunorubicin
27d
Characterization of BCL-XL, MCL-1, and BAX Protein Expression in Response to Neoadjuvant Chemotherapy in Breast Cancer. (PubMed, Appl Immunohistochem Mol Morphol)
There was no statistically significant association between the expression of these markers and stage, grade, and hormone receptor profiling (luminal status). Collectively, our data indicate that the expression of apoptosis regulatory proteins changes following exposure to NAC in breast cancer tissue, developing a partial pathologic response.
Journal
|
MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1) • BAX (BCL2-associated X protein)
|
MCL1 expression • BAX expression
1m
Tumor Treating Fields (TTFields) combined with the drug repurposing approach CUSP9v3 induce metabolic reprogramming and synergistic anti-glioblastoma activity in vitro. (PubMed, Br J Cancer)
TTFields strongly enhance the CUSP9v3-mediated anti-glioblastoma activity. TTFields are currently widely used for the treatment of glioblastoma patients and CUSP9v3 was shown to have a favorable safety profile in a phase Ib/IIa trial (NCT02770378) which facilitates transition of this multimodal approach to the clinical setting.
Preclinical • Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1) • CASP3 (Caspase 3)
|
BCL2 expression • MCL1 expression
|
temozolomide
1m
The Role of miR-29a and miR-143 on the Anti-apoptotic MCL-1/cIAP-2 Genes Expression in EGFR Mutated Non-small Cell Lung Carcinoma Patients. (PubMed, Biochem Genet)
Dual-luciferase reporter experiments confirmed that miR-29a and miR-143 target MCL-1 and cIAP-2 mRNAs, respectively. Our results suggest that upregulation of EGFR signaling in lung cancer cells may increase anti-apoptotic MCL-1 and cIAP-2 gene expression, possibly through downregulation of miR-29a-3p and miR-143-3p.
Journal
|
EGFR (Epidermal growth factor receptor) • MCL1 (Myeloid cell leukemia 1) • MIR143 (MicroRNA 143) • MIR29A (MicroRNA 29a)
|
EGFR mutation • EGFR expression • EGFR wild-type • MCL1 expression
2ms
GZ17-6.02 interacts with bexarotene to kill mycosis fungoides cells. (PubMed, Oncotarget)
Inhibition of autophagy and knock down of death-mediators downstream of the mitochondrion, AIF and caspase 3, almost abolished tumor cell killing. Hence in MF cells, GZ17-6.02 is a multi-factorial killer, utilizing ER stress, macroautophagy, death receptor signaling and directly causing mitochondrial dysfunction.
Journal
|
MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1) • CASP3 (Caspase 3) • FAS (Fas cell surface death receptor) • AMPK (Protein Kinase AMP-Activated Catalytic Subunit Alpha 1) • BECN1 (Beclin 1)
|
MCL1 expression
|
Zolinza (vorinostat) • GZ17-6.02 • Targretin oral (bexarotene oral)
2ms
Inhibitory effect of miR342 on the progression of triple-negative breast cancer cells in vitro and in the mice model. (PubMed, Bioimpacts)
Moreover, decreased expression of Bcl2l1, Mcl1, and ID4, as miR342 target genes, was observed, accompanied by reduced expression of VEGF and Bcl2/Bax ratio at the protein level. To conclude, our data support the idea that miR342 might be a potential therapeutic target for the treatment of triple-negative breast cancer (TNBC).
Preclinical • Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • BAX (BCL2-associated X protein) • MIR342 (MicroRNA 342)
|
BCL2 expression • MCL1 expression • BAX expression • VEGFA expression • BCL2/BAX ratio elevation
2ms
Tomivosertib in Relapsed or Refractory Acute Myeloid Leukemia (AML) (clinicaltrials.gov)
P1, N=15, Recruiting, Northwestern University | Active, not recruiting --> Recruiting
Enrollment open
|
MCL1 (Myeloid cell leukemia 1)
|
MCL1 expression
|
tomivosertib (eFT508)
2ms
Notoginsenoside R1 attenuates bupivacaine induced neurotoxicity by activating Jak1/Stat3/Mcl1 pathway. (PubMed, Toxicology)
In addition, NG-R1 can also promote Jak1 phosphorylation and docking analysis provide a predicted model for interaction between NG-R1 and phosphorylated Jak1. Taken together, our results demonstrated that NG-R1 can attenuate bupivacaine induced neurotoxicity by activating Jak1/Stat3/Mcl1 pathway.
Journal
|
MCL1 (Myeloid cell leukemia 1) • JAK1 (Janus Kinase 1)
|
MCL1 expression
2ms
The Effects of ABT-199 and Dihydroartemisinin Combination on Cell Growth and Apoptosis in Human U937 and KG-1 Cancer Cells. (PubMed, Asian Pac J Cancer Prev)
In conclusion, dihydroartemisinin not only triggers the intrinsic pathway of apoptosis, but also can increase the sensitivity of the AML cells to ABT-199 via suppression of Mcl-1 expression.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • CASP3 (Caspase 3)
|
BCL2 expression • MCL1 expression • BAX expression
|
Venclexta (venetoclax)
2ms
Dihydroartemisinin Enhances the Therapeutic Efficacy of BH3 Mimetic Inhibitor in Acute Lymphoblastic Leukemia Cells via Inhibition of Mcl-1. (PubMed, Asian Pac J Cancer Prev)
In conclusion, dihydroartemisinin demonstrates anti-tumor activities in human ALL cells via inhibition of cell survival and growth. Dihydroartemisinin augments the apoptotic effect of ABT-737 by inhibiting the expression of Mcl-1.
Journal • IO biomarker
|
CASP3 (Caspase 3) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
|
BCL2 expression • MCL1 expression • BAX expression
|
ABT-737
2ms
Pim kinase inhibitors increase gilteritinib cytotoxicity in FLT3-ITD acute myeloid leukemia through GSK-3β activation and c-Myc and Mcl-1 proteasomal degradation. (PubMed, Cancer Res Commun)
Cytotoxicity, apoptosis and protein expression and turnover were measured in FLT3-ITD-expressing cell lines and AML patient blasts treated with the FLT3 inhibitor gilteritinib and/or the Pim inhibitors AZD1208 or TP-3654. The data are consistent with c-Myc T58 and Mcl-1 S159 phosphorylation by activated GSK-3β as the mechanism of action of gilteritinib and Pim inhibitor combination treatment, further supporting GSK-3β activation as a therapeutic strategy in FLT3-ITD AML.  .
Journal
|
FLT3 (Fms-related tyrosine kinase 3) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MCL1 (Myeloid cell leukemia 1) • PIM1 (Pim-1 Proto-Oncogene)
|
MYC expression • MCL1 expression • FLT3-ITD expression • MCL1 S159A
|
Xospata (gilteritinib) • AZD1208 • TP-3654
2ms
Pan-EGFR Inhibitor Dacomitinib Resensitizes Paclitaxel and Induces Apoptosis via Elevating Intracellular ROS Levels in Ovarian Cancer SKOV3-TR Cells. (PubMed, Molecules)
Additionally, we confirmed that dacomitinib inhibits chemoresistance in paclitaxel-resistant ovarian cancer HeyA8-MDR cells. Collectively, our research indicated that dacomitinib effectively resensitized paclitaxel in SKOV3-TR cells by inhibiting EGFR signaling and elevating intracellular ROS levels.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • MCL1 (Myeloid cell leukemia 1) • STAT3 (Signal Transducer And Activator Of Transcription 3)
|
MCL1 expression
|
paclitaxel • Vizimpro (dacomitinib)
3ms
Engineering a CRISPRoff Platform to Modulate Expression of Myeloid Cell Leukemia (MCL-1) in Committed Oligodendrocyte Neural Precursor Cells. (PubMed, Bio Protoc)
We modified CRISPRoff and sgRNA Sleeping Beauty transposon vectors that depend on tetracycline-controlled transcriptional activation to silence the expression of embryonic lethal genes at different stages of differentiation in a stable manner...• Experiments performed in vitro for generation of inducible CRISPRoff pluripotent stem cell line amenable to oligodendrocyte differentiation. • Strategy to downregulate an essential gene at different stages of oligodendrocyte development.
Journal
|
MCL1 (Myeloid cell leukemia 1)
|
MCL1 expression
3ms
PRKCSH contributes to TNFSF resistance by extending IGF1R half-life and activation in lung cancer. (PubMed, Exp Mol Med)
PRKCSH deficiency augmented the antitumor effects of natural killer (NK) cells, representative TNFSF effector cells, in a tumor xenograft IL-2Rg-deficient NOD/SCID (NIG) mouse model. Our data suggest that PRKCSH plays a critical role in TNFSF resistance and may be a potential target to improve the efficacy of NK cell-based cancer therapy.
Journal
|
MCL1 (Myeloid cell leukemia 1) • TNFA (Tumor Necrosis Factor-Alpha) • CASP8 (Caspase 8) • CASP9 (Caspase 9)
|
MCL1 expression
3ms
BCL-XL regulates the timing of mitotic apoptosis independently of BCL2 and MCL1 compensation. (PubMed, Cell Death Dis)
Nevertheless, even in a MCL1-deficient background, depletion of BCL-XL accelerated mitotic apoptosis. These findings underscore the pivotal involvement of BCL-XL in controlling timely apoptosis during mitotic arrest, despite adaptive changes in the expression of other BCL2-like proteins.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1)
|
BCL2 expression • MCL1 expression
3ms
Phosphoproteomic Characterization and Kinase Signature Predict Response to Venetoclax Plus 3+7 Chemotherapy in Acute Myeloid Leukemia. (PubMed, Adv Sci (Weinh))
Venetoclax with 3+7 daunorubicin and cytarabine (DAV regimen) in young adult de novo AML patients is evaluated. Notably, AKT1 inhibition augments the antileukemic efficacy of DAV treatment in AML. Overall, this phosphoproteomic study identifies the role of AURKB as a predictive biomarker for DA, but not DAV, resistance and proposes a promising strategy to counteract therapy resistance in AML.
Journal
|
AKT1 (V-akt murine thymoma viral oncogene homolog 1) • MCL1 (Myeloid cell leukemia 1) • AURKB (Aurora Kinase B)
|
MCL1 expression
|
Venclexta (venetoclax) • cytarabine • daunorubicin
3ms
Zotiraciclib (TG02) for newly diagnosed glioblastoma in the elderly or for recurrent glioblastoma: The EORTC 1608 STEAM trial. (PubMed, Eur J Cancer)
TG02 exhibits overlapping toxicity with alkylating agents and low single agent clinical activity in recurrent glioblastoma. The role of CDK-9 and its down-stream effectors as prognostic factors and therapeutic targets in glioblastoma warrants further study.
Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MCL1 (Myeloid cell leukemia 1) • CDK9 (Cyclin Dependent Kinase 9)
|
MYC overexpression • MYC expression • MCL1 expression • IDH wild-type
|
temozolomide • zotiraciclib (TG02)
3ms
The Expression of miR-34c-5p Induces G0/G1 Cell Cycle Arrest and Apoptosis in SW480 Colon Cancer Cell. (PubMed, Iran J Pharm Res)
However, no remarkable difference was seen in the expression of MCL1, BCL2, and CASPASE 3 genes. Our conclusion is that overexpression of miR-34c-5p could be considered a promising approach for colorectal cancer treatment.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1) • CASP3 (Caspase 3) • MIR34A (MicroRNA 34a-5p) • CASP9 (Caspase 9) • CASP7 (Caspase 7)
|
BCL2 expression • MCL1 expression
3ms
Distinct roles of hematopoietic cytokines in the regulation of leukemia stem cells in murine MLL-AF9 leukemia. (PubMed, Stem Cell Reports)
Functional study demonstrated that, compared to AML cells cultured in IL-3 and IL-6 medium, AML cells in SCF- or Flt3L-only culture are highly clonogenic in in vitro culture and are highly leukemogenic in vivo. Our study suggests that co-inhibition of both STAT5-MCL1 and STAT3/NF-κB-BCL2 signaling might represent an improved treatment strategy against AML, specifically AML cases with a monocytic phenotype and/or FLT3 mutations.
Preclinical • Journal • IO biomarker
|
FLT3 (Fms-related tyrosine kinase 3) • BCL2 (B-cell CLL/lymphoma 2) • IL6 (Interleukin 6) • STAT5A (Signal Transducer And Activator Of Transcription 5A)
|
FLT3 mutation • BCL2 expression • MCL1 expression
4ms
A p53 score derived from TP53 CRISPR/Cas9 HMCLs predicts survival and reveals major role of BAX in BH3 mimetics response. (PubMed, Blood)
At the functional level, we showed that among the 13 genes, p53-regulated BAX expression correlated to, and directly impacted, the MCL1 BH3 mimetic S63845 sensitivity of myeloma cells by decreasing MCL1-BAX complexes...Nevertheless, scRNAseq analysis showed that myeloma cells surviving to the combination had lower p53 score, showing that myeloma cells with higher p53 score were more sensitive to BH3 mimetics. Taken together, we established a functional p53 score that identifies myeloma cells with biallelic TP53 invalidation, demonstrated that p53-regulated BAX is critical for optimal cell response to BH3 mimetics, and showed that MCL1 and BCL2 BH3 mimetics combination may be of interest for patients with biallelic TP53 invalidation, for whom there is still an unmet medical need.
Journal • IO biomarker
|
TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1) • BAX (BCL2-associated X protein)
|
Chr t(4;14) • MCL1 expression • TP53 expression • BAX expression
|
S63845
4ms
Bio-orthogonally Activatable Fluorescent Probe for Specific Imaging of Myeloid Cell Leukemia 1 Protein. (PubMed, Anal Chem)
Also, the level changes of Mcl-1 upon drug challenge were demonstrated. This work provides a robust fluorescence strategy for Mcl-1 in situ imaging, and the results would further facilitate the comprehensive revelation of the Mcl-1 biological effect.
Journal
|
MCL1 (Myeloid cell leukemia 1)
|
MCL1 expression
4ms
FBXW7 affects autophagy through MCL1 in oral squamous cell carcinoma. (PubMed, Oral Dis)
Our results suggest that FBXW7 affects autophagy through MCL1 in OSCC.
Journal
|
MCL1 (Myeloid cell leukemia 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATG7 (Autophagy Related 7) • BECN1 (Beclin 1)
|
MCL1 overexpression • MCL1 expression • FBXW7 overexpression
4ms
Dinaciclib synergizes with BH3 mimetics targeting BCL-2 and BCL-X in multiple myeloma cell lines partially-dependent on MCL-1 and in plasma cells from patients. (PubMed, Mol Oncol)
Simultaneous treatment with dinaciclib and BH3 mimetics ABT-199 or A-1155463 additionally showed a synergistic effect in plasma cells from MM patients, ex vivo. Altered MM cytogenetics did not affect dinaciclib response ex vivo, alone or in combined treatment, suggesting that these combinations could be a suitable therapeutic option for patients bearing cytogenetic alterations and poor prognosis. This work also opens the possibility to explore cyclin-dependent kinase 9 (CDK9) inhibition as a targeted therapy in MM patients overexpressing or with high dependence on MCL-1.
Preclinical • Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1) • CDK9 (Cyclin Dependent Kinase 9) • CDK1 (Cyclin-dependent kinase 1)
|
MCL1 expression
|
Venclexta (venetoclax) • dinaciclib (MK-7965)
4ms
Synergistic cytotoxicity of decitabine and YM155 in leukemia cells through upregulation of SLC35F2 and suppression of MCL1 and survivin expression. (PubMed, Apoptosis)
Our data demonstrated that the synergistic cytotoxicity of DAC and YM155 in AML cell lines U937 and HL-60 is dependent on AKT- and p38 MAPK-mediated upregulation of SLC35F2 and p38 MAPK-mediated degradation of survivin and MCL1. This indicates that a treatment regimen that amalgamates YM155 and DAC may be beneficial for AML.
Journal
|
MCL1 (Myeloid cell leukemia 1) • PMAIP1 (Phorbol-12-Myristate-13-Acetate-Induced Protein 1) • SP1 (Sp1 Transcription Factor)
|
MCL1 expression • BIRC5 expression
|
decitabine • sepantronium bromide (PC-002)
4ms
The mechanism of anticancer effects of some pyrrolopyrimidine derivatives on HT-29 human colon cancer cells. (PubMed, Toxicol In Vitro)
Additionally, we found that proapoptotic BH3-only proteins BIM and PUMA are required for the full engagement of mitochondrial apoptosis signaling. However, p53 was dispensable for compound 5- or compound 8-induced apoptosis in HT-29 cells.
Journal
|
MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1) • BAX (BCL2-associated X protein) • CASP3 (Caspase 3) • BAK1 (BCL2 Antagonist/Killer 1) • BBC3 (BCL2 Binding Component 3)
|
MCL1 expression • BAX expression
4ms
The Effects of Resveratrol, Gallic Acid, and Piperine on the Expression of miR-17, miR-92b, miR-181a, miR-222, BAX, BCL-2, MCL-1, WT1, c-Kit, and CEBPA in Human Acute Myeloid Leukemia Cells and Their Roles in Apoptosis. (PubMed, Biochem Genet)
LNA-anti-miRs may be a promising agent for the treatment of AML. All three compounds used in this study showed anticancer effects, which can exert the desired outcome in patients with AML.
Journal • IO biomarker
|
KIT (KIT proto-oncogene, receptor tyrosine kinase) • BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1) • WT1 (WT1 Transcription Factor) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • BAX (BCL2-associated X protein) • MIR17 (MicroRNA 17) • MIR92B (MicroRNA 92b) • MIR181A1 (MicroRNA 181a-1) • MIR222 (MicroRNA 222)
|
BCL2 expression • MCL1 expression • KIT expression • BAX expression
4ms
Nuclear isoform of RAPH1 interacts with FOXQ1 to promote aggressiveness and radioresistance in breast cancer. (PubMed, Cell Death Dis)
These results collectively show that RAPH1-i3 interacts with FOXQ1 to promote breast cancer progression and radioresistance. RAPH1-i3 and FOXQ1 represent therapeutic targets for the treatment of breast cancer including TNBC.
Journal
|
ER (Estrogen receptor) • CCND1 (Cyclin D1) • BCL2L1 (BCL2-like 1) • MMP2 (Matrix metallopeptidase 2)
|
ER positive • MCL1 expression • CCND1 expression
4ms
Pharmacological mechanisms of norcantharidin against hepatocellular carcinoma. (PubMed, Am J Cancer Res)
In this article, we review recent progress in the application of NCTD for the treatment of HCC, with emphasis on the pharmacological mechanism of NCTD against hepatocellular carcinoma. The accumulated results show that NCTD has the ability to induce mitotic arrest, anti-proliferation, anti-metastasis, apoptosis and cytotoxic autophagy or autophagic cell death in HCC by down-regulating the expression of ISG15, MMP-9, u-PA, Mcl-1 and the accumulation of regulatory T cells, up-regulating the expression of FAM46C, miR-214 and the expression and phosphorylation of p21 and CDC25C, and by inhibiting the c-Met-mTOR and JAK/STAT3 signaling pathways, reversing the methylation of RASSF1A gene, and activating TRAIL-R2/DR5 signal transduction.
Review • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase) • MCL1 (Myeloid cell leukemia 1) • MMP9 (Matrix metallopeptidase 9) • CDC25C (Cell Division Cycle 25C) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • RASSF1 (Ras Association Domain Family Member 1) • TENT5C (Terminal Nucleotidyltransferase 5C) • TNFRSF10B (TNF Receptor Superfamily Member 10b) • GNRP (Ras-Specific Guanine Nucleotide-Releasing Factor 1) • ISG15 (ISG15 Ubiquitin Like Modifier) • MIR214 (MicroRNA 214)
|
MCL1 expression • RASSF1 methylation
4ms
Inhibitory actions of oxyresveratrol on the PI3K/AKT signaling cascade in cervical cancer cells. (PubMed, Biomed Pharmacother)
In consistent with these data, Oxy reduced the expression of β-catenin, N-cadherin, and vimentin. In conclusion, the study disclosed that Oxy specifically inhibits the AKT/GSK-3β/MCL-1 axis resulting in reduction in cervical cancer cell viability, proliferation, and migration.
Journal
|
CTNNB1 (Catenin (cadherin-associated protein), beta 1) • VIM (Vimentin) • TGFB1 (Transforming Growth Factor Beta 1) • CDH2 (Cadherin 2)
|
MCL1 expression • VIM expression
4ms
Hydroquinone-selected chronic myelogenous leukemia cells are sensitive to chloroquine-induced cytotoxicity via MCL1 suppression and glycolysis inhibition. (PubMed, Biochem Pharmacol)
Likewise, CQ-induced MCL1 suppression and glycolysis inhibition resulted in higher cytotoxicity in CML KU812/HQ cells than in KU812 cells. Taken together, our data confirm that CQ inhibits MCL1 expression through the ERK/miR-29a/TTP/NOXA pathway, and that inhibition of glycolysis is positively correlated to higher cytotoxicity of CQ on HQ-selected CML cells.
Journal
|
MCL1 (Myeloid cell leukemia 1) • MIR29A (MicroRNA 29a)
|
MCL1 overexpression • MCL1 expression
4ms
AZD4573 in Combination with CHOP Increases Combination Benefit in Preclinical Peripheral T-Cell Lymphomas Models (ASH 2023)
Current standard of care for pTCL revolves around the chemotherapy regimens CHOP/E and for CD30-postive pTCLs, brentuximab vedotin is approved...Using the MCL-1 inhibitor AZD5991, we have shown statistically significant benefit in survival when combined with CHOP in 2 MCL-1 dependent preclinical pTCL PDX models (Koch et al...These data suggested that treatment with AD4573 either as a monotherapy or in combination with CHOP, would be an effective therapeutic strategy in pTCL. AZD4573 monotherapy is currently being evaluated in a phase 2 study (NCT05140382) to assess the efficacy, safety, and PK in patients with relapsed/refractory pTCL.
Preclinical • Combination therapy • IO biomarker
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • TNFRSF8 (TNF Receptor Superfamily Member 8) • BCL2L1 (BCL2-like 1) • CASP3 (Caspase 3) • BCL2A1 (BCL2 Related Protein A1) • CASP7 (Caspase 7)
|
MYC overexpression • BCL2 expression • MCL1 expression
|
Adcetris (brentuximab vedotin) • AZD5991 • AZD4573
4ms
Correlation of Flow Cytometric BCL2 and MCL1 Expression with Cytogenetic Characteristics and Outcome in Multiple Myeloma (ASH 2023)
Our study demonstrates an objective assessment of BCL2 and MCL1 expression by FCM. BCL2 PC/T,MCL1 PC/T and BCL2 PC /MCL1 PC were significantly higher in myeloma cells compared to non-clonal PCs. Low MCL1 expression or high BCL2/MCL1 ratio was associated with IGH: : CCND1; while strong MCL1 and low BCL2/MCL1 ratio was most frequent in 1q21 amplification.
IO biomarker
|
TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • FGFR3 (Fibroblast growth factor receptor 3) • CCND1 (Cyclin D1) • MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1) • BCL2L2 (BCL2 Like 2) • BCL2L10 (BCL2 like 10) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
|
TP53 deletion • BCL2 expression • BCL2 positive • MCL1 expression
|
Venclexta (venetoclax)
4ms
Significance of the Apoptotic Regulators BAX, BCL2, BCL- XL and MCL1 in Newly Diagnosed AML (ASH 2023)
Standard chemotherapy (induction therapy with idarubicin and cytarabine (7+3) and consolidation therapy with high dose cytarabine) was used in 98...However, venetoclax appears to have limited activity as a single agent. For the correlative survival analyses, Bax, Bcl2, Bcl-xL and Mcl1 mRNA expression and clinical information were both obtained from the BeatAML cohort 1. Patients were categorized into high expressers (≥ median) and low expressers (<median). In total, 461 patients had available gene expression data.
IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • NPM1 (Nucleophosmin 1) • MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1) • BAX (BCL2-associated X protein)
|
NPM1 mutation • MCL1 expression • BAX expression
|
Venclexta (venetoclax) • cytarabine • idarubicin hydrochloride
4ms
Dihydroartemisinin Synergistically Promotes the Antileukemic Activity of Venetoclax By Downregulating Mcl-1 in Acute Myeloid Leukemia Cells (ASH 2023)
For older persons with newly diagnosed AML, the FDA has approved the use of venetoclax in conjunction with hypomethylating drugs or low-dose cytarabine. Our findings demonstrate the synergistic, preferential antileukemic effects of venetoclax and DHA on AML cells, providing a rationale for preclinical and clinical trials by combining these agents already being used in clinical practice to treat AML.
IO biomarker
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1)
|
MYC expression • MCL1 expression
|
Venclexta (venetoclax) • cytarabine
4ms
Combined Inhibition of Protein Kinase CSNK2 and BET Proteins As a Novel Therapeutic Strategy for Mantle Cell Lymphoma (ASH 2023)
Currently available therapeutic approaches for Mantle Cell Lymphoma (MCL), including the Bruton Tyrosine Kinase (BTK) inhibitors ibrutinib, acalabrutinib and zanubrutinib, are not curative...In MCL, BET inhibitors, such as INCB054329 or JQ-1, have been shown to increase apoptosis through downregulation of the AKT-mTOR, ERK, and other B Cell Receptor (BCR)-triggered cascades...The most effective and tested CSNK2 chemical inhibitor is CX4945 (silmitasertib), but very recently a novel compound, SGC-CK2, has been developed...Remarkably, CK2 inactivation led to a robust reduction of the BET inhibitor-induced increase of Mcl1, and NF-kB Ser 529 phosphorylation, thus counteracting BET-inhibitors-evoked compensatory pathways that could favor apoptosis resistance. Therefore, combined CSNK2 and BET proteins inhibition could represent an innovative strategy for chemotherapy and BTKi-resistant MCL.
PARP Biomarker
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BRD4 (Bromodomain Containing 4) • ANXA5 (Annexin A5)
|
MCL1 expression
|
Imbruvica (ibrutinib) • Brukinsa (zanubrutinib) • Calquence (acalabrutinib) • JQ-1 • silmitasertib (CX-4945) • INCB054329