- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, S63845 / Servier, Novartis, Ligand, A-1331852 / AbbVie
[VIRTUAL] Anti-apoptotic proteins BCL-XL and MCL-1 are crucial for nasopharyngeal carcinoma (NPC) cell survival (Virtual Meeting II: E-Posters) - May 16, 2020 - Abstract #AACRII2020AACR-II_3224;
However, the effect of the combination was not as pronounced as combination of A1331852 and S63845. Collectively, our data demonstrate that BCL-XL and MCL-1 are crucial for NPC survival and targeting these proteins with selective inhibitors may be potentially useful as treatment strategies for the management of NPC.
- |||||||||| pimasertib (AS703026) / EMD Serono, Sanofi
Mechanism of MEK inhibitor resistance in triple negative breast cancer (Virtual Meeting II: E-Posters) - May 16, 2020 - Abstract #AACRII2020AACR-II_3123;
We found preliminary evidence of a link between Mcl-1 and glycolytic metabolism that may be involved in MEK resistance. We will also design combinational studies of MEKi and Mcl-1 inhibitors in vivo in TNBC models.
- |||||||||| paclitaxel / Generic mfg., doxorubicin hydrochloride / Generic mfg.
Investigations of drug synergy reveal promising efficacy of EphA2 inhibition combined with CDK inhibition in triple-negative breast cancer (Virtual Meeting II: E-Posters) - May 16, 2020 - Abstract #AACRII2020AACR-II_2472;
Furthermore, genetic knockdown or inhibition of EphA2 with the small molecule ALW-II-41-27 (ALW) reduces cancer cell growth in vitro and in vivo...To this end, TNBC lines MDA-MB-231, BT-549, HCC1395, and HCC1187 were seeded in 96-well plates and exposed to ALW alone or in combination with chemotherapeutic agents doxorubicin and paclitaxel, CDK inhibitor SCH-727965, and MCL-1 inhibitor S63845 and cell viability assessed by MTT assay at 48 hours...Furthermore, TUNEL assays show that addition of SCH-727965 to ALW significantly increases the induction of apoptosis by HCC1395 and HCC1187 cells. These preclinical studies demonstrate that combination of ALW and SCH-727965 potently reduces TNBC cell growth and promotes cell death, representing promising early data on the effects of EphA2 inhibition as part of a combination targeted therapeutic approach for triple-negative breast cancer.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, S63845 / Servier, Novartis, Ligand
[VIRTUAL] INHIBITION OF THE ANTI-APOPTOTIC PROTEIN MCL-1 SEVERELY SUPPRESSES HUMAN HEMATOPOIESIS () - May 16, 2020 - Abstract #EHA2020EHA_1225;
While the BCL-2 inhibitor Venetoclax is already FDA-approved, BCL-XL and MCL-1 inhibitors are currently in early clinical trials...MCL-1 inhibition in cord-blood derived CD34+ cells was achieved by shRNA and the small molecule drug S63845...Our findings are relevant for clinical use of MCL-1 inhibitors considering that hematological side effects are responsible for most treatment-related morbidity and mortality of anticancer therapies. Importantly, “synthetic lethality” of two BH3-mimetics is not restricted to malignant cells but affects also healthy hematopoietic progenitors.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie
[VIRTUAL] A NOVEL MECHANISM OF VENETOCLAX RESISTANCE IN ACUTE MYELOID LEUKEMIA: DELETION OF BAX () - May 16, 2020 - Abstract #EHA2020EHA_714;
It recently received accelerated US FDA approval for use in combination with hypomethylating agents or with low-dose cytarabine in elderly or unfit acute myeloid leukemia (AML) patients...The MV4-11 ABT-199R clones also demonstrated co-resistance to ABT-737 (BCL-2 and BCL-XL inhibitor), S63845 (MCL-1 inhibitor), and S55746 (BCL-2 inhibitor)...As a result of BAX gene deletion, the inhibitors of BCL-2, BCL-XL, and MCL-1 are rendered ineffective in inducing apoptosis. Alternative mechanisms of apoptosis induction need to be explored to overcome BAX deletion-induced resistance.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie
[VIRTUAL] CHARACTERIZATION OF MECHANISMS OF ACQUIRED VENETOCLAX-INSENSITIVITY IN B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA () - May 16, 2020 - Abstract #EHA2020EHA_615;
Upon S63845 exposure, the pro-apoptotic protein BIM is released from MCL-1 but sequestered by BCL-2.By co-targeting BCL-2 and MCL-1 with VEN and the specific MCL-1 inhibitor S63845 we could synergistically induce cell death in the VEN insensitive lines by releasing BIM from both BCL-2 and MCL-1. Conclusion Taken together, we show that acquired VEN resistance in BCP-ALL is characterized by up-regulated expression of counter-regulatory MCL-1 and can be overcome by simultaneous BCL-2 and MCL-1 inhibition, which prevents sequestration of BIM by MCL-1 after release from BCL-2.
- |||||||||| [VIRTUAL] THE SEARCH FOR OPTIMIZATION STRATEGIES OF MCL-1 INHIBITORS IN MULTIPLE MYELOMA HIGHLIGHTS CONCURRENT BCL-XL TARGETING AND ABCB1 BLOCKADE AS PROMISING THERAPEUTIC STRATEGIES () - May 16, 2020 - Abstract #EHA2020EHA_520;
Accordingly, venetoclax in combination with S63845 demonstrated strong synergism in KMS12BM but not OPM2 cells, where the concurrent use of Bcl-xL inhibitors demonstrated strong synergism...Finally, we examined the impact of prior PI exposure on the efficacy of MCL1 inhibitors and indeed observed a complete loss of S63845 and A-1210477 activity in carfilzomib, but not ixazomib resistant cells...Moreover, our findings suggest that different baseline BH3 profiles guide alternative routes to acquired MCL1 inhibitor drug resistance and reveal S63845 as a novel MDR1 substrate. This underlines the importance of identifying clone specific adaptations and the need for careful selection of drug combinations for individualized treatment approaches.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, S63845 / Servier, Novartis, Ligand, navitoclax (ABT 263) / AbbVie, Roche
Preclinical, Journal: Co-inhibition of BCL-XL and MCL-1 with selective BCL-2 family inhibitors enhances cytotoxicity of cervical cancer cell lines. (Pubmed Central) - Apr 30, 2020
Treatment with a combination of A1331852 and S63845 resulted in inhibition of growth and invasion of the 3D spheroids. Collectively, our data demonstrate that the combination of MCL-1-selective inhibitors with either selective inhibitors of either BCL-XL or BCL-2 may be potentially useful as treatment strategies for the management of cervical cancer.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, S63845 / Servier, Novartis, Ligand
Journal: Combined Bcl-2/Src inhibition synergize to deplete stem-like breast cancer cells. (Pubmed Central) - Apr 29, 2020
In contrast, the Mcl-1 inhibitor S63845 potently targeted basal-like, but not stem-like cells, highlighting dependency on distinct sentinel Bcl-2 family members. Our findings reveal Bcl-2/Src inhibition as a superior therapy to target stemness, providing a foundation for a potential personalized strategy to reduce breast cancer progression.
- |||||||||| S63845 / Servier, Novartis, Ligand
Journal: Targeting Mcl-1 inhibits survival and self-renewal of hepatocellular cancer stem-like cells. (Pubmed Central) - Apr 22, 2020
Inhibition of Mcl-1 by specific inhibitors S63845 or A-1210477 hindered secondary sphere formation, triggered apoptosis signaling and reduced the level of stem cell transcription factor Nanog, Sox2 and KLF4 in HCC spheroids cells. This study suggests that Mcl-1 is an essential factor for the survival and self-renewal of HCC CSLCs.
- |||||||||| doxorubicin hydrochloride / Generic mfg., cyclophosphamide intravenous / Generic mfg., Rituxan (rituximab) / Roche, Biogen, Zenyaku Kogyo
Journal, Heterogeneity, IO Biomarker: Heterogeneous Pattern of Dependence on Anti-Apoptotic BCL-2 Family Proteins upon CHOP Treatment in Diffuse Large B-Cell Lymphoma. (Pubmed Central) - Apr 17, 2020
Expression of the anti-apoptotic B-cell lymphoma 2 (BCL-2) protein in patients with diffuse large B-cell lymphoma (DLBCL) strongly correlates with resistance to standard therapy with cyclophosphamide, vincristine, doxorubicin, prednisolone, and rituximab (R-CHOP)...In conclusion, we show for the first time that CHOP treatment induces increased anti-apoptotic dependency on MCL-1 and BCL-XL, and not just BCL-2. These results provide new perspectives for the treatment of CHOP-resistant DLBCL and underline the potential of BH3 profiling in predicting therapy outcomes.
- |||||||||| S63845 / Servier, Novartis, Ligand, navitoclax (ABT 263) / AbbVie, Roche
Review, Journal: Targeting Mcl-1 and Other Bcl-2 Family Member Proteins in Cancer Therapy. (Pubmed Central) - Mar 26, 2020
One way to address the safety issue is by limiting exposure to all the agents to only cancer cells, thus making the combination safe and effective. In this article, we review this rapidly developing idea in cancer research.
- |||||||||| S63845 / Servier, Novartis, Ligand, idasanutlin (RO5503781) / Roche, AZD5991 / AstraZeneca
Towards first-in-class dual Mcl-1/HDM2 PROTACs to treat hematological malignancies (Exhibit Hall D, Pennsylvania Convention Center) - Feb 13, 2020 - Abstract #ACSSp2020ACS_Sp_16587;
Therefore, since HDM2 is an E3 ligase, it is hypothesized that bivalent Mcl-1/HDM2 inhibitors will inherently function as PROTACs as well. We will present our progress towards first-in-class dual Mcl-1/HDM2 PROTACs, including their evaluation in AML and MM cancer cell lines.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, S63845 / Servier, Novartis, Ligand
Targeting antiapoptotic proteins Bcl-xL and Mcl-1 in cholangiocarcinoma (ePoster Area) - Jan 27, 2020 - Abstract #EASLHCC2020EASL_HCC_92;
Combined treatment of Wehi-539 with S63645 showed a highly synergistic cell death inducing effect in CCA cells. This promising concept might be translated in clinical studies.
- |||||||||| S63845 / Servier, Novartis, Ligand, navitoclax (ABT 263) / AbbVie, Roche
The role of BH-3 mimetic drugs in overcoming immunotherapy resistance in melanoma (Trade Area Level 2&3) - Jan 24, 2020 - Abstract #LCC2020LCC_110;
These data suggest that the integration of BH3 mimetics with immune checkpoint inhibitors may prove effective in overcoming immunotherapy resistance in melanoma. Further work on response mechanisms is currently under investigation in our group.
- |||||||||| S63845 / Servier, Novartis, Ligand, navitoclax (ABT 263) / AbbVie, Roche
BH3 mimetics as promising treatment options for Melanoma () - Nov 21, 2019 - Abstract #SMR2019SMR_267;
In tumor cells isolated from these mice, the combination treatments had significantly lower sphere forming capacity compared to single drugs (p < 0.05), supporting the idea that the combinations kill MICs. In summary, data strongly suggest combinations targeting MCL1 and BCLXL is an alternate treatment option for melanoma.
- |||||||||| Journal: WEE1 Inhibition Enhances Anti-Apoptotic Dependency as a Result of Premature Mitotic Entry and DNA Damage. (Pubmed Central) - Nov 11, 2019
In addition, we demonstrate that both G2/M cell cycle arrest and DNA damage induction put a similar stress on DLBCL cells, thereby enhancing anti-apoptotic dependency. Therefore, genotoxic or cell cycle disrupting agents combined with specific anti-apoptotic inhibitors may be very effective in genomic unstable cancers such as DLBCL and therefore warrants further clinical evaluation.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, S63845 / Servier, Novartis, Ligand
CRISPR-Cas9 Screen Identifies Me2, a Mitochondrial Malic Enzyme, As a Molecule Relevant for MCL1 Inhibitor Resistance in AML (W308, Level 3 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_6578;
In conclusion, using an unbiased, genome-wide CRISPR/Cas9 screens, we identified Me2, a mitochondrial metabolic enzyme, as a factor relevant for MCL1 inhibitor resistance . Our study may facilitate the understanding of molecular mechanisms underlying acquired resistance to MCL1 inhibitors in AML.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, dexamethasone / Generic mfg., S63845 / Servier, Novartis, Ligand
Statins Enhance Killing of Multiple Myeloma Cells By the BCL-2 Inhibitor Venetoclax and the MCL-1 Inhibitor S63845 (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_6160;
However, there is a continuing need to develop safe and effective combinations in multiple myeloma (MM), where the BELLINI triple combination trial (venetoclax-dexamethasone-bortezomib) was closed to accrual due to adverse events...In OPM2 cells, pitavastatin synergizes with venetoclax and increases apoptosis in triple combination with dexamethasone...Statin-induced apoptosis and PUMA expression are rescued by addition of geranylgeranyl-pyrophosphate, and recapitulated by an inhibitor of geranylgeranyl-transferase I. Together these findings establish a mechanistic framework to explain how statins promote apoptosis by BH3 mimetic drugs like venetoclax and S63845. Further, these results highlight the potential of statins to enhance therapeutic efficacy of BCL-2 and MCL-1 inhibitor regimens in MM, with possibly lesser toxicity than other combination strategies.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie
Characterization of Mechanisms of Acquired Venetoclax-Insensitivity in B-Cell Precursor Acute Lymphoblastic Leukemia (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_5685;
This indicates that co-targeting MCL-1 can block the sequestration of pro-apoptotic BIM from BCL-2 to MCL-1, overcoming VEN resistance . Taken together, we show that acquired VEN resistance in BCP-ALL is characterized by up-regulated expression of counter-regulatory MCL-1 and can be overcome by simultaneous BCL-2 and MCL-1 inhibition, which prevents sequestration of BIM by MCL-1 after release from BCL-2.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie
Mutations and Copy Number Gains of the BCL2 Family Members Mediate Resistance to Venetoclax in Multiple Myeloma (MM) Patients (W224CDGH, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_4779;
In addition we have identified through single cell profiling an enrichment of MM clones with MCL1 locus copy number gain at the time of acquired venetoclax resistance. Early detection and dynamic monitoring of these abnormalities (BCL2 mutant or 1q gain) with early therapeutic interventions targeting these clones may enhance venetoclax efficacy and improve patients' survival.
- |||||||||| Mcl-1 inhibitors / Vanderbilt University
Variable Response to BCL2 Inhibition in MDS Is Enhanced across MDS Subtypes with Synergistic Combination of BCL2+MCL1 Inhibition (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_4171;
Venetoclax (VEN), a newly FDA-approved therapy that specifically inhibits the anti-apoptotic protein BCL2, has yielded response rates of up to 50-70% in elderly AML including impressive responses in transformed MDS which previously failed DNMTi (DiNardo et al, 2019, Wei et al, 2019)...Interestingly, nearly all MDS subtypes were sensitive to the selective MCL1 inhibitor, S63845...Moreover, drug synergy can be obtained across all subtypes of MDS by combining BCL2 and MCL1 inhibitors . BCL2 inhibition is changing the standard of care in AML, thus, refining the design of clinical trials testing BCL2 and MCL1 inhibitors in MDS and the precision of patient selection for therapy is a great priority.
- |||||||||| azacitidine / Generic mfg.
Individualized Mitochondrial Functional Approach to Combination of BCL-2 and MCL-1 Antagonism in Acute Myeloid Leukemia (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_3720;
BCL-2 antagonist venetoclax combined with hypomethylating agents or low-dose cytarabine is a new standard of care for treatment-naive elderly or unfit AML patients...By using pretreatment myeloblasts of patients (N=16) from clinical trial of venetoclax and azacitidine, we found that response to HRK + MS1 peptides (infers BCL-XL and MCL-1 dependency, respectively) inversely correlates with the achievement of remission...First, we exposed 6 AML cell lines with a BCL-2 (venetoclax) and MCL-1 antagonist (S63845)...Although venetoclax resistant cells gained cross resistance to most of the agents, inhibitors of the FLT-3 pathway, including quizartinib, crenolanib, and gilteritinib retained similar priming responses as in parental cells...In conclusion, our study illustrates the power of mitochondrial measurements as a predictive biomarker for BH3 mimetic based therapy. We provide an evidence for the persistent activity of FLT-3 inhibitors in venetoclax resistance settings, a discovery made possible by dynamic BH3 profiling.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, S63845 / Servier, Novartis, Ligand
Dual Inhibition of MCL1 and BCL2 in Lymphoma Using Tumor Targeted Nanoparticles (Valencia A (W415A), Level 4 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_1690;
When combination therapy was administered with one drug encapsulated as a nanoparticle, we did not observe significant weight loss or hematological toxicity, demonstrating that this nanoparticle delivery platform can deliver therapeutic drug concentration to tumor cells while sparing normal cells from treatment toxicity . This is the first study to demonstrate the potential therapeutic value of targeted BH3 mimetics nanoparticles in lymphoma.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, S63845 / Servier, Novartis, Ligand
Journal: Selective BH3-mimetics targeting BCL-2, BCL-XL or MCL-1 induce severe mitochondrial perturbations. (Pubmed Central) - Oct 2, 2019
Specifically, the selective BH3-mimetics ABT-199, A-1331852 and S63845, which target BCL-2, BCL-XL and MCL-1, respectively, induce comparable ultrastructural changes including mitochondrial swelling, a decrease of mitochondrial matrix density and severe loss of cristae structure. These shared effects on mitochondrial morphology indicate a similar function of these anti-apoptotic BCL-2 proteins in maintaining mitochondrial integrity and function.
- |||||||||| paclitaxel / Generic Mfg.
Mitosis leakage and Mcl1 inhibition as a therapeutic approach in solid tumors (M8) - Sep 30, 2019 - Abstract #DGHO2019DGHO_1536;
In NSCLC highly efficient mitotic arrest with subsequent apoptosis in mitosis was reached by combining an antimitotic agent and a direct APC/C-inhibitor, blocking cyclin B-proteolysis and mitotic exit using low doses achievable in vivo. A similar effect was reached with the combination with an unspecific PI.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, S63845 / Servier, Novartis, Ligand, AZD5991 / AstraZeneca
A focused RNAi screen identifies MCL1 as a potent therapeutic target in mantle cell lymphoma (M8) - Sep 30, 2019 - Abstract #DGHO2019DGHO_957;
In summary, using an unbiased shRNA screen of more than 300 genes contained in the PI3K pathway, we were able to identify a range of novel targets in Cyclin D1 driven lymphoma cells. The BCL2 family member MCL1 emerged from the screen as a potent vulnerability in our MCL model, and subsequent preclinical testing in primary tumors and human MCL cell lines using 2 small molecule inhibitors confirmed MCL1 inhibition as a promising new therapeutic approach in MCL.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, S63845 / Servier, Novartis, Ligand, ABT-737 / AbbVie
The importance of BCL-2 family proteins in patients with hypereosinophilia (M3) - Sep 30, 2019 - Abstract #DGHO2019DGHO_577;
In contrast to our previous understanding eosinophils extracted from patients with hypereosinophilic disorders show clear differences in their apoptotic threshold and their capability to undergo apoptosis compared to healthy controls. Here, BIM seems to be a critical regulator.
- |||||||||| S63845 / Servier, Novartis, Ligand
THERAPEUTIC TARGETING OF DUCTULAR REACTIVE CELLS IN CHOLESTATIC LIVER DISEASE (Hynes Convention Center, Room 210) - Sep 29, 2019 - Abstract #AASLD2019AASLD_756;
DR cells are sensitive to apoptosis by a MCL-1 dependent mechanism. Pharmacologic targeting of MCL-1 in mouse model of chronic cholestasis reduces DR cell population and hepatic fibrosis, suggesting this therapy may be useful in human cholestatic liver disease.
- |||||||||| S63845 / Servier, Novartis, Ligand
THERAPEUTIC MODULATION OF THE DUCTULAR REACTION AS A CHEMOPREVENTATIVE STRATEGY AGAINST LIVER CANCER () - Sep 20, 2019 - Abstract #ILCA2019ILCA_135;
Importantly, MCL-1 inhibition in vivo results in attenuation of ductular reaction in a mouse model of chronic cholestatic liver injury. We conclude that apoptosis of ductular reactive cells in chronic cholestatic liver disease can serve as a potential target for intervention to protect against the development of hepatic fibrosis and liver cancer.
- |||||||||| S63845 / Servier, Novartis, Ligand, Rydapt (midostaurin) / Novartis
Synergistic Activity of the MCL-1 Inhibitor S63845 with Midostaurin in Preclinical Human Models of FLT3-ITD Mutated Acute Myeloid Leukemia (AML) (Acute Myeloid Leukemia) - Aug 18, 2019 - Abstract #SOHO2019SOHO_110;
Here, we show that S63845 elicited synergistic activity with FLT3 inhibitors AC220, sorafenib and with a multi-kinase inhibitor midostaurin in pre-clinical models of AML.Results S63845 had potent single agent activity in AML cell lines and primary FLT3-ITD samples with IC50 values in low nanomolar range...Given that Mcl-1 is commonly upregulated in AML which acquired resistance to Bcl-2 inhibitor venetoclax, we also tested the efficacy of S63845/midostaurin combination in venetoclax-resistant MOLM-13 FLT3-ITD cells generated by exposure to gradually increasing doses of venetoclax in culture...We found that S63845 alone was ∼ 8 times more active in resistant cells, confirming their dependency on Mcl-1 for survival. Importantly, the S63845 and midostaurin synergy was clearly observed in venetoclax-resistant cells, which points to a novel therapeutic strategy overcoming this type of resistance.Conclusions S63845/midostaurin combination is highly effective in FLT3-ITD mutated AML cells including those resistant to venetoclax.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, S55746 / Novartis, S63845 / Servier, Novartis, Ligand
Journal, IO Biomarker: Combining BH3-Mimetics to target both BCL-2 and MCL1 has potent activity in pre-clinical models of acute myeloid leukemia. (Pubmed Central) - Aug 11, 2019
In conclusion, a dual BH3-mimetic approach is feasible, highly synergistic, and active in diverse models of human AML. This approach has strong clinical potential to rapidly suppress leukemia, with reduced toxicity to normal hematopoietic precursors compared to chemotherapy.
- |||||||||| cyclophosphamide intravenous / generics
Journal: Humanized Mcl-1 mice enable accurate pre-clinical evaluation of MCL-1 inhibitors destined for clinical use. (Pubmed Central) - Jul 24, 2019
When huMcl-1;Eµ-Myc lymphoma cells were transplanted into huMcl-1 mice, treatment with S63845 alone or alongside cyclophosphamide led to long-term remission in ~60% or almost 100% of mice, respectively. These results demonstrate the potential of our huMCL-1 mouse model for testing MCL-1 inhibitors, allowing precise predictions of efficacy and tolerability for clinical translation.
- |||||||||| S63845 / Servier, Novartis, Ligand
Journal, IO Biomarker: Increased MCL-1 expression predicts poor prognosis and disease recurrence in acute myeloid leukemia. (Pubmed Central) - May 25, 2019
...Recently, MCL-1 inhibitor S63845 was reported to kill MCL-1-dependent cancer cells and has potential value in clinical application...In follow-up patients, MCL-1 expression level decreased after CR compared with newly diagnosis time (P=0.020) and increased after relapse (P=0.004). Our findings suggest that higher expression of MCL-1 predicts poor prognosis and can be used for disease monitoring.
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