ArticleCancer discovery2018
Exploiting MCL1 Dependency with Combination MEK + MCL1 Inhibitors Leads to Induction of Apoptosis and Tumor Regression in
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Article in Cancer discovery, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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55citing papers in PubMed
4.4field-weighted citation impact, top 4% of its field
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Who cites it
55 citing papers in PubMed, 91 citations in OpenAlex.
- Targeting MCL-1 to Overcome Therapeutic Resistance and Improve Cancer Mortality.Health science reports · 2025Article
- Function ofOncology letters · 2025Review
- LKB1 regulates JNK-dependent stress signaling and apoptotic dependency of KRAS-mutant lung cancers.Nature communications · 2025Article
- Diselenide-based nanoparticles enhancing the radioprotection to the small intestine of mice.Journal of nanobiotechnology · 2025Article
- Novel selective strategies targeting the BCL-2 family to enhance clinical efficacy in ALK-rearranged non-small cell lung cancer.Cell death & disease · 2025Article
- Detecting Small Cell Transformation in Patients with Advanced EGFR Mutant Lung Adenocarcinoma through Epigenomic cfDNA Profiling.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Discovery of a Myeloid Cell Leukemia 1 (Mcl-1) Inhibitor That Demonstrates PotentJournal of medicinal chemistry · 2024Article
- Combinatorial strategies to target RAS-driven cancers.Nature reviews. Cancer · 2024Review
- Potential biomarkers for MCL1 inhibitor sensitivity.Cell signaling · 2024Article
- PBRM1 loss is associated with increased sensitivity to MCL1 and CDK9 inhibition in clear cell renal cancer.Frontiers in oncology · 2024Article
- eIF4A dependency: the hidden key to unlock KRAS mutant non-small cell lung cancer's vulnerability.Translational lung cancer research · 2023Article
- Increased MCL1 dependency leads to new applications of BH3-mimetics in drug-resistant neuroblastoma.British journal of cancer · 2023Article
- Cotargeting a MYC/eIF4A-survival axis improves the efficacy of KRAS inhibitors in lung cancer.The Journal of clinical investigation · 2023Article
- USP9X mediates an acute adaptive response to MAPK suppression in pancreatic cancer but creates multiple actionable therapeutic vulnerabilities.Cell reports. Medicine · 2023Article
- Lymphoma cells lacking pro-apoptotic BAX are highly resistant to BH3-mimetics targeting pro-survival MCL-1 but retain sensitivity to conventional DNA-damaging drugs.Cell death and differentiation · 2023Article
- Synthetic Lethal Interaction with BCL-XL Blockade Deepens Response to Cetuximab in Patient-Derived Models of Metastatic Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- BCL-2 protein family: attractive targets for cancer therapy.Apoptosis : an international journal on programmed cell death · 2023Review
- Endogenous and imposed determinants of apoptotic vulnerabilities in cancer.Trends in cancer · 2023Review
- Genotype-Tailored ERK/MAPK Pathway and HDAC Inhibition Rewires the Apoptotic Rheostat to Trigger Colorectal Cancer Cell Death.Molecular cancer therapeutics · 2023Article
- Targeting MCL-1 protein to treat cancer: opportunities and challenges.Frontiers in oncology · 2023Review
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Authors and funding
30 authors at 3 institutions in 1 country.
Varuna Nangia *Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts.
Faria M Siddiqui *Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts.
Sean CaenepeelDepartment of Oncology Research, Amgen, Thousand Oaks, California.
Daria TimoninaMassachusetts General Hospital Cancer Center, Charlestown, Massachusetts.
Samantha J BiltonMassachusetts General Hospital Cancer Center, Charlestown, Massachusetts.
Nicole PhanMassachusetts General Hospital Cancer Center, Charlestown, Massachusetts.
Maria Gomez-CaraballoMassachusetts General Hospital Cancer Center, Charlestown, Massachusetts.
Hannah L ArchibaldMassachusetts General Hospital Cancer Center, Charlestown, Massachusetts.
Chendi LiMassachusetts General Hospital Cancer Center, Charlestown, Massachusetts.
Cameron FraserDepartment of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
Diamanda RigasDepartment of Oncology Research, Amgen, Thousand Oaks, California.
Kristof VajdaMassachusetts General Hospital Cancer Center, Charlestown, Massachusetts.
Lorin A FerrisMassachusetts General Hospital Cancer Center, Charlestown, Massachusetts.
Michael LanutiDepartment of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
Cameron D WrightDepartment of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
Kevin A RaskinDepartment of Orthopaedics, Massachusetts General Hospital, Boston, Massachusetts.
Daniel P CahillDepartment of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.
John H ShinDepartment of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.
Colleen KeyesDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Lecia V SequistDivision of Hematology Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0002-8965-6991
Zofia PiotrowskaDivision of Hematology Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Anna F FaragoDivision of Hematology Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Christopher G AzzoliDivision of Hematology Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Justin F GainorDivision of Hematology Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Kristopher A SarosiekDepartment of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
Sean P BrownDepartment of Medicinal Chemistry, Amgen, Thousand Oaks, California.ORCID 0000-0002-8218-002X
Angela CoxonDepartment of Oncology Research, Amgen, Thousand Oaks, California.
Cyril H BenesMassachusetts General Hospital Cancer Center, Charlestown, Massachusetts.ORCID 0000-0002-8751-9707
Paul E HughesDepartment of Oncology Research, Amgen, Thousand Oaks, California.
Aaron N HataMassachusetts General Hospital Cancer Center, Charlestown, Massachusetts. ahata@mgh.harvard.edu.
Massachusetts General Hospital · USHarvard University · USAmgen (United States) · US
Funding
Therapeutic strategies for specific subsets of KRAS mutant lung cancersR01CA140594 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI WONG, KWOK KIN · 2009 to 2017
$4.5MRegulation of Apoptotic Priming and Competence in Healthy and Cancerous CellsR00CA188679 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI SAROSIEK, KRISTOPHER ANDREW · 2017 to 2019
$747kNCI NIH HHS R00 CA188679NCI NIH HHS R01 CA140594
Abstract
BH3 mimetic drugs, which inhibit prosurvival BCL2 family proteins, have limited single-agent activity in solid tumor models. The potential of BH3 mimetics for these cancers may depend on their ability to potentiate the apoptotic response to chemotherapy and targeted therapies. Using a novel class of potent and selective MCL1 inhibitors, we demonstrate that concurrent MEK + MCL1 inhibition induces apoptosis and tumor regression in
Indexed as
A549 CellsAniline CompoundsAnimalsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBenzamidesCarcinoma, Non-Small-Cell LungCell Line, TumorDiphenylamineHumansLung NeoplasmsMice, KnockoutMice, NudeMice, SCIDMitogen-Activated Protein Kinase KinasesAniline CompoundsAntineoplastic AgentsBenzamidesDiphenylamineKRAS protein, humanmirdametinibMitogen-Activated Protein Kinase KinasesMyeloid Cell Leukemia Sequence 1 ProteinnavitoclaxProtein Kinase InhibitorsProto-Oncogene Proteins p21(ras)Sulfonamides
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.