ArticleNature communications2019
Destabilization of NOXA mRNA as a common resistance mechanism to targeted therapies.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 80 citations in OpenAlex.
- BH3 profiling analyses for functional precision medicine.Oncogenesis · 2026Review
- Decoding the Raf-Mek-Erk-Rsk pathway in prostate cancer: from molecular mechanisms to clinical opportunities.British journal of cancer · 2026Review
- NOXA/MCL-1 axis determines cell-death decision between apoptosis and a GSDME-dependent cell death associated with production of inflammatory cytokines upon treatment of breast cancer cells with antimitotics.Cell death & disease · 2026Article
- Targeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies.International journal of molecular sciences · 2025Review
- PMAIP1 mediates endoplasmic reticulum stress in human dental pulp stem cells during pulpitis pathogenesis.BMC oral health · 2025Article
- Expression profiling of KRAS and NOXA genes as prospective biomarkers in ovarian carcinoma.Scientific reports · 2025Article
- Myeloid EGFR deficiency accelerates recovery from AKI via macrophage efferocytosis and neutrophil apoptosis.Nature communications · 2025Article
- HRK downregulation and augmented BCL-xL binding to BAK confer apoptotic protection to therapy-induced senescent melanoma cells.Cell death and differentiation · 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
- Low BCL-xL expression in triple-negative breast cancer cells favors chemotherapy efficacy, and this effect is limited by cancer-associated fibroblasts.Scientific reports · 2024Article
- Eugenol as a potential adjuvant therapy for gingival squamous cell carcinoma.Scientific reports · 2024Article
- Combinatorial strategies to target RAS-driven cancers.Nature reviews. Cancer · 2024Review
- Small molecule Mcl-1 inhibitor for triple negative breast cancer therapy.Frontiers in cell and developmental biology · 2024Review
- Article
- Analysis of differential membrane proteins related to matrix stiffness-mediated metformin resistance in hepatocellular carcinoma cells.Proteome science · 2023Article
- Bcl-2 family inhibitors sensitize human cancer models to therapy.Cell death & disease · 2023Article
- Anticancer genes (NOXA, PAR-4, TRAIL) are de-regulated in breast cancer patients and can be targeted by using a ribosomal inactivating plant protein (riproximin).Molecular biology reports · 2023Article
- Enhanced Apoptosis and Loss of Cell Viability in Melanoma Cells by Combined Inhibition of ERK and Mcl-1 Is Related to Loss of Mitochondrial Membrane Potential, Caspase Activation and Upregulation of Proapoptotic Bcl-2 Proteins.International journal of molecular sciences · 2023Article
- Transient targeting of BIM-dependent adaptive MCL1 preservation enhances tumor response to molecular therapeutics in non-small cell lung cancer.Cell death and differentiation · 2023Article
- Microfluidic-based dynamic BH3 profiling predicts anticancer treatment efficacy.NPJ precision oncology · 2022Article
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Most targeted cancer therapies fail to achieve complete tumor regressions or attain durable remissions. To understand why these treatments fail to induce robust cytotoxic responses despite appropriately targeting oncogenic drivers, here we systematically interrogated the dependence of cancer cells on the BCL-2 family of apoptotic proteins after drug treatment. We observe that multiple targeted therapies, including BRAF or EGFR inhibitors, rapidly deplete the pro-apoptotic factor NOXA, thus creating a dependence on the anti-apoptotic protein MCL-1. This adaptation requires a pathway leading to destabilization of the NOXA mRNA transcript. We find that interruption of this mechanism of anti-apoptotic adaptive resistance dramatically increases cytotoxic responses in cell lines and a murine melanoma model. These results identify NOXA mRNA destabilization/MCL-1 adaptation as a non-genomic mechanism that limits apoptotic responses, suggesting that sequencing of MCL-1 inhibitors with targeted therapies could overcome such widespread and clinically important resistance.
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Registered trials
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.