MYC proto-oncogene (MYC)
MYC (c-Myc) is a nuclear phosphoprotein that acts as a sequence-specific transcription factor and ranks among the most frequently deregulated oncoproteins in human cancer.
MYC (c-Myc) is a nuclear phosphoprotein that acts as a sequence-specific transcription factor and ranks among the most frequently deregulated oncoproteins in human cancer. It belongs to the basic helix-loop-helix leucine-zipper (bHLH-LZ) class of DNA-binding proteins and is the product of the MYC proto-oncogene on chromosome 8q24. On its own MYC has little transcriptional activity; it must heterodimerize with its obligate partner MAX to bind E-box motifs at target promoters and enhancers, where it recruits coactivator and chromatin-modifying complexes. Through this activity MYC drives broad programs of cell growth and proliferation — ribosome biogenesis, nucleotide and glycolytic metabolism, and cell-cycle entry via effectors such as cyclin-dependent kinase 1 (CDK1). The protein is short-lived and tightly regulated post-translationally: phosphorylation at Ser62 generally stabilizes MYC and enables subsequent phosphorylation at Thr58 by glycogen synthase kinase 3β (GSK-3β); dephosphorylation of Ser62 allows the Thr58 phosphodegron to promote FBW7-mediated ubiquitination and proteasomal degradation, so that its abundance normally tracks mitogenic signaling rather than persisting.
In malignancy this control is lost through gene amplification, chromosomal translocation, protein stabilization, or sustained upstream signaling from pathways such as MAPK, Phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (PKB), Wnt/β-catenin, NF-κB, and CD44/JAK2/STAT3. Elevated MYC is documented across leukemias, colorectal cancer, hepatocellular carcinoma, nasopharyngeal carcinoma, tongue and other head-and-neck squamous cell carcinomas, and lung adenocarcinoma, frequently alongside lesions in KRAS, BRAF, or CDH1 and with downstream effects on apoptotic regulators such as B-cell lymphoma 2 (Bcl-2). MYC can also repress a subset of targets — for example, it restrains tumor-associated calcium signal transducer 2 (TACSTD2/TROP2), so that MAPK-pathway inhibition by EGFR tyrosine kinase inhibitors like osimertinib lowers MYC and derepresses TROP2 in drug-tolerant persister cells, a dependency that TROP2-directed antibody–drug conjugates can exploit. Because its largely intrinsically disordered surface offers few conventional binding pockets, MYC has long been regarded as difficult to drug directly, and most therapeutic effort targets it indirectly — through upstream kinases and signaling nodes, transcriptional cofactor and super-enhancer dependencies, or regulators of MYC protein stability. Its influence extends beyond classical oncology, with MYC-linked transcriptional and apoptotic programs implicated in tissue injury settings such as spinal cord injury and ischemia-reperfusion-driven acute kidney injury.
Where the papers sit
26 papers from the last 6 months study MYC proto-oncogene (MYC) directly · updated from PubMed 12 Oct 2026
Study type 0 clinical trials · 2 observational · 2 human data · 16 preclinical · 6 unclassified
Themes 4 themes · 1 paradigm shift · 1 new direction
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MYC-Targeted Cancer Therapy
MYC-driven cancers are being approached through direct depletion of c-MYC or its regulatory machinery rather than transcriptional inhibition alone. RNA degraders, intracellular antibodies, BRD4 PROTACs, and RUVBL1/2 or AURKB inhibitors support this strategy across tumor types. Combination designs add radiosensitization, metabolic disruption, or immune reprogramming. Drug-tolerant persister cells and EGFR inhibitor resistance remain important barriers, motivating TROP2-directed approaches and molecular profiling.
13 papers · 50%
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Lymphoma Immune Biology
Lymphoma research is linking molecular subtype, immune evasion, and therapeutic response. In T-cell lymphoma, alantolactone lowers CD47 through PI3K/AKT and ERK signaling, potentially restoring macrophage phagocytosis. Proteogenomic classification of diffuse large B-cell lymphoma and CRISPR screens aim to identify tissue-specific oncogene dependencies. Histiocytic sarcoma studies add evidence that follicular lymphoma transdifferentiation and BRAF/MEK signaling can create actionable disease states.
4 papers · 15.4%
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Others — Cancer Progression and Biomarkers
MYC expression is being assessed as a classification and prognostic feature in neuroendocrine tumors, including Merkel cell carcinoma and large cell neuroendocrine carcinoma. Other studies examine patient-derived squamous carcinoma models and mechanisms of sunitinib resistance involving USP15, c-Myc, and cuproptosis. Psychological stress and bile-acid reprogramming connect signaling changes to hepatocellular carcinoma progression. A spinal-cord-injury study instead applies Myc/NF-κB biology to tissue recovery, leaving no single research direction.
5 papers · 19.2%
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Others — Cancer and Tissue Injury
Acute myeloid leukemia work targets metabolic reprogramming, ANP32B/C-MYC regulation, and immune clearance with anti-PD-1 or CAR-T approaches. Raloxifene and MO-IPS represent pharmacologic routes to suppress leukemia growth. A separate transplantation study uses a four-gene signature for acute kidney injury rather than a cancer mechanism. The cluster therefore has no unified biological or therapeutic trajectory.
4 papers · 15.4%
MYC suppression can enhance cancer therapy by reprogramming tumor metabolism and antitumor immunity, not only by directly killing MYC-dependent tumor cells
In acute myeloid leukemia treated with the MYC-PRMT inhibitor MO-IPS, and in postoperative residual tumors treated with a JQ1-containing CAR-T-supporting hydrogel, MYC inhibition produced therapeutic effects through metabolic and immune remodeling: reduced tumor glycolysis redirected nutrients and improved immune-cell function, while low-dose MO-IPS enhanced CD8⁺ T-cell infiltration and reduced regulatory T-cell accumulation despite minimizing direct cytotoxicity. These findings replace a strictly tumor-cell-intrinsic account of MYC targeting with one in which MYC suppression can function as an immunometabolic intervention that makes immunotherapy effective 42307804Jun 42105866May.
MYC acts as a transcriptional repressor in EGFR-inhibitor-tolerant lung cancer cells, where its loss induces a therapeutic TROP2 vulnerability
In EGFR-mutant non-small-cell lung cancer exposed to EGFR tyrosine kinase inhibitors, c-Myc was found to repress TROP2 transcription; MAPK inhibition lowered c-Myc, thereby increasing TROP2 during drug-tolerant persister-cell formation. This assigns MYC a role opposite to the usual oncogenic transcriptional-activation frame in the set and makes MYC loss, rather than MYC activity, part of the mechanism creating a targetable persister state 42314664Jun.
Papers
The 26 papers from the last 6 months that study MYC proto-oncogene (MYC) directly, newest first, by theme and by study type. Study types come from PubMed publication types and MeSH headings.
By theme
MYC-Targeted Cancer Therapy (13)
- Intracellular Delivery of Antibody-Based Therapeutics for Targeted Oncogenic c-Myc Degradation in Mammalian Cells and Mice. Angewandte Chemie (International ed. in English) · 20 Aug 2026 PMID 42622261
- Sequential Disruption of Tumor Camouflage and Metabolic Coercion by Cascade-Acting Nano-Proteolysis Targeting Chimera Engines to Reprogram the Immune Ecosystem. ACS nano · 11 Aug 2026 PMID 42579417
- A first-in-class RNA degrader reduces c-MYC expression and myeloma cell survival in preclinical models. Blood · 29 Jul 2026 PMID 42526890
- Investigating the mechanisms of malignant progression in colorectal cancer using weighted gene co-expression network analysis and machine learning. Journal of molecular histology · 18 Jul 2026 PMID 42470494
- PROTAC-based nanoassemblies targeting BRD4 for potentiate FLASH radiosensitization therapy. Materials today. Bio · 12 Jul 2026 PMID 42436803
- The Genomic Landscape of MYC-, MYCL-, and MYCN-Amplified Solid Tumors. Clinical cancer research : an official journal of the American Association for Cancer Research · 24 Jun 2026 PMID 42340371
- Large-scale and high-resolution mass spectrometry-based proteomics defines molecular subtypes of nasopharyngeal carcinoma for therapeutic targeting. Signal transduction and targeted therapy · 22 Jun 2026 PMID 42331772
- Targeting TROP2 in drug-tolerant persister cells delays EGFR tyrosine kinase inhibitor resistance in non-small-cell lung cancer. Cancer cell · 18 Jun 2026 PMID 42314664
- Dual Functional Potential of Poly(ADP-Ribose) Polymerase Inhibitor VIII: A Promising G-Quadruplex Stabilizer Targeting the Promoter of Oncogenes. Chemphyschem : a European journal of chemical physics and physical chemistry · 12 Jun 2026 PMID 42281329
- The NAT10/c-Myc positive feedback loop orchestrates tRNA ac4C modification and OTUB1-mediated protein stabilization to drive anaplastic thyroid carcinoma progression. Cellular & molecular biology letters · 12 Jun 2026 PMID 42277649
- Targeting AURKB Attenuates Tumor Growth in MYC-driven Lung Adenocarcinoma. Anticancer research · 27 May 2026 PMID 42203345
- Integrated LC-HRMS/MS-based metabolomics and in vitro and in vivo bioassays for comparative evaluation of two ethnomedicinal Paris species and their official counterparts. Journal of pharmaceutical and biomedical analysis · 24 Apr 2026 PMID 42030706
- Rapid Optimization Enabled by Single-Molecule Tracking: Discovery of a Potent RUVBL1/2 Inhibitor to Evaluate the Targeting of MYC-Driven Cancers. Journal of medicinal chemistry · 22 Apr 2026 PMID 42017951
Lymphoma Immune Biology (4)
- Alantolactone inhibits T-cell lymphoma progression by suppressing CD47 expression via the PI3K/AKT and ERK signaling pathways. Apoptosis : an international journal on programmed cell death · 23 Aug 2026 PMID 42634031
- Secondary BRAF-mutated histiocytic/dendritic cell sarcoma transdifferentiated from follicular lymphoma with prolonged response to BRAF/MEK inhibition and subsequent evolution to high-grade B-cell lymphoma. Journal of clinical pathology · 9 Jun 2026 PMID 42264920
- Pathogenesis of diffuse large B cell lymphoma proteogenotypes. Cancer cell · 4 Jun 2026 PMID 42242231
- An autochthonous CRISPR activation screening platform for characterizing tissue-specific oncogene selection. Cell reports. Medicine · 18 Apr 2026 PMID 41999750
Others — Cancer Progression and Biomarkers (5)
- Divergent c-MYC Expression Patterns in NET and NEC: Insights from a Multicentre Cohort of 1380 Neuroendocrine Neoplasms. Endocrine pathology · 12 Sept 2026 PMID 42730951
- Betulinic Acid Promotes Motor Function Recovery After Spinal Cord Injury by Inhibiting Apoptosis Through Myc/NF-κB Signaling Pathway. Neurochemical research · 20 Jul 2026 PMID 42477269
- Psychological Stress Associated Bile Acid Reprogramming Promotes Hepatocellular Carcinoma Progression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 11 Jul 2026 PMID 42435771
- Novel patient-derived tongue squamous cell carcinoma cell lines from non-smokers: 3D and in vivo models for drug response studies. Medical oncology (Northwood, London, England) · 29 Jun 2026 PMID 42371352
- USP15 stabilizes c-Myc to drive sunitinib resistance by suppressing cuproptosis in clear cell renal cell carcinoma. Cell reports · 29 Apr 2026 PMID 42054210
Others — Cancer and Tissue Injury (4)
- Raloxifene inhibits the proliferation of pediatric acute myeloid leukemia by targeting the ANP32B gene and regulating C-MYC expression. Hematology (Amsterdam, Netherlands) · 29 Jun 2026 PMID 42372253
- A four-gene signature for diagnosis of acute kidney injury following kidney transplantation. Renal failure · 18 Jun 2026 PMID 42315974
- MO-IPS suppresses acute myeloid leukemia through metabolic reprogramming and synergizes with anti-PD-1 immunotherapy. Functional & integrative genomics · 17 Jun 2026 PMID 42307804
- Dual regulation of metabolism and immune contact by a self-reinforcing hydrogel enhances CAR-T-mediated residual tumor clearance and surveillance. Journal of controlled release : official journal of the Controlled Release Society · 9 May 2026 PMID 42105866
By study type
Observational studies and case reports (2)
- Divergent c-MYC Expression Patterns in NET and NEC: Insights from a Multicentre Cohort of 1380 Neuroendocrine Neoplasms. Endocrine pathology · 12 Sept 2026 PMID 42730951
- Secondary BRAF-mutated histiocytic/dendritic cell sarcoma transdifferentiated from follicular lymphoma with prolonged response to BRAF/MEK inhibition and subsequent evolution to high-grade B-cell lymphoma. Journal of clinical pathology · 9 Jun 2026 PMID 42264920
Human data, design not indexed (2)
- The Genomic Landscape of MYC-, MYCL-, and MYCN-Amplified Solid Tumors. Clinical cancer research : an official journal of the American Association for Cancer Research · 24 Jun 2026 PMID 42340371
- Dual Functional Potential of Poly(ADP-Ribose) Polymerase Inhibitor VIII: A Promising G-Quadruplex Stabilizer Targeting the Promoter of Oncogenes. Chemphyschem : a European journal of chemical physics and physical chemistry · 12 Jun 2026 PMID 42281329
Preclinical: animal, cell and lab studies (16)
- Alantolactone inhibits T-cell lymphoma progression by suppressing CD47 expression via the PI3K/AKT and ERK signaling pathways. Apoptosis : an international journal on programmed cell death · 23 Aug 2026 PMID 42634031
- Intracellular Delivery of Antibody-Based Therapeutics for Targeted Oncogenic c-Myc Degradation in Mammalian Cells and Mice. Angewandte Chemie (International ed. in English) · 20 Aug 2026 PMID 42622261
- Sequential Disruption of Tumor Camouflage and Metabolic Coercion by Cascade-Acting Nano-Proteolysis Targeting Chimera Engines to Reprogram the Immune Ecosystem. ACS nano · 11 Aug 2026 PMID 42579417
- Betulinic Acid Promotes Motor Function Recovery After Spinal Cord Injury by Inhibiting Apoptosis Through Myc/NF-κB Signaling Pathway. Neurochemical research · 20 Jul 2026 PMID 42477269
- Investigating the mechanisms of malignant progression in colorectal cancer using weighted gene co-expression network analysis and machine learning. Journal of molecular histology · 18 Jul 2026 PMID 42470494
- Raloxifene inhibits the proliferation of pediatric acute myeloid leukemia by targeting the ANP32B gene and regulating C-MYC expression. Hematology (Amsterdam, Netherlands) · 29 Jun 2026 PMID 42372253
- Novel patient-derived tongue squamous cell carcinoma cell lines from non-smokers: 3D and in vivo models for drug response studies. Medical oncology (Northwood, London, England) · 29 Jun 2026 PMID 42371352
- A four-gene signature for diagnosis of acute kidney injury following kidney transplantation. Renal failure · 18 Jun 2026 PMID 42315974
- Targeting TROP2 in drug-tolerant persister cells delays EGFR tyrosine kinase inhibitor resistance in non-small-cell lung cancer. Cancer cell · 18 Jun 2026 PMID 42314664
- MO-IPS suppresses acute myeloid leukemia through metabolic reprogramming and synergizes with anti-PD-1 immunotherapy. Functional & integrative genomics · 17 Jun 2026 PMID 42307804
- Targeting AURKB Attenuates Tumor Growth in MYC-driven Lung Adenocarcinoma. Anticancer research · 27 May 2026 PMID 42203345
- Dual regulation of metabolism and immune contact by a self-reinforcing hydrogel enhances CAR-T-mediated residual tumor clearance and surveillance. Journal of controlled release : official journal of the Controlled Release Society · 9 May 2026 PMID 42105866
- USP15 stabilizes c-Myc to drive sunitinib resistance by suppressing cuproptosis in clear cell renal cell carcinoma. Cell reports · 29 Apr 2026 PMID 42054210
- Integrated LC-HRMS/MS-based metabolomics and in vitro and in vivo bioassays for comparative evaluation of two ethnomedicinal Paris species and their official counterparts. Journal of pharmaceutical and biomedical analysis · 24 Apr 2026 PMID 42030706
- Rapid Optimization Enabled by Single-Molecule Tracking: Discovery of a Potent RUVBL1/2 Inhibitor to Evaluate the Targeting of MYC-Driven Cancers. Journal of medicinal chemistry · 22 Apr 2026 PMID 42017951
- An autochthonous CRISPR activation screening platform for characterizing tissue-specific oncogene selection. Cell reports. Medicine · 18 Apr 2026 PMID 41999750
Unclassified: not yet indexed with MeSH (6)
- A first-in-class RNA degrader reduces c-MYC expression and myeloma cell survival in preclinical models. Blood · 29 Jul 2026 PMID 42526890
- PROTAC-based nanoassemblies targeting BRD4 for potentiate FLASH radiosensitization therapy. Materials today. Bio · 12 Jul 2026 PMID 42436803
- Psychological Stress Associated Bile Acid Reprogramming Promotes Hepatocellular Carcinoma Progression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 11 Jul 2026 PMID 42435771
- Large-scale and high-resolution mass spectrometry-based proteomics defines molecular subtypes of nasopharyngeal carcinoma for therapeutic targeting. Signal transduction and targeted therapy · 22 Jun 2026 PMID 42331772
- The NAT10/c-Myc positive feedback loop orchestrates tRNA ac4C modification and OTUB1-mediated protein stabilization to drive anaplastic thyroid carcinoma progression. Cellular & molecular biology letters · 12 Jun 2026 PMID 42277649
- Pathogenesis of diffuse large B cell lymphoma proteogenotypes. Cancer cell · 4 Jun 2026 PMID 42242231
Written from 26 PubMed abstracts, each one listed by PMID above. Published: 2026-06-16. Last written: 2026-09-14 by GPT. Corrections: 2026-09-26 by GPT. Reviewed by a human editor on 2026-07-24. Drafted by language models from published abstracts; not medical advice.