MUC1 is a potential target to overcome trastuzumab resistance in breast cancer therapy

Although resistance is its major obstacle in cancer therapy, trastuzumab is the most successful agent in treating epidermal growth factor receptor 2 positive (HER2 +) breast cancer (BC). Some patients show resistance to trastuzumab, and scientists want to circumvent this problem. This review elaborately discusses possible resistance mechanisms to trastuzumab and introduces mucin 1 (MUC1) as a potential target efficient for overcoming such resistance. MUC1 belongs to the mucin family, playing the oncogenic/mitogenic roles in cancer cells and interacting with several other oncogenic receptors and pathways, such as HER2, β-catenin, NF-κB, and estrogen receptor (ERα). Besides, it has been established that MUC1- Cytoplasmic Domain (MUC1-CD) accelerates the development of resistance to trastuzumab and that silencing MUC1-C proto-oncogene is associated with increased sensitivity of HER2 + cells to trastuzumab-induced growth inhibitors. We mention why targeting MUC1 can be useful in overcoming trastuzumab resistance in cancer therapy.

• Publication year

  2022

• Venue

  Cancer Cell International

• Publication date

  2022-03-05

• Fields of study

  Medicine

• Identifiers
  DOI 10.1186/s12935-022-02523-zPMID 35248049PMCID 8897942
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Development, Characterization, and In Vivo Evaluation of a Novel Aptamer (Anti-MUC1/Y) for Breast Cancer Therapy

  2021cited by this paper
• MEK inhibitors for the treatment of non-small cell lung cancer

  2021cited by this paper
• A phase II randomised study of preoperative trastuzumab alone or combined with everolimus in patients with early HER2-positive breast cancer and predictive biomarkers (RADHER trial).

  2021cited by this paper
• The Novel Oral mTORC1/2 Inhibitor TAK-228 Reverses Trastuzumab Resistance in HER2-Positive Breast Cancer Models

  2021cited by this paper
• Phase 1 study of M2698, a p70S6K/AKT dual inhibitor, in patients with advanced cancer

  2021cited by this paper
• Crosstalk between MUC1 and VEGF in angiogenesis and metastasis: a review highlighting roles of the MUC1 with an emphasis on metastatic and angiogenic signaling

  2021cited by this paper
• Synthesis, conformational analysis and in vivo assays of an anti-cancer vaccine that features an unnatural antigen based on an sp2-iminosugar fragment

  2020cited by this paper
• Signal Transduction Pathways in Breast Cancer: The Important Role of PI3K/Akt/mTOR

  2020cited by this paper
• Role of STAT3 signaling pathway in breast cancer

  2020influential reference
• Acquired resistance to trastuzumab/pertuzumab or to T‐DM1 in vivo can be overcome by HER2 kinase inhibition with TAS0728

  2020cited by this paper
• An updated evaluation of serum sHER2, CA15.3, and CEA levels as biomarkers for the response of patients with metastatic breast cancer to trastuzumab-based therapies

  2020cited by this paper
• RNA sequencing reveals an additional Crz1-binding motif in promoters of its target genes in the human fungal pathogen Candida albicans

  2020cited by this paper
• Novel Antibodies Targeting MUC1-C Showed Anti-Metastasis and Growth-Inhibitory Effects on Human Breast Cancer Cells

  2020influential reference
• Dual-targeted therapy in HER2-positive breast cancer cells with the combination of carbon dots/HER3 siRNA and trastuzumab

  2020cited by this paper
• CAR T Cells Targeting the Tumor MUC1 Glycoprotein Reduce Triple-Negative Breast Cancer Growth

  2019cited by this paper
• Diagnostic Leukapheresis Enables Reliable Transcriptomic Profiling of Single Circulating Tumor Cells to Characterize Inter-Cellular Heterogeneity in Terms of Endocrine Resistance

  2019cited by this paper
• Indomethacin enhances anti-tumor efficacy of a MUC1 peptide vaccine against breast cancer in MUC1 transgenic mice

  2019influential reference
• Monoclonal anti-MUC1 antibody with novel octahydropyrazino[2,1-a:5,4-a′]diisoquinoline derivative as a potential multi-targeted strategy in MCF-7 breast cancer cells

  2019cited by this paper
• Anti-KL-6/MUC1 monoclonal antibody reverses resistance to trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity by capping MUC1.

  2019influential reference
• Targeting of the HER2/HER3 signaling axis overcomes ligand‐mediated resistance to trastuzumab in HER2‐positive breast cancer

  2019cited by this paper
• Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b-2 trial.

  2019cited by this paper
• MK-2206 and Standard Neoadjuvant Chemotherapy Improves Response in Patients With Human Epidermal Growth Factor Receptor 2-Positive and/or Hormone Receptor-Negative Breast Cancers in the I-SPY 2 Trial.

  2019influential reference
• WEE1 Inhibitor, AZD1775, Overcomes Trastuzumab Resistance by Targeting Cancer Stem-like Properties in HER2-positive Breast Cancer.

  2019cited by this paper
• Monoclonal antibody‐based therapeutics, targeting the epidermal growth factor receptor family: from herceptin to Pan HER

  2018cited by this paper
• Overexpression of MUC1 predicts poor prognosis in patients with breast cancer

  2018influential reference
• The Multifaceted Role of STAT3 in Mammary Gland Involution and Breast Cancer

  2018influential reference
• Combination Immunotherapy of MUC1 mRNA Nano-vaccine and CTLA-4 Blockade Effectively Inhibits Growth of Triple Negative Breast Cancer.

  2018cited by this paper
• Targeting MUC1-C suppresses BCL2A1 in triple-negative breast cancer

  2018influential reference
• Dual inhibition of STAT1 and STAT3 activation downregulates expression of PD-L1 in human breast cancer cells

  2018cited by this paper
• Publisher's Note

  2018cited by this paper
• MUC1-C Induces PD-L1 and Immune Evasion in Triple-Negative Breast Cancer.

  2018influential reference
• Crosstalk between MUC1 oncoprotein and ER, PR, and HER2 receptors in breast cancer cells

  2018cited by this paper
• A phase I trial of ganetespib in combination with paclitaxel and trastuzumab in patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer

  2017cited by this paper
• Elevation of serum CEA and CA15-3 levels during antitumor therapy predicts poor therapeutic response in advanced breast cancer patients.

  2017cited by this paper
• MUC1 induces acquired chemoresistance by upregulating ABCB1 in EGFR-dependent manner

  2017cited by this paper
• Mechanism of anticancer action of novel berenil complex of platinum(II) combined with anti-MUC1 in MCF-7 breast cancer cells

  2017cited by this paper
• MUC1 induces tamoxifen resistance in estrogen receptor-positive breast cancer

  2017cited by this paper
• PIKHER2: A phase IB study evaluating buparlisib in combination with lapatinib in trastuzumab-resistant HER2-positive advanced breast cancer.

  2017influential reference
• Mucins and Wnt/β-catenin signaling in gastrointestinal cancers: an unholy nexus.

  2016cited by this paper
• Anti-MUC1 nano-aptamers for triple-negative breast cancer imaging by single-photon emission computed tomography in inducted animals: initial considerations

  2016cited by this paper
• Mucin 1-specific B cell immune responses and their impact on overall survival in breast cancer patients

  2016cited by this paper
• Functional interactions of the cystine/glutamate antiporter, CD44v and MUC1-C oncoprotein in triple-negative breast cancer cells

  2016cited by this paper
• MUC1-C Stabilizes MCL-1 in the Oxidative Stress Response of Triple-Negative Breast Cancer Cells to BCL-2 Inhibitors

  2016cited by this paper
• Characterization of the MUC1-C Cytoplasmic Domain as a Cancer Target

  2015cited by this paper
• Combating HER2-overexpressing breast cancer through induction of calreticulin exposure by Tras-Permut CrossMab

  2015cited by this paper
• Elevated Levels of Serum Tumor Markers CEA and CA15-3 Are Prognostic Parameters for Different Molecular Subtypes of Breast Cancer

  2015cited by this paper
• Mechanisms of action of therapeutic antibodies for cancer.

  2015cited by this paper
• Multifunctional receptor-targeting antibodies for cancer therapy.

  2015cited by this paper
• Sustained proliferation in cancer: Mechanisms and novel therapeutic targets.

  2015cited by this paper
• Constitutive phosphorylated STAT3-associated gene signature is predictive for trastuzumab resistance in primary HER2-positive breast cancer

  2015cited by this paper
• The Path to Cancer --Three Strikes and You're Out.

  2015cited by this paper
• Targeting the STAT3 signaling pathway in cancer: role of synthetic and natural inhibitors.

  2014cited by this paper
• A phase II open-label study of ganetespib, a novel heat shock protein 90 inhibitor for patients with metastatic breast cancer.

  2014cited by this paper
• MUC1 regulates cyclin D1 gene expression through p120 catenin and β-catenin

  2014cited by this paper
• Pertuzumab and its accelerated approval: evolving treatment paradigms and new challenges in the management of HER2-positive breast cancer.

  2014cited by this paper
• Aldehyde dehydrogenase and estrogen receptor define a hierarchy of cellular differentiation in the normal human mammary epithelium

  2014cited by this paper
• Signaling cross-talk in the resistance to HER family receptor targeted therapy

  2014cited by this paper
• The PI3K/mTOR dual inhibitor P7170 demonstrates potent activity against endocrine-sensitive and endocrine-resistant ER+ breast cancer

  2014cited by this paper
• Breast cancer immunotherapy: monoclonal antibodies and peptide-based vaccines

  2014cited by this paper
• P-REX1 creates a positive feedback loop to activate growth factor receptor, PI3K/AKT, and MEK/ERK signaling in breast cancer

  2014cited by this paper
• Trastuzumab emtansine: mechanisms of action and drug resistance

  2014cited by this paper
• Targeting the PI3K/AKT/mTOR pathway in estrogen receptor-positive breast cancer.

  2014cited by this paper
• Targeting the MUC1-C oncoprotein inhibits self-renewal capacity of breast cancer cells

  2014influential reference
• Feedback activation of STAT3 mediates trastuzumab resistance via upregulation of MUC1 and MUC4 expression

  2014cited by this paper
• Nestin positively regulates the Wnt/β-catenin pathway and the proliferation, survival and invasiveness of breast cancer stem cells

  2014cited by this paper
• PI3K and cancer: lessons, challenges and opportunities

  2014cited by this paper
• Strategies to overcome trastuzumab resistance in HER2-overexpressing breast cancers: focus on new data from clinical trials

  2014cited by this paper
• MUC1 drives epithelial-mesenchymal transition in renal carcinoma through Wnt/β-catenin pathway and interaction with SNAIL promoter.

  2014cited by this paper
• MUC1-C oncoprotein as a target in breast cancer: activation of signaling pathways and therapeutic approaches

  2013cited by this paper
• Effect of MUC1 siRNA on drug resistance of gastric cancer cells to trastuzumab.

  2013cited by this paper
• Evaluation of Mucin-1 protein and mRNA expression as prognostic and predictive markers after neoadjuvant chemotherapy for breast cancer.

  2013cited by this paper
• Novel targeted therapies to overcome trastuzumab resistance in HER2-overexpressing metastatic breast cancer.

  2013cited by this paper
• Oncogenic MUC1-C Promotes Tamoxifen Resistance in Human Breast Cancer

  2013cited by this paper
• An Investigation of the Effects of the Core Protein Telomerase Reverse Transcriptase on Wnt Signaling in Breast Cancer Cells

  2013cited by this paper
• TARGETING THE MUC1-C ONCOPROTEIN DOWNREGULATES HER2 ACTIVATION AND ABROGATES TRASTUZUMAB RESISTANCE IN BREAST CANCER CELLS

  2013influential reference
• MicroRNA-374a activates Wnt/β-catenin signaling to promote breast cancer metastasis.

  2013cited by this paper
• Role of STAT3 in Cancer Metastasis and Translational Advances

  2013cited by this paper
• Antibody Therapeutics in Cancer

  2013cited by this paper
• Molecular aspects of cancer cell resistance to chemotherapy.

  2013cited by this paper
• Inhibition of the MUC1-C oncoprotein is synergistic with cytotoxic agents in the treatment of breast cancer cells

  2013cited by this paper
• The role of tumour-associated MUC1 in epithelial ovarian cancer metastasis and progression

  2013influential reference
• MUC1-C Oncoprotein Activates ERK→C/EBPβ Signaling and Induction of Aldehyde Dehydrogenase 1A1 in Breast Cancer Cells*

  2013cited by this paper
• The MUC1-C Oncoprotein Binds to the BH3 Domain of the Pro-apoptotic BAX Protein and Blocks BAX Function*

  2012influential reference
• Crosstalk between NFkB and glucocorticoid signaling: a potential target of breast cancer therapy.

  2012cited by this paper
• Antitumor Activity of a Novel Bispecific Antibody That Targets the ErbB2/ErbB3 Oncogenic Unit and Inhibits Heregulin-Induced Activation of ErbB3

  2012cited by this paper
• Concomitant targeting of tumor cells and induction of T-cell response synergizes to effectively inhibit trastuzumab-resistant breast cancer.

  2012cited by this paper
• EGFR-Mediated Carcinoma Cell Metastasis Mediated by Integrin αvβ5 Depends on Activation of c-Src and Cleavage of MUC1

  2012cited by this paper
• Mechanisms of Resistance to Trastuzumab and Novel Therapeutic Strategies in HER2-Positive Breast Cancer

  2012cited by this paper
• Activation of an IL6 inflammatory loop mediates trastuzumab resistance in HER2+ breast cancer by expanding the cancer stem cell population.

  2012cited by this paper
• MUC1 Drives c-Met–Dependent Migration and Scattering

  2012cited by this paper
• Treatment of HER2-positive breast cancer: current status and future perspectives

  2012influential reference
• Therapeutic strategies and mechanisms of tumorigenesis of HER2-overexpressing breast cancer.

  2012cited by this paper
• The ERBB network: at last, cancer therapy meets systems biology

  2012influential reference
• Trastuzumab emtansine for HER2-positive advanced breast cancer.

  2012cited by this paper
• Therapeutic MUC1-Based Cancer Vaccine Expressed in Flagella-Efficacy in an Aggressive Model of Breast Cancer

  2012cited by this paper
• MUC1‐C oncoprotein confers androgen‐independent growth of human prostate cancer cells

  2012influential reference
• Randomized Phase II Trial of Letrozole plus Anti-MUC1 Antibody AS1402 in Hormone Receptor–Positive Locally Advanced or Metastatic Breast Cancer

  2011cited by this paper
• HSP90 Inhibition Is Effective in Breast Cancer: A Phase II Trial of Tanespimycin (17-AAG) Plus Trastuzumab in Patients with HER2-Positive Metastatic Breast Cancer Progressing on Trastuzumab

  2011cited by this paper
• Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with HER2-overexpressing metastatic breast cancer who progressed on trastuzumab-based therapy.

  2011cited by this paper
• A Pilot Study of MUC-1/CEA/TRICOM Poxviral-Based Vaccine in Patients with Metastatic Breast and Ovarian Cancer

  2011cited by this paper

• Association of Matricellular Protein, Growth Factor, and Transcription Factor with Molecular Subtypes of Breast Cancer: A Case Control Study

  2026cites this paper
• β-Hydroxybutyrate promotes chemoresistance and proliferation in breast cancer cells

  2025cites this paper
• Role of MYC inhibition in overcoming resistance to HER2-targeted therapies for breast cancer.

  2025cites this paper
• Mucin-1: a promising pan-cancer therapeutic target

  2025cites this paper
• Dual Approaches in Oncology: The Promise of siRNA and Chemotherapy Combinations in Cancer Therapies

  2025cites this paper
• MUC1 aptamer-functionalized chitosan nanoparticles: Targeted delivery platforms for synergistic cancer therapy and multidrug resistance overcoming.

  2025cites this paper
• Targeting WEE1 Kinase for Breast Cancer Therapeutics: An Update

  2025cites this paper
• CAR T-cell structure, manufacturing, applications, and challenges in the management of communityacquired diseases and disorders

  2025cites this paper
• E2F4 Promotes Malignant Behaviors of Prostate Cancer Through Activating MUC1 Expression Transcriptionally

  2025cites this paper
• Targeting Siglec–Sialylated MUC1 Immune Axis in Cancer

  2024cites this paper
• Inhibition of breast cancer cell growth and migration through siRNA-mediated modulation of circ_0009910/miR-145-5p/MUC1 axis

  2024cites this paper
• In Vitro MRS of Cells Treated with Trastuzumab at 1.5 Tesla

  2024cites this paper
• MUC1-EGFR crosstalk with IL-6 by activating NF-κB and MAPK pathways to regulate the stemness and paclitaxel-resistance of lung adenocarcinoma

  2024cites this paper
• MUC1-C: The Occam Razor of Osimertinib Resistance?

  2024cites this paper
• Bioinformatics and In Vitro Study Reveal ERα as The Potential Target Gene of Honokiol to Enhance Trastuzumab Sensitivity in HER2+ Trastuzumab-Resistant Breast Cancer Cells

  2024cites this paper
• Strategies for Enhancing Non-small Cell Lung Cancer Treatment: Integrating Chinese Herbal Medicines with Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors Therapy.

  2024cites this paper
• Targeting overexpressed surface proteins: A new strategy to manage the recalcitrant triple-negative breast cancer.

  2024cites this paper
• A mini-review-cancer energy reprogramming on drug resistance and immune response

  2024cites this paper
• Antibody-drug conjugates in oncology: insights into Current challenges

  2023cites this paper
• Understanding the mechanistic pathways and clinical aspects associated with protein and gene based biomarkers in breast cancer.

  2023cites this paper
• Anti-MUC1 nanobody can synergize the Tamoxifen and Herceptin effects on breast cancer cells by inducing ER, PR and HER2 overexpression.

  2023cites this paper
• Lyophilization Based Isolation of Exosomes

  2023cites this paper
• Identification of Candidate Therapeutic Genes for More Precise Treatment of Esophageal Squamous Cell Carcinoma and Adenocarcinoma

  2022cites this paper
• ALKBH family members as novel biomarkers and prognostic factors in human breast cancer

  2022cites this paper
• The multifaceted role of MUC1 in tumor therapy resistance

  2022cites this paper
• Expression of MUC1 in different tumours and its clinical significance (Review)

  2022cites this paper
• The Nrf2 inhibitor brusatol synergistically enhances the cytotoxic effect of lapatinib in HER2-positive cancers

  2022cites this paper