ArticleEmerging topics in life sciences2017
The MAPK hypothesis: immune-regulatory effects of MAPK-pathway genetic dysregulations and implications for breast cancer immunotherapy.
Article in Emerging topics in life sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
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- Gelsolin (GSN) as a key regulator in estrogen receptor-positive breast cancer: implications for prognosis, chemotherapy sensitivity, and immune infiltration.Discover oncology · 2025Article
- A patient stratification signature mirrors the immunogenic potential of high grade serous ovarian cancers.Journal of translational medicine · 2024Article
- MAP3K1 mutations confer tumor immune heterogeneity in hormone receptor-positive HER2-negative breast cancer.The Journal of clinical investigation · 2024Article
- Intermittent MEK Inhibition with GITR Costimulation Rescues T-cell Function for Increased Efficacy with CTLA-4 Blockade in Solid Tumor Models.Cancer immunology research · 2024Article
- Genomic and molecular alterations associated with primary resistance to immune checkpoint inhibitors.Cancer immunology, immunotherapy : CII · 2024Review
- Biomarkers of immunotherapy in glioblastoma.Neuro-oncology practice · 2024Review
- Comparative analysis identifies genetic and molecular factors associated with prognostic clusters of PANoptosis in glioma, kidney and melanoma cancer.Scientific reports · 2023Article
- Novel, clinically relevant genomic patterns identified by comprehensive genomic profiling in ATRX-deficient IDH-wildtype adult high-grade gliomas.Scientific reports · 2023Article
- A pathway-based mutation signature to predict the clinical outcomes and response to CTLA-4 inhibitors in melanoma.Computational and structural biotechnology journal · 2023Article
- Repurposing of Commercially Existing Molecular Target Therapies to Boost the Clinical Efficacy of Immune Checkpoint Blockade.Cancers · 2022Review
- Immune Checkpoint Inhibitors and RAS-ERK Pathway-Targeted Drugs as Combined Therapy for the Treatment of Melanoma.Biomolecules · 2022Review
- Review
- Current WHO Guidelines and the Critical Role of Genetic Parameters in the Classification of Glioma: Opportunities for Immunotherapy.Current treatment options in oncology · 2022Review
- Systematic Analysis of Neurotransmitter Receptors in Human Breast Cancer Reveals a Strong Association With Outcome and Uncovers HTR6 as a Survival-Associated Gene Potentially Regulating the Immune Microenvironment.Frontiers in immunology · 2022Article
- SLFN11 captures cancer-immunity interactions associated with platinum sensitivity in high-grade serous ovarian cancer.JCI insight · 2021Article
- ICN: Extracting interconnected communities in gene Co-expression networks.Bioinformatics (Oxford, England) · 2021Article
- Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
With the advent of checkpoint inhibition, immunotherapy has revolutionized the clinical management of several cancers, but has demonstrated limited efficacy in mammary carcinoma. Transcriptomic profiling of cancer samples defined distinct immunophenotypic categories characterized by different prognostic and predictive connotations. In breast cancer, genomic alterations leading to the dysregulation of mitogen-activated protein kinase (MAPK) pathways have been linked to an immune-silent phenotype associated with poor outcome and treatment resistance. These aberrations include mutations of MAP3K1 and MAP2K4, amplification of KRAS, BRAF, and RAF1, and truncations of NF1. Anticancer therapies targeting MAPK signaling by BRAF and MEK inhibitors have demonstrated clear immunologic effects. These off-target properties could be exploited to convert the immune-silent tumor phenotype into an immune-active one. Preclinical evidence supports that MAPK-pathway inhibition can dramatically increase the efficacy of immunotherapy. In this review, we provide a detailed overview of the immunomodulatory impact of MAPK-pathway blockade through BRAF and MEK inhibitions. While BRAF inhibition might be relevant in melanoma only, MEK inhibition is potentially applicable to a wide range of tumors. Context-dependent similarities and differences of MAPK modulation will be dissected, in light of the complexity of the MAPK pathways. Therapeutic strategies combining the favorable effects of MAPK-oriented interventions on the tumor microenvironment while maintaining T-cell function will be presented. Finally, we will discuss recent studies highlighting the rationale for the implementation of MAPK-interference approaches in combination with checkpoint inhibitors and immune agonists in breast cancer.
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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.