ArticleMolecular cancer2021
Novel induction of CD40 expression by tumor cells with RAS/RAF/PI3K pathway inhibition augments response to checkpoint blockade.
Article in Molecular cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01205815 (Storage and Research Use of Human Bio-specimens From Melanoma Patients and Clinical Testing for Assignment of Treatment), which is not on this map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Storage and Research Use of Human Bio-specimens From Melanoma Patients and Clinical Testing for Assignment of Treatment
Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- CD40 Agonist Therapy in Melanoma: Translating Preclinical Promise Into Clinical Practice.Pigment cell & melanoma research · 2026Review
- RAS/MEK/PI3K pathway inhibition augments response to CD40 agonism by targeting CD11bNature communications · 2026Article
- Resistance mechanisms and reversal strategies of PD-1/PD-L1 inhibitors in melanoma.Frontiers in pharmacology · 2026Review
- Gas plasma-induced bacterial PAMP release promotes skin cancer cell death.Cell death & disease · 2025Article
- CETSA-MS unveils novel targets engaged by rigosertib to promote anti-tumor activity and inflammatory responses.iScience · 2025Article
- Exosomal CD40, CD25, and Serum CA19-9 as Combinatory Novel Liquid Biopsy Biomarker for the Diagnosis and Prognosis of Patients with Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2025Article
- CD40 ligation-induced ERK activation leads to enhanced radiosensitivity in cervical carcinoma cells via promoting autophagy.Acta biochimica et biophysica Sinica · 2024Article
- A High-Throughput Immune-Oncology Screen Identifies Immunostimulatory Properties of Cytotoxic Chemotherapy Agents in TNBC.Cancers · 2024Article
- Innate immune cells in tumor microenvironment: A new frontier in cancer immunotherapy.iScience · 2024Review
- Strategies to enhance the therapeutic efficacy of anti-PD-1 antibody, anti-PD-L1 antibody and anti-CTLA-4 antibody in cancer therapy.Journal of translational medicine · 2024Review
- Review
- CD40 stimulation via CD40 ligand enhances adenovirus-mediated tumour immunogenicity including 'find-me', 'eat-me', and 'kill-me' signalling.Journal of cellular and molecular medicine · 2024Article
- Harnessing the potential of CD40 agonism in cancer therapy.Cytokine & growth factor reviews · 2024Review
- Current and future therapeutic strategies for high-grade gliomas leveraging the interplay between epigenetic regulators and kinase signaling networks.Journal of experimental & clinical cancer research : CR · 2024Review
- Article
- Effects of Electrochemotherapy on Immunologically Important Modifications in Tumor Cells.Vaccines · 2023Article
- Lights and Shadows on the Cancer Multi-Target Inhibitor Rigosertib (ON-01910.Na).Pharmaceutics · 2023Review
- Spatial characterization and quantification of CD40 expression across cancer types.BMC cancer · 2023Article
- Newly identified form of phenotypic plasticity of cancer: immunogenic mimicry.Cancer metastasis reviews · 2023Review
- CD40/CD40L expression and its prognostic value in cervical cancer.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundWhile immune checkpoint blockade (ICB) is the current first-line treatment for metastatic melanoma, it is effective for ~ 52% of patients and has dangerous side effects. The objective here was to identify the feasibility and mechanism of RAS/RAF/PI3K pathway inhibition in melanoma to sensitize tumors to ICB therapy.
methodsRigosertib (RGS) is a non-ATP-competitive small molecule RAS mimetic. RGS monotherapy or in combination therapy with ICB were investigated using immunocompetent mouse models of BRAF
resultsRGS treatment (300 mg/kg) was well tolerated in mice and resulted in ~ 50% inhibition of tumor growth as monotherapy and ~ 70% inhibition in combination with αPD1 + αCTLA4. RGS-induced tumor growth inhibition depends on CD40 upregulation in melanoma cells followed by immunogenic cell death, leading to enriched dendritic cells and activated T cells in the tumor microenvironment. The RGS-initiated tumor suppression was partially reversed by either knockdown of CD40 expression in melanoma cells or depletion of CD8
conclusionsOur data support the therapeutic use of RGS + αPD1 + αCTLA4 in RAS/RAF/PI3K pathway-activated melanomas and point to the need for clinical trials of RGS + ICB for melanoma patients who do not respond to ICB alone.
trial registrationNCT01205815 (Sept 17, 2010).
Indexed as
Identifiers
What OpenQuestion holds
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.