ArticleMolecular cancer2024
A novel pan-PI3K inhibitor KTC1101 synergizes with anti-PD-1 therapy by targeting tumor suppression and immune activation.
Article in Molecular cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Article
- A longitudinal, multi-omic atlas reveals the emergence of a spatially organized immunosuppressive ecosystem in resistant melanoma.Cell reports. Medicine · 2026Article
- Targeted Therapies in Infantile Hemangiomas and Vascular Malformations: From β-Blockers to PI3K/AKT/mTOR Inhibitors.Journal of cellular and molecular medicine · 2026Review
- Decoding Immunotherapy Response in Colorectal Cancer: Translational Insights Beyond MSI.Cancers · 2026Review
- From intracellular drivers to immune modulators: emerging paradigms in oncogenic pathway-directed immunotherapy optimization.Cell communication and signaling : CCS · 2025Review
- Spatiotemporal Heterogeneity of Tumor Glucose Metabolism Reprogramming: From Single-Cell Mechanisms to Precision Interventions.International journal of molecular sciences · 2025Review
- PI3K Signaling Pathway Inhibitor Affects Myeloma Cells in a Culture-Dependent Manner.Advanced pharmaceutical bulletin · 2025Article
- Immuno-Oncology at the Crossroads: Confronting Challenges in the Quest for Effective Cancer Therapies.International journal of molecular sciences · 2025Review
- Antitumor effect of BC12-3 on multiple myeloma via proteasome inhibition.Medical oncology (Northwood, London, England) · 2025Article
- Nanomedicine-driven tumor glucose metabolic reprogramming for enhanced cancer immunotherapy.Acta pharmaceutica Sinica. B · 2025Review
- Tumor-associated macrophages remodel the suppressive tumor immune microenvironment and targeted therapy for immunotherapy.Journal of experimental & clinical cancer research : CR · 2025Review
- Review
- Oncogenic Signalling Pathways in Cancer Immunotherapy: Leader or Follower in This Delicate Dance?International journal of molecular sciences · 2025Review
- Reconstructing the hepatocellular carcinoma microenvironment: the current status and challenges of 3D culture technology.Discover oncology · 2025Review
- Exploring the molecular mechanism of Tripterygium Wilfordii Hook F in treating systemic lupus erythematosus via network pharmacology and molecular docking.Clinical rheumatology · 2025Article
- Comprehensive immunophenotyping reveals distinct tumor microenvironment alterations in anti-PD-1 sensitive and resistant syngeneic mouse model.Scientific reports · 2025Article
- Multiple mechanisms and applications of tertiary lymphoid structures and immune checkpoint blockade.Journal of experimental & clinical cancer research : CR · 2025Review
- In Silico Discovery of a Novel PI3Kδ Inhibitor Incorporating 3,5,7-Trihydroxychroman-4-one Targeting Diffuse Large B-Cell Lymphoma.International journal of molecular sciences · 2024Article
- Advances in Melanoma: From Genetic Insights to Therapeutic Innovations.Biomedicines · 2024Review
- Beyond Anti-PD-1/PD-L1: Improving Immune Checkpoint Inhibitor Responses in Triple-Negative Breast Cancer.Cancers · 2024Review
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Authors and funding
18 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundPhosphoinositide 3-kinases (PI3Ks) are critical regulators of diverse cellular functions and have emerged as promising targets in cancer therapy. Despite significant progress, existing PI3K inhibitors encounter various challenges such as suboptimal bioavailability, potential off-target effects, restricted therapeutic indices, and cancer-acquired resistance. Hence, novel inhibitors that overcome some of these challenges are needed. Here, we describe the characterization of KTC1101, a novel pan-PI3K inhibitor that simultaneously targets tumor cell proliferation and the tumor microenvironment. Our studies demonstrate that KTC1101 significantly increases the anti-PD-1 efficacy in multiple pre-clinical mouse models.
methodsKTC1101 was synthesized and characterized employing chemical synthesis, molecular modeling, Nuclear Magnetic Resonance (NMR), and mass spectrometry. Its target specificity was confirmed through the kinase assay, JFCR39 COMPARE analysis, and RNA-Seq analysis. Metabolic stability was verified via liver microsome and plasma assays, pharmacokinetics determined by LC-MS/MS, and safety profile established through acute toxicity assays to determine the LD50. The antiproliferative effects of KTC1101 were evaluated in a panel of cancer cell lines and further validated in diverse BALB/c nude mouse xenograft, NSG mouse xenograft and syngeneic mouse models. The KTC1101 treatment effect on the immune response was assessed through comprehensive RNA-Seq, flow cytometry, and immunohistochemistry, with molecular pathways investigated via Western blot, ELISA, and qRT-PCR.
resultsKTC1101 demonstrated strong inhibition of cancer cell growth in vitro and significantly impeded tumor progression in vivo. It effectively modulated the Tumor Microenvironment (TME), characterized by increased infiltration of CD8
conclusionKTC1101's dual mechanism of action-directly inhibiting tumor cell growth and dynamically enhancing the immune response- represents a significant advancement in cancer treatment strategies. These findings support incorporating KTC1101 into future oncologic regimens to improve the efficacy of immunotherapy combinations.
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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.