Turalio (pexidartinib) / Daiichi Sankyo - LARVOL DELTA

EXPLORING INDUCIBLE NITRIC OXIDE SYNTHASE (INOS) AS A PET IMAGING TARGET OF OXIDATIVE STRESS IN PARKINSON'S DISEASE (PD) (ADPD 2026) - "Building on evidence that elevated inducible nitric oxide synthase (iNOS) accompanies microglial activation in PD, we evaluated iNOS as a positron emission tomography (PET) target to track oxidative stress ex vivo. We analyzed postmortem human brain tissues (Control n=4; PD n=7; PDD n=5), alongside three α-synuclein seeding mouse models (WT-hPFF, n=4; ampLBD—Thy1:SNCA/Snca–/– n=5; hPFF—Thy1:SNCA/Snca–/–, n=3) and a microglial depletion mouse model (WT-PLX3397; n=3)... Our findings indicate that iNOS is predominantly microglial and more tightly linked to PD pathology than TSPO, supporting iNOS as a promising PET target for monitoring microglia-mediated oxidative stress in PD. Several iNOS radioligands candidates have been identified, and in vitro binding and selectivity assays are underway."

Oxidative stress • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • SNCA

MICROGLIAL INFLUENCE ON AMYLOID –TAU CROSSTALK (ADPD 2026) - "We aimed to systematically assess microglia depletion at distinct disease stages across different AD mouse models. Microglia were depleted using PLX3397 (CSF1R inhibitor) in AppNL-G-F and AppNL-G-F x Thy1-Tau22 mice, both before and after amyloid plaque deposition... Our observations revealed a stage-dependent dual role of microglia in amyloid pathology. Microglia seed plaques in early disease stages and compact them at later stages. The severity of Tau pathology appears to follow changes in amyloid load, regardless of the absence of microglia."

Alzheimer's Disease • CNS Disorders • THY1

Repeated RFA remodels the PDAC microenvironment and synergizes with CSF1R blockade and checkpoint inhibition to enhance anti-tumor immunity (AACR 2026) - "Given our prior findings with a single RFA session + ICB, we evaluated repeated RFA in combination with ICB and tested whether adding CSF1R blockade (PLX3397) could counteract RFA-induced myeloid immune suppression. Repeated RFA significantly reduced tumor growth rates and increased tumor necrosis in both treated and contralateral lesions compared to a single RFA session... Repeated RFA intensifies tumor necrosis, suppresses tumor progression, and remodels the PDAC TME, but concurrently induces a compensatory Csf1/Csf1r-driven M2-like macrophage response. Macrophage reprogramming through CSF1R blockade enhances both RFA- and ICB-mediated anti-tumor immunity. These findings support integrating repeated local ablative therapy with myeloid-targeting agents and checkpoint blockade to improve immunologic control of pancreatic cancer."

Checkpoint inhibition • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CSF1R • KRAS • PDX1

Novel targeted therapies for malignant ascites in pancreatic cancer (AACR 2026) - "We are in the process of assessing the efficacy of an anti-VEGFA antibody (2G11-2A05) and a CSF1R inhibitor (PLX3397) in the same model. Results from the studies could establish preclinical evidence supporting the utility of these novel therapeutic regimens for treating MA in pancreatic cancer patients and lead to clinical trials to address this critical unmet need."

IO biomarker • Oncology • Ovarian Cancer • Pancreatic Cancer • Peritoneal Cancer • Solid Tumor • CD163 • CD8 • CD80

Clinicopathologic Characteristics of Pexidartinib- Treated Tenosynovial Giant Cell Tumor (USCAP 2026) - "Design: We performed a retrospective search of all TGCT at a single institution from 2019-2025 and reviewed cases with treatment by CSF1R inhibitor (Pexidartinib or Vimseltinib). Pexidartinib-treated TGCT can show unique radiologic and histologic changes compared to conventional untreated TGCT. Histologic changes range from reduction in giant/mononuclear cells to complete absence of lesional tissues. Recognition on the histologic spectrum and treatment effects of CSF1R inhibition in TGCT is critical for its accurate diagnosis."

Clinical • Fibrosis • Giant Cell Tumor of Bone • Immunology • Oncology • Tenosynovial Giant Cell Tumor

Keratin-Positive Giant Cell-Rich Tumor: Expanded Clinicopathologic Spectrum Including Tumors with Limited Keratin Expression and Intra-Articular Origin (USCAP 2026) - "Treatment included partial excision (3) followed by pexidartinib (1), denosumab (1) or radiation (1). We describe 6 KPGCT with previously unreported features including limited or absent keratin expression and intra-articular origin, expanding our evolving understanding of these recently described neoplasms."

Clinical • Giant Cell Tumor of Bone • Oncology • Tenosynovial Giant Cell Tumor • HMGA2 • NCOR2

The impact of CSF1R inhibitor-mediated microglial depletion in rodent models of Alzheimer's and Parkinson's disease: a systematic review and meta-analysis. (PubMed, Front Aging Neurosci) - "This systematic review and meta-analysis aim to evaluate the effects of microglial depletion using colony-stimulating factor 1 receptor (CSF1R) inhibitors, such as PLX3397 and PLX5622, in preclinical models of AD and PD. Further studies are needed, particularly those assessing post-onset intervention, sex-specific effects, and broader behavioral and pathological endpoints to better understand the therapeutic potential of microglial modulation. https://www.crd.york.ac.uk/prospero/, identifier CRD420251075163."

Journal • Preclinical • Retrospective data • Review • Alzheimer's Disease • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease

CSF1R⁺ myeloid cells mediate resistance to CAR-T-cell therapy in lung cancer brain metastases (ITOC 2026) - "TAM/M depletion was achieved via CSF1R inhibition using a PLX 3397 diet...Targeting CSF1R on TAM/M improved CAR T-cell trafficking, intratumoral persistence and therapeutic efficacy resulting in a survival benefit. These results pave the way for combinatorial strategies incorporating CSF1R inhibition to further enhance CAR T-cell functionality and improve outcomes in the treatment of brain metastases."

CAR T-Cell Therapy • Brain Cancer • Lung Cancer • Oncology • Solid Tumor • CSF1R

IDENTIFYING TENOSYNOVIAL GIANT CELL TUMOR (TGCT) IN SECONDARY DATA: METHODOLOGICAL CHALLENGES, EMERGING OPPORTUNITIES, AND FUTURE DIRECTIONS (ISPOR 2026) - "Inclusion criteria required ≥1 inpatient/emergency department or outpatient claim, and/or received TGCT-targeted systemic therapy (e.g., pexidartinib, vimseltinib). Terminological inconsistencies and coding limitations complicate TGCT identification in secondary datasets. Standardizing diagnostic criteria and coding practices across geographies is crucial for improving global TGCT surveillance, particularly as targeted systemic therapies gain prominence. Descriptive analyses of the algorithm indicate that the identification strategy has face validity and clinical plausibility; integration with complementary data sources, such as pathology, imaging, and natural language processing of electronic health records will be essential for accuracy."

Giant Cell Tumor of Bone • Oncology • Orthopedics • Tenosynovial Giant Cell Tumor

Management of tenosynovial giant cell tumor: approved and investigational therapies. (PubMed, Expert Rev Anticancer Ther) - "Pexidartinib and vimseltinib demonstrate comparable efficacy in TGCT with objective response rates (ORR) of 39% and 40%, respectively, at week 25 of treatment; however, vimseltinib offers improved hepatic safety and tolerability, supporting its use as the preferred first-line systemic therapy. Emerging agents, including pimicotinib and emactuzumab, show potential for higher response rates and favorable safety profiles and may further reshape the TGCT treatment paradigm pending phase 3 trial results."

Journal • Review • Giant Cell Tumor of Bone • Oncology • Tenosynovial Giant Cell Tumor

Macrophage polarization in hematologic cancers: mechanisms and therapeutic strategies. (PubMed, Blood Res) - "Preclinical studies demonstrate CSF-1R inhibitors (e.g., pexidartinib) disrupt LSC-TAM crosstalk, while CAR-M therapy synergizes with phagocytosis-promoting agents. Despite challenges, macrophage-targeted therapies offer transformative potential by remodeling the TME, overcoming resistance, and augmenting immunotherapy. This review outlines mechanistic insights and translational strategies to harness macrophage plasticity for leukemia treatment."

Journal • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • CCL2 • CCR2 • CD163 • IL10 • IL4 • KLF4 • MRC1 • PPARG • SIRPA • STAT6 • TGFB1

Patient-derived organoid xenografts model esophageal cancer cachexia and enable assessment of anti-inflammatory drug repositioning. (PubMed, iScience) - "Using this platform, we tested two macrophage-targeting interventions: 10 mg/kg/day rosiglitazone, a PPAR-γ agonist, and 40 mg/kg/day pexidartinib (PLX3397), a CSF1R inhibitor. Transcriptomic analyses confirmed suppression of pro-cachectic cytokine signaling. This study presents a clinically relevant platform for preclinical cachexia research and supports macrophage modulation as a potential anti-cachexia strategy."

Journal • Cachexia • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma

Pharmacological Depletion of Retinal Mononuclear Phagocytes Is Neuroprotective in a Mouse Model of Mitochondrial Optic Neuropathy. (PubMed, Invest Ophthalmol Vis Sci) - "We hypothesized that pharmacological depletion of MNPs with the colony-stimulating factor-1 receptor inhibitor pexidartinib would enhance RGC neuroprotection by hypoxia...This therapeutic effect is additive to that of hypoxia. Combating retinal neuro-inflammation may therefore be a useful adjunct therapy in mitochondrial optic neuropathies like Leber hereditary optic neuropathy (LHON)."

Journal • Preclinical • Inflammation • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Metabolic Disorders • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain

Identification of repopulated microglia-associated genes in microglia depleted/repopulated mice after spinal cord injury. (PubMed, Brain Res) - "This study aimed to investigate the effects of repopulated microglia on neural repair and functional recovery and identify repopulated microglia-associated repair-promoting genes after spinal cord injury (SCI) in mice following depletion of microglia via the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX3397...This study reveals that repopulated microglia may exert neuroprotective effects by modulating the immune microenvironment. The 336 repopulated microglia-associated genes identified in this study, and the identified key genes that are preferentially upregulated in repopulated microglia may represent novel therapeutic targets for SCI."

Journal • Preclinical • CNS Disorders • Orthopedics • CCR2 • IL15

A Tumor-Bearing Mouse Model for Studying Cisplatin-Induced Hearing Loss (ARO 2026) - "We have successfully established a tumor-bearing mouse model that also develops hearing loss in response to cisplatin. This model enables us and others to evaluate potential protective therapies in the presence of tumor, reflecting the clinical use of cisplatin, while ensuring that otoprotective therapies do not compromise cisplatin’s anti-tumor efficacy. Using this model, we are currently testing whether pexidartinib (PLX3397), the FDA-approved drug previously shown to completely protect against cisplatin-induced hearing loss, affects the therapeutic efficacy of cisplatin."

Preclinical • Oncology • Oral Cancer • Otorhinolaryngology • Squamous Cell Carcinoma

Investigating vimseltinib in tenosynovial giant cell tumors. (PubMed, Expert Opin Pharmacother) - "Furthermore, there is an absence of severe toxicities that have arisen with other agents in the TGCT treatment space, specifically liver failure. Vimseltinib is a favorable option for patients with TGCTs and further efforts to determine its place in the sequence of overall management are needed."

Journal • Review • Giant Cell Tumor of Bone • Hepatology • Liver Failure • Oncology • Tenosynovial Giant Cell Tumor • CSF1R

High Risk of Drug-Drug Interactions Caused by Pexidartinib via UDP-Glucuronosyltransferases Inhibition. (PubMed, Chem Res Toxicol) - "The results of in vitro-in vivo extrapolation (IVIVE) indicated that coadministration of pexidartinib at a clinically approved dose (400 mg twice daily) with the drugs primarily cleared by UGT1A1, UGT1A6, UGT1A7, UGT1A9, and UGT2B15 would result in a higher risk of DDI. In summary, our results provide useful information for the mechanism underlying pexidartinib-induced hepatotoxicity and clinical safe medication of pexidartinib."

Journal • Giant Cell Tumor of Bone • Oncology • Tenosynovial Giant Cell Tumor • UGT1A6 • UGT1A7 • UGT1A9 • UGT2B15

Results from Phase 1 Extension Study Assessing Pexidartinib Treatment in 6 cohorts with Solid Tumors including TGCT, and Abnormal CSF1 Transcripts in TGCT. (PubMed, Clin Cancer Res) - "These results offer insight into outcome patterns in cancers whose biology suggests use of a CSF1R inhibitor. Pexidartinib results in tumor regression in TGCT patients, providing prolonged control with an acceptable safety profile."

Clinical • Journal • P1 data • Giant Cell Tumor of Bone • Immunology • Oncology • Pain • Solid Tumor • Tenosynovial Giant Cell Tumor • CSF1 • FLT3

LONG-TERM EFFICACY AND SAFETY OF PEXIDARTINIB IN PATIENTS WITH TENOSYNOVIAL GIANT CELL TUMOR: RESULTS FROM THE PHASE 3 ENLIVEN STUDY (CTOS 2022) - No abstract available

Clinical • P3 data • Giant Cell Tumor of Bone • Immunology • Oncology • Tenosynovial Giant Cell Tumor

CORR Insights®: Pexidartinib Provides Modest Pain Relief in Patients With Tenosynovial Giant Cell Tumor: Results From ENLIVEN. (PubMed, Clin Orthop Relat Res) - No abstract available

Journal • Giant Cell Tumor of Bone • Immunology • Oncology • Pain • Tenosynovial Giant Cell Tumor

Targeting the DKK1/CSF1 Signaling Axis to Reprogram M2 Macrophages and Reverse Chemoresistance in Head and Neck Squamous Cell Carcinoma. (PubMed, Eur J Pharm Sci) - "This study underscores the dual role of CSF1 in regulating both tumor survival and M2 macrophage activation in HNSCC. Targeting the DKK1/CSF1 axis may represent a promising strategy to overcome chemoresistance by disrupting tumor-macrophage crosstalk and reprogramming the immunosuppressive microenvironment."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • AKT1 • CSF1 • CXCL12 • DKK1 • IL10

Head-to-head preclinical treatment design prioritizes promising therapies for neurofibromatosis type 1 optic glioma clinical translation. (PubMed, Neurooncol Adv) - "Nf1 OPG mice were treated with standard of care (SOC; carboplatin), clinically evaluated (everolimus, mirdametinib), and investigational (pexidartinib, HBS-101, lamotrigine) drugs during the period of most rapid tumor growth (6-12 weeks of age). This referential preclinical study design affords direct head-to-head comparisons of investigational therapies relative to SOC treatment using clinically meaningful outcomes (OPG growth and RNFL thickness). Using this strategy, lamotrigine emerged as the most promising therapy for limiting tumor progression and vision loss in Nf1-OPG mice, relevant to clinical translation for children with NF1-OPG."

Head-to-Head • Journal • Preclinical • Brain Cancer • Genetic Disorders • Glioma • Neurofibromatosis • Oncology • Pediatrics • Solid Tumor • CCL2 • CCL3 • NF1

RIC-specific cytoprotective profile mediated by microglia in a mouse model of acute ischaemic stroke. (PubMed, Stroke Vasc Neurol) - "These findings reveal sex-specific efficacy of RIC, with mechanistic insights obtained in male animals suggesting a dual mode of action via modulation of microglial function and promotion of endogenous neurorepair pathways."

Journal • Preclinical • Cardiovascular • Ischemic stroke

Efficacy of Targeted Agents and Immune Checkpoint Inhibitors in Patients with Malignant Histiocytosis (ASH 2024) - "TAs included BRAF inhibitor (vemurafenib [1]), MEK inhibitors (binimetinib [1], cobimetinib [2], trametinib [2]) and others (dasatinib [1], pazopanib [1], pexidartinib [1]), while ICIs were exclusively pembrolizumab (5)...TAs included BRAF inhibitor only (vemurafenib [3], dabrafenib [3]), MEK inhibitor only (trametinib [5]), BRAF + MEK inhibitors (2), and others (apatinib, anlotimib, bevacizumab, daratumumab, dasatinib, imatinib, pazopanib, sorafenib, or combinations [9]), while ICIs included pembrolizumab (4), nivolumab (4), tislelizumab (1), and sintilimab (1)...Conclusion TAs and ICIs can be considered in the management of MH. The responses to ICI therapy may be associated with the degree of PDL1 expression"

Checkpoint inhibition • Clinical • IO biomarker • Hematological Malignancies • Oncology • Sarcoma • Solid Tumor • DOCK8 • MAP2K1 • PD-L1 • PTPN11

PLX3397 attenuated tumor growth and remodeled tumor microenvironment of recurrent glioblastoma. (PubMed, Sci Rep) - "PLX3397 treatment significantly attenuated tumor growth and remodeled TME. Collectively, our study firstly analyzed TME combine a large number of database samples and clinical samples, and made the first application of PLX3397 in a murine recurrent GBM model, thereby providing a novel therapeutic strategy and experimental foundation for recurrent GBM research."

Biomarker • Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor