Jakafi (ruxolitinib) / Novartis, Incyte - LARVOL DELTA

Investigating druggability of myeloid and lymphoid lineage gene mutations in advanced phase CML by employing drug discovery tools: Implications in fatal blast crisis CML precision oncology (AACR 2025) - "We also found that some FDA-approved drugs for different hematological malignancies (e.g. VENETOCLAX, DECITABINE, AZACITIDINE, BORTEZOMIB, ZANUBRUTINIB, IVOSIDENIB, TAZEMETOSTAT, RUXOLITINIB, PACRITINIB, ARSENIC TRIOXIDE etc.) can effectively target multiple gene groups mutated in our advanced phase CML patients (Table 1-4, Figures 1-4). NGS analysis of AP- & BC-CML found mutations in many AML-/ALL-lineage genes, which is much higher than previously reported. NGS analysis of AP- & BC-CML found mutations in many AML-/ALL-lineage genes, which is much higher than previously reported. This shows a huge genetic similarity between BC-CML and AML/ALL. FDA-approved and various novel experimental drugs under clinical trials are available against some of the genes we reported."

IO biomarker • Metastases • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • AKT1 • BCL2 • DNMT3A • IDH1 • JAK2 • NPM1 • TET2

Case Report: Successful use of emapalumab in adult B-cell acute lymphoblastic leukemia experiencing severe neurotoxicity and hemophagocytic lymphohistiocytosis-like features after CAR-T cell therapy. (PubMed, Front Immunol) - "We report an adult B-cell acute lymphoblastic leukemia (B-ALL) patient treated with brexucabtagene autoleucel (brexu-cel)...Treatment included tocilizumab, high-dose corticosteroids, anakinra, siltuximab, and ruxolitinib...The patient recovered from IEC-HS and underwent allogeneic stem cell transplantation. This case highlights the role of emapalumab in managing refractory IEC-HS and persistent neurotoxicity in adults, underscoring the need for targeted interventions in severe CAR-T complications."

IO biomarker • Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Leukemia • Oncology • Rare Diseases • Transplantation • IFNG

Total Therapy XVII for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia and Lymphoma (clinicaltrials.gov) - P2/3 | N=790 | Active, not recruiting | Sponsor: St. Jude Children's Research Hospital | Trial completion date: Mar 2028 ➔ Sep 2028

Trial completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • BCL2

Efficacy and safety of fedratinib in myelofibrosis patients after ruxolitinib: A systematic review and meta-analysis. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Retrospective data • Review • Myelofibrosis

IMproveMF update: Phase 1/1B trial of imetelstat (IME)+ruxolitinib (RUX) in patients (pts) with intermediate (INT)-1, INT-2, or high-risk (HR) myelofibrosis (MF). (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT05371964 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • P1 data • Myelofibrosis

Treatment Advances in Graft-Vs-Host Disease: A 48-Year-Old Man With Chronic Graft-Vs-Host Disease : Episode 4: Ruxolitinib Therapy for cGVHD: Insights on Patient and Safety Monitoring (Targeted Oncology) - "A panelist discusses how managing adverse events (AEs) in patients with chronic graft-vs-host disease (cGVHD) treated with ruxolitinib requires a structured monitoring approach that balances therapeutic efficacy with patient safety through regular clinical evaluations, laboratory assessments, and proactive management strategies tailored to individual risk profiles."

Video

Baseline, Drug-Related and Persistent Anemia and/or Thrombocytopenia Predict Responses and Prognosis in Myelofibrosis Patients Treated With Ruxolitinib. (PubMed, Hematol Oncol) - No abstract available

Journal • Anemia • Hematological Disorders • Myelofibrosis • Thrombocytopenia

NCI-2013-00704: Ruxolitinib Phosphate and Azacytidine in Treating Patients With Myelofibrosis or Myelodysplastic Syndrome/Myeloproliferative Neoplasm (clinicaltrials.gov) - P2 | N=125 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Apr 2025 ➔ Apr 2027 | Trial primary completion date: Apr 2025 ➔ Apr 2027

Trial completion date • Trial primary completion date • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • Thrombocytosis

JAK/STAT Inhibition in CNS Kohlmeier-Degos Disease (clinicaltrials.gov) - P1/2 | N=1 | Completed | Sponsor: National Heart, Lung, and Blood Institute (NHLBI) | Trial primary completion date: Jan 2024 ➔ Feb 2025

Trial primary completion date

MAGIC V: MAGIC Ruxolitinib for aGVHD (clinicaltrials.gov) - P2 | N=98 | Recruiting | Sponsor: John Levine

New P2 trial • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Transplantation

Genome-wide CRISPRi screening identifies histone modification as a synergistic partner with JAK/STAT inhibition for enhancing anti-tumor activity in CTCL, validated in PDX-derived tumor cells (AACR 2025) - "Using primary human CTCL cells derived from PDX models, we observed synergistic induction of apoptosis with ruxolitinib or golidocitinib in combination with either romidepsin or 5-azacitidine, as demonstrated by caspase activation assays. These findings demonstrated in primary human CTCL cells from the PDX models—a clinically relevant experimental system—highlight the translational significance of this approach. Ongoing therapeutic trials with PDX animals will further investigate these promising findings."

Epigenetic controller • Tumor cell • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Polycythaemia vera. (PubMed, Nat Rev Dis Primers) - "Recommendations for PV treatment include control of vascular risk factors, therapeutic phlebotomy and low-dose aspirin in all patients. Hydroxyurea or interferons remain the preferred first-line cytoreductive agents, with the JAK1 and JAK2 inhibitor, ruxolitinib, currently approved for the treatment of patients who are resistant to, or intolerant of, hydroxyurea. Future recommendations might be to treat the majority of patients with these agents as long-term benefits of treatment begin to emerge."

Journal • Review • Acute Myelogenous Leukemia • Cardiovascular • Hematological Disorders • Hematological Malignancies • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • Thrombocytosis • Thrombosis

In Vitro Drug Profiling to Guide Treatment for Relapse/Refractory AML (ASH 2024) - "Significant correlation was observed among drugs of the same classes, for example between inhibitors of PARP (e.g. niraparib-talazoparib, r=0.78, p=1.3e-22), proteasome (e.g. bortezomib-ixazomib, r=0.90, p=4.2e-36), JAK (ruxolitinib-tofacitinib, r=0.91, p=8.3e-35), MEK (cobimetinib-trametinib, p=0.93, p=8.8e-47) and CDK (abemaciclib-palbociclib, p=0.56, p=2.7e-10), confirming that the readout is biologically meaningful. Intriguingly, there were unexpected correlations between specific pairs of drugs of different classes, for instance homoharringtonine (protein translation inhibitor)-abemaciclib (CDK inhibitor) (r=0.65, p=4.3e-17) and between specific gene mutations and drug sensitivity was observed, e.g. sensitivity of CEBPAbZIP mutated samples to PARP inhibitors (p=0.00156), and of AML with inv(16) to MEK inhibitors (p=0.0016)...Drug response to daunorubicin showed good prediction of chemo-resistance in patients who had non-remission after "7+3" (ROC curve AUC..."

Preclinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • ANXA5 • FLT3

Ruxolitinib Based GVHD Prophylaxis Regimen Before, During, and After Hematopoietic Cell Transplantation in Older Adult Patients With Acquired Aplastic Anemia (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Fred Hutchinson Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Anemia • Aplastic Anemia • Graft versus Host Disease • Hematological Disorders • Immunology • Transplantation

Thrombotic Risk and Symptom Burden in Patients With Polycythemia Vera | Identify When to Intervene With Jakafi® (ruxolitinib) (ONS 2025) - "Incyte is a Wilmington, Delaware-based, global biopharmaceutical company focused on finding solutions for serious unmet medical needs through the discovery, development, and commercialization of proprietary therapeutics. For additional information on Incyte, please visit Incyte.com or follow us on social media: LinkedIn, X, Instagram, Facebook, YouTube."

Clinical • Oncology • Polycythemia Vera • Solid Tumor

In vitro and in vivo screening platform for discovery of JAK2 inhibitors (AACR 2025) - "We successfully established both in vitro and in vivo screening platform for JAK2 inhibitors, providing a valuable tool for optimizing therapeutic strategies for diseases associated with abnormal JAK2 activation."

Preclinical • Essential Thrombocythemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • CSF2 • JAK1 • JAK3 • STAT5 • TYK2

INCB057643, a bromodomain and extra-terminal (BET) protein inhibitor, improved bone marrow function and shifted megakaryopoiesis to erythropoiesis in patients with myeloproliferative neoplasms (MPNs) (AACR 2025) - P1, P1/2 | "INCB057643, a novel, orally bioavailable BET inhibitor, is being evaluated in clinical trials as monotherapy and in combination with ruxolitinib in patients with MPNs (NCT02711137; NCT04279847). In conclusion, the results show that INCB057643 specifically inhibits pathogenic MK differentiation, reduces inflammatory cytokine production, and decreases fibrosis. INCB057643 treatment also improves bone marrow function, which results in increased erythroid differentiation and reduced anemia symptoms."

Clinical • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • CD34 • ITGB3 • JAK2 • TFRC • TIMP3

Novel allosteric STING agonists in combination with DNA methyltransferase inhibitors induce an interferon-driven apoptotic response in TP53-mutated acute myeloid leukemia (AACR 2025) - "We perfomed MTS assays in TP53-mutated and -WT AML cell lines and primary cells (N=4) treated with CPD 1 and DNMTi decitabine (DAC) combination in vitro...Treatment with the IFN inhibitor ruxolitinib or the pan-caspase inhibitor ZVAD rescued IFN-driven apoptosis. Finally CPD 1 in combination with DAC significantly reduced leukemia burden in humanized AML mouse models. These results support development of a clinical trial combining CRD3874-SI with DAC for patients with TP53-mutated AML."

Combination therapy • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • ANXA5 • CXCL10 • CXCL11 • IFI27 • IFIH1 • IFIT2 • MX1 • OASL • STING • TNFA • TNFSF10 • TP53

The role of CD53+ subsets and the JAK/STAT3 pathway in regulating cancer stemness and immune escape in esophageal squamous cell carcinoma (AACR 2025) - "Furthermore, in vivo study showed that JAK inhibitor Ruxolitinib and STAT3 inhibitor C188-9 could efficiently reduce tumor growth and enhance T cell infiltration in CD53+ mouse ESCC cell lines, suggesting a role in tumor proliferation and T cell editing. This study aims to elucidate the biological function of CD53+ subset ESCC cells in tumor progression and verify their role in T cell regulation, offering new therapeutic targets for ESCC treatment."

Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Hematological Malignancies • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD53 • IL6 • MYC • PD-L1

Ruxolitinib diminishes cell proliferation and invasiveness in BRAF mutated metastatic melanoma (AACR 2025) - "In cells containing a BRAF mutation, Ruxolitinib caused a decrease in erythropoietin (EPO) induced proliferation. Modulation of EPOR with EPO, 10nM Ruxolitinib, and 10nM Ruxolitinib with EPO yielded a mean fold change over control in proliferation of 1.55 (95% CI: 1.16-1.94), 0.96 (95% CI: 0.84-1.09), and 1.24 (95% CI: 0.77-1.72), respectively (p=0.0254). In metastatic melanoma cells, Ruxolitinib significantly reduced invasiveness by a 0.48-fold change over control in proliferation."

Metastases • Melanoma • Oncology • Solid Tumor • BRAF

Synergistic growth-inhibitory efficacy of LSD1 and BCL-XL inhibitors in JAK2+ AML/MPN cells (AACR 2025) - "We explored the synergy between the LSD1i Iadademstat (Selleckchem), and BCL-2/BCL-XL inhibitor, Navitoclax, or the platelet-sparing BCL-XL degrader, DT2216 (Dialectic Therapeutics). In summary, JAK2+-mutant post-MPN AML cell lines and isogenic Ruxolitinib-resistant lines showed sensitivity to BCL-XL inhibitors and a synergistic increased sensitivity to these compounds when combined with low dose LSD1 inhibitor, Iadademstat. Mechanisms behind the synergy are being studied and will be reported.Summary of Glo Titer Assays and Annexin 5 Flow Cytometry Data with mean Synergy ScoresGlo Titer AssayNavitoclaxDT2216LSD1iLSD1i+NavitoclaxLSD1i+DT2216Hel ParentalIC501.3±0.2µM2±0.8µMNot Reached6.5±3 nM0.25±0.08 µMHel RRIC500.5±0.3µM1.8±0.7µMNot Reached6±3nM0.3±0.15 µMSet 2 ParentalIC500.4±0.4µM2.5±1 µMNot Reached6.5±02.5nM2±1.3 µMSet 2..."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • Oncology • BAX • BCL2 • BCL2L1 • JAK2

Heat shock protein inhibitors suppress cytokine-induced DUOX2 mRNA and protein expression in human pancreatic cancer cells in a JAK-STAT dependent manner [WITHDRAWN] (AACR 2025) - "Using a panel of human pancreatic cancer cell lines (BxPC-3, AsPC-1 and CFPAC-1), we found that two different Hsp90 inhibitors, Tanespimycin (17-AAG) and Ganetespib (STA-9090), inhibit JAK1 and JAK2 kinases, blocking cytokine-induced, JAK-regulated STAT phosphorylation...Furthermore, the JAK1/2 inhibitor Ruxolitinib inhibits IL-4 induced and JAK-mediated STAT6 phosphorylation, and DUOX2 mRNA and protein expression in BxPC-3 cells...Either remaining Hsp90 protein or other isoforms of Hsp90 in cells may compensate decreased Hsp90 function after siRNA knockdown. Our data suggests that Hsp90 inhibitors, through blocking the cytokine-activated JAK-STATs oncogenic signaling pathway and their downstream genes such as DUOX2, VEGF-A, MMP-7 and PD-L1expression, may be a valuable therapeutic approach for inflammation-associated pancreatic cancer."

IO biomarker • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CDC37 • DUOX2 • HIF1A • IFNA1 • IL17A • IL4 • MMP7 • PD-L1 • STAT1 • STAT3 • STAT6

Distinct kinase signatures define therapeutically relevant subtypes in colorectal cancer (AACR 2025) - "Functional validation was conducted using dose-response assays with specific inhibitors: Ruxolitinib (JAK inhibitor) and Dasatinib (SRC inhibitor). This study highlights the utility of kinase activity profiling as a robust approach for molecular stratification of colorectal cancer, identifying EPH and SRC kinase activity as potential biomarkers. The validation of differential inhibitor sensitivity supports the potential clinical utility of these markers in guiding personalized therapies. By integrating kinome analysis with transcriptomics, we provide a comprehensive framework for understanding the molecular underpinnings of CRC heterogeneity."

Colorectal Cancer • Oncology • Solid Tumor

JAK/STAT1-interferon-ISGylation networks in breast cancer resistance to inhibitors of FOXM1 and CDK4/6 (AACR 2025) - "We show that ER-positive FOXM1 inhibitor resistant cells and CDK4/6 inhibitor (Palbociclib and Abemaciclib) resistant cells all exhibit an increased JAK/STAT1-interferon responsive gene and protein signaling network with elevated interferon stimulated gene15 (ISG15). ISG15 protein is present as high intracellular free ISG15 and also as increased ISGylated protein conjugates that can be markedly reduced by treatment of resistant cells with the JAK1/2 inhibitor ruxolitinib...Importantly, Palbo and Abema resistant cells and organoids can still be effectively growth inhibited by FOXM1 inhibitor NB73, and likewise, FOXM1 inhibitor resistant cells and organoids are sensitive to suppression of viability by Palbo or Abema. This suggests that sequential treatment approaches might be effective in overcoming resistance and enabling the suppression of these drug-resistant cancers."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • FOXM1 • STAT1 • UBE2L6

The role of NCAM1(CD56) in mediating venetoclax resistance (AACR 2025) - "Our group recently found that CD56 expression on myeloid blasts is associated with worse overall survival to treatment with the BCL2 inhibitor, Venetoclax (VEN), including VEN combined with hypomethylating agents or with the JAK inhibitor, Ruxolitinib. Genetic deletion of CD56 sensitizes AML cells to VEN treatment and decreases pMAPK1/3 as well as BCL2 protein levels. CD56 signaling occurs through the PTK2/RAS/MAPK signaling pathway, however a direct regulatory role of CD56 on BCL2 expression has not yet been reported. Future therapeutics targeting CD56 may be able to improve response and survival in patients with CD56 positive AML particularly after VEN resistance."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD14 • FGFR1 • ITGAM • KIT • MAPK1 • MCL1 • NCAM1 • RUNX3