Bosulif (bosutinib) / Pfizer - LARVOL DELTA

Bosutinib for Successful Treatment-Free Remission in Chronic Myeloid Leukemia. (PubMed, Cancer Med) - "Bosutinib can be safely discontinued under certain conditions, similar to other tyrosine kinase inhibitors. Additionally, T-cell profile analysis before and after bosutinib discontinuation may predict successful TFR."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • CD8

Bosutinib mitigates inflammation in experimental sepsis. (PubMed, Eur J Clin Invest) - "Bosutinib pretreatment attenuated dysregulated inflammatory responses and neurovascular changes in experimental sepsis."

Journal • Infectious Disease • Inflammation • Septic Shock • HCK

Comprehensive Analysis of ABL1 Variant Resistance to Multiple Kinase Inhibitors via Prime Editing (ASGCT 2025) - "We then assessed the resistance profiles of these SAAVs against a panel of five TKIs—imatinib, nilotinib, bosutinib, ponatinib, and asciminib—representing all four TKI generations, using CML-relevant K562 cells. The comprehensive resistance landscape generated in this study serves as a valuable resource to refine clinical decision-making and enhance precision medicine strategies for CML patients by providing an evidence-based framework for drug selection based on ABL1 mutation status. Disease Focus of Abstract:Cancer Hematologic"

Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • ABL1

Which Is the Best Tyrosine Kinase Inhibitor for Newly Diagnosed Chronic Myelogenous Leukemia? (PubMed, Am Soc Clin Oncol Educ Book) - "Currently, five tyrosine kinase inhibitors (TKIs-imatinib, dasatinib, nilotinib, bosutinib, and asciminib) are available for frontline therapy, but no single TKI is optimal for all patients. While the overall treatment failure rate was lower with asciminib, the rate of BCR::ABL1 mutations that emerged with asciminib appeared to be higher. The risk of emergent mutations appears to be highly associated with the presence of ASXL1 mutations in the CML cells at diagnosis, but more work is needed to understand the implications of this finding."

Journal • Review • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • ASXL1

NXP900, a novel YES1/SRC kinase inhibitor currently in clinical development, blocks YAP1 signaling in NSCLC cell lines (AACR 2025) - "Conversely, multi-kinase inhibitors dasatinib and bosutinib target the "open" conformation (type 1), thus promoting SFK association with signalling partners3. NXP900 prevents YAP1 nuclear localization and cell cycle progression in a panel of NSCLC cell lines, decreasing expression of total YAP1 and YES1. Our data suggests that NXP900, currently in a Phase1 dose escalation study, is an attractive and translatable combination partner that could synergize with existing targeted therapies against NSCLC when the Hippo pathway is dysregulated."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • YAP1

NXP900, a phase 1, first-in-class YES1/SRC inhibitor demonstrates potent single agent activity and synergy with ALK inhibitors in ALK resistant NSCLC models (AACR 2025) - "In contrast, multi-kinase inhibitors, including dasatinib and bosutinib, lock SRC in the active "open" conformation (type 1 inhibitors) promoting the association of SFK and signaling partners via allosteric facilitation (Higuchi et al. Despite high response rates to lorlatinib and long duration of response, acquired resistance almost universally arises. Here we demonstrate that NXP900 can potently inhibit cell proliferation of ALK resistant cell lines as a single agent and is synergistic with lorlatinib in NSCLC models harboring different variants of the ALK gene fusion. Altogether, these data suggest that NXP900 may have therapeutic potential in cancers with acquired resistance to ALK inhibitors."

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EML4

Overcoming osimertinib resistance in NSCLC with NXP900, a phase 1, highly selective and potent first-in-class total YES1/SRC inhibitor (AACR 2025) - "In contrast, multi-kinase inhibitors, including dasatinib and bosutinib, block SRC in the active "open" conformation (type 1 inhibitors) promoting the association of SFK and signaling partners via allosteric facilitation (Higuchi et al. Despite high response rates to osimertinib in EGFR mutant lung cancer patients acquired resistance almost universally arises. Here we demonstrate that NXP900 in combination with osimertinib demonstrates potent synergy and prolonged inhibition of tumor growth in in vitro and in vivo NSCLC models of acquired osimertinib resistance. Altogether, these data suggest that NXP900 may have therapeutic potential in EGFR mutant cancers with acquired resistance to osimertinib."

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Development and application of a mechanistic pharmacokinetic pharmacodynamic (PKPD) model to predict anti-chronic myeloid leukemia (CML) effects of tyrosine kinase inhibitors (AACR 2025) - "Although tyrosine kinase inhibitors (TKIs) for BCR::ABL1 like imatinib, dasatinib, nilotinib, bosutinib, asciminib and ponatinib are available for CML treatment, novel treatments are needed for CML that is resistant or patients who are intolerant to available therapies. This generalizable PKPD model, using available PK and in vitro potency data, was developed and accurately predicted outcomes of five approved BCR::ABL1 TKIs in patients with newly-diagnosed CML, suggesting the mechanistic PKPD model may be used to predict efficacy for novel TKIs."

PK/PD data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • CRKL • STAT5 • STAT5AWqe

Endocrine therapy-resistant luminal A breast cancer cell lines are sensitive to the novel YES1/SRC tyrosine kinase inhibitor, NXP900 (AACR 2025) - "Recent findings using ER+ cell lines show increased sensitivity with NXP900 as opposed to other kinase inhibitors, such as dasatinib or bosutinib. Additionally, our longitudinal data suggests that NXP900 is a strong therapeutic candidate to treat ER+ cell lines with acquired endocrine resistance. This study supports the potential translation of NXP900 into an adjuvant clinical setting, alongside endocrine therapies, to improve breast cancer treatment in patients with ER+ tumors."

Late-breaking abstract • Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER

Severe Aortic Stenosis and Chronic Myeloid Leukemia: Considerations for Valve Management. (PubMed, JACC CardioOncol) - No abstract available

Journal • Review • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

DIORS: Enhancing drug-target interaction prediction via structure and signature integrated-driven approach and discovering potential targeted molecules. (PubMed, Pharmacol Res) - "In Piezo1-targeted molecule prediction, among the top ten predicted molecules by DIORS, four of them, namely gefitinib, rifaximin, bosutinib and vandetanib, exhibited binding affinities. In the prediction of TLR4/MD2-targeted anti-inflammatory molecules, among the top ten predicted molecules, three of them, namely enoxolone, dabrafenib and ponatinib, exhibit both high binding affinities and anti-inflammatory activities. The results demonstrated that DIORS can serve as a better approach with high performance to predict and find new targeted drugs by combining structural and signature information."

Journal • TLR4

Ponatinib and other clinically approved inhibitors of Src and Rho-A kinases abrogate dengue virus serotype 2- induced endothelial permeability. (PubMed, Virulence) - "Here, we show that the FDA-approved SFK inhibitors Bosutinib, Vandetanib and Ponatinib, as well as the ROCK inhibitors, Netarsudil and Ripasudil significantly inhibit DENV2-induced endothelial permeability. Comparable effects were observed even when ponatinib treatment was initiated after symptom onset. The results highlight ponatinib as an effective therapeutic option in severe dengue; and also a similar potential for other FDA- approved SFK and ROCK inhibitors."

Journal • Dengue Fever • Hematological Disorders • Infectious Disease • Thrombocytopenia • CDH5 • IL1B • RHOA • TNFA

ALLOGENEIC TRANSPLANTATION IN A PATIENT WITH REFRACTORY CHRONIC MYELOID LEUKEMIA (EBMT 2025) - "The F359V mutation in the ABL1 gene was identified by Next-Generation Sequencing in November 2022, a mutation affecting the catalytic domain and conferring moderate resistance to Imatinib and Nilotinib.Second-line treatment with Ponatinib was initiated in chronic phase in November 2022 but did not result in molecular response.In April 2023, the patient was diagnosed with lymphoid blastic crisis. Induction therapy was started using the LAL Ph 2008 protocol from the PETHEMA group, with Ponatinib substituted by Dasatinib due to bradycardia associated with Ponatinib...During the second consolidation cycle, Bosutinib was introduced with good tolerance... An allo-HSCT from an HLA-matched sibling was performed in August 2023, conditioning with TBF regimen (Thiothepa, Busulfan, and Fludarabine) and Cyclosporine and Methotrexate in a short-course regimen as prophylaxis for graft-versus-host disease (GVHD)...Donor lymphocyte infusion (DLI) was initiated.After two DLIs, the patient..."

Clinical • Bone Marrow Transplantation • Cardiovascular • Chronic Myeloid Leukemia • Endocrine Disorders • Fatigue • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Malignancies • Hepatology • Immunology • Leukemia • Musculoskeletal Pain • Oncology • Pain • Transplantation • ABL1

How I treat chronic myeloid leukemia in children and adolescents. (PubMed, Blood) - "Following the initial approval of first-generation imatinib for pediatric CML in 2003, three TKIs, all second-generation TKIs (2G-TKIs), have been approved, including dasatinib, nilotinib and bosutinib, which has greatly expanded therapeutic options but also added complexity to treatment determination. The expanded treatment options also call into question the treatment choice for pediatric CML, long-term efficacy and safety profiles of these TKIs. We present three cases commonly encountered in pediatric CML, their challenges and relevant issues as well as recommended managements."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics

Oncogenic and immunological functions of USP35 in pan-cancer and its potential as a biomarker in kidney clear cell carcinoma. (PubMed, BMC Cancer) - "USP35 is overexpressed in KIRC and associated with poor prognosis, likely promoting tumor progression through oncogenic pathways and immune modulation. Its correlation with drug sensitivity positions USP35 as a potential therapeutic target, warranting further investigation into its mechanistic functions and therapeutic applications."

Biomarker • Journal • Pan tumor • Clear Cell Carcinoma • Immune Modulation • Immunology • Oncology • Renal Cell Carcinoma • Targeted Protein Degradation

DASATINIB INDUCED PULMONARY ARTERIAL HYPERTENSION - Jennifer Drummond (ACC 2025) - "Treatment with bumetanide and sildenafil was initiated...PAH may recur in patients treated with bosutinib following DS induced PAH, possibly due to priming effects of Src kinase inhibition by DS... PAH is a rare but important to recognize adverse effect of DS. Effusions are common (15-30 %) and do not always require treatment cessation. Baseline echocardiogram is recommended but optimal surveillance strategy requires further investigation."

Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Cardiovascular • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • Pulmonary Arterial Hypertension • Respiratory Diseases • ABL1 • BCR

TKO (TOTAL KNOCK OUT) BY TKI (TYROSINE KINASE INHIBITOR) - Roudabeh Kiani (ACC 2025) - "Clinicians should be mindful of these medications as potential causes of QT prolongation or other cardiovascular conditions, even though such side effects are rare."

Cardiovascular • Chronic Myeloid Leukemia • CNS Disorders • Epilepsy • Gastrointestinal Disorder • Hematological Malignancies • Leukemia • Oncology • Ventricular Tachycardia • ABL1 • BCR

CHALLENGING THE GUIDELINES ON TYROSINE KINASE INHIBITOR INITIATION WITH CONCOMITANT USE OF ANTIARRHYTHMIC DRUGS - Shyla McMurtry (ACC 2025) - "With close EKG monitoring and dose adjustment of antiarrhythmics, we demonstrate that antiarrhythmic use should not dissuade TKI initiation. As permissive cardiotoxicity gains traction in cardio-oncology underlying risk factors, EKG and laboratory data must be considered."

Cardiovascular • Chronic Myeloid Leukemia • Heart Failure • Hematological Malignancies • Leukemia • Oncology

RECURRENT BOSUTINIB-INDUCED PERICARDIAL EFFUSION IN CML - Puneet Razdan (ACC 2025) - "Awareness of bosutinib's cardiac risks needs to be raised. Questions remain, such as should these patients should switch to alternate agents or lower the dosage of bosutinib. More research is needed to understand severe reactions and future options going forward."

Cardiovascular • Chronic Myeloid Leukemia • Infectious Disease

Construction of a novel prognostic model based on lncRNAs-related to DNA damage repair for predicting the prognosis of clear cell renal cell carcinoma. (PubMed, Ann Med) - "In addition, it was found that the high and low risk groups had different sensitivities to the drugs Etoposide, Imatinib, Sorafenib, Bosutinib and Sunitinib. A novel prognostic model was constructed based on four DElncRNAs-related to DDR. The model has satisfactory accuracy in predicting survival of ccRCC patients."

Biomarker • Journal • Tumor mutational burden • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • CD8 • PBRM1 • TMB

Bosulif - opinion on variation to marketing authorisation (European Medicines Agency) - "On 27 March 2025, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending a change to the terms of the marketing authorisation for the medicinal product Bosulif. The marketing authorisation holder for this medicinal product is Pfizer Europe MA EEIG. The CHMP adopted a change to the existing indications to extend the use of Bosulif to children aged 6 years and older with certain types of chronic myelogenous leukaemia, along with a new pharmaceutical form, hard capsules, associated with two new strengths, 50 mg and 100 mg."

CHMP • Chronic Myeloid Leukemia

Asciminib: the tyrosine kinase inhibitor with a unique mechanism of action. (PubMed, Expert Opin Pharmacother) - "Imatinib (first generation), dasatinib, nilotinib and bosutinib (second generation) and ponatinib (third generation) are the five approved TKIs that inhibit BCR::ABL1 by binding to the ATP binding site of ABL1. In this review we detail the mechanism of action, preclinical data, clinical data, safety and tolerability of asciminib. Due to its mechanism of action, asciminib has fewer off target effects, resulting in an improved safety and tolerability profile."

Journal • Review • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Chronic Myeloid Leukemia: A Review. (PubMed, JAMA) - "Six BCR::ABL1 TKIs have been approved by the US Food and Drug Administration, including 5 that are first-line treatment (imatinib, dasatinib, bosutinib, nilotinib, and asciminib) and 5 approved for treatment after disease progression despite initial therapy (dasatinib, bosutinib, nilotinib, ponatinib, asciminib). Many patients require continuous TKI therapy. Therefore, TKI therapy should be selected with consideration of adverse effects, and patients should be helped to maximize adherence to TKI treatment."

Journal • Bone Marrow Transplantation • Cardiovascular • Chronic Myeloid Leukemia • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • Myocardial Infarction • Oncology • Pancreatitis • Peripheral Arterial Disease • Respiratory Diseases • Transplantation • ABL1

Clinical trial of bosutinib for amyotrophic lateral sclerosis: iDReAM study (JSNE 2025) - No abstract available

Clinical • Amyotrophic Lateral Sclerosis • CNS Disorders

“Extension application to introduce a new pharmaceutical form associated with two new strengths (50 mg and 100 mg) grouped with an extension of indication to include treatment of pediatric patients greater than or equal to 1 year of age with newly-diagnosed chronic phase Philadelphia chromosome positive CML…based on...(BCHILD)...sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated.” (European Medicines Agency) - Pharmacovigilance Risk Assessment Committee (PRAC)-Draft agenda for the meeting on 10 - 13 Mar 2025: “For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP”

PRAC • Chronic Myeloid Leukemia • Hematological Malignancies • Oncology