Moreover, combination of dasatinib with BTK inhibitors (BTKi) (ibrutinib, acalabrutinib or zanubrutinib) significantly decreased E2A-PBX1+/preBCR+ human and murine cell proliferation, reduced PLCG2 and BTK phosphorylation and total protein levels and increased disease-free survival of mice in secondary transplantation assays, reducing particularly CNS-leukemic infiltration. Hence, dasatinib with ibrutinib reduced pPLCG2 and pBTK in primary ALL patient samples, including E2A-PBX1+ ALLs. In summary, genetic depletion and pharmacological inhibition of BTK increase dasatinib effects in human and mouse E2A-PBX1+/preBCR+ ALL in most of performed assays, and the combination of dasatinib and BTKi is very effective in reducing CNS-infiltration of E2A-PBX1+/preBCR+ ALL cells in vivo.

P2, N=10, Not yet recruiting, Fudan University

Although 3 µM dasatinib reduced 100 µM OHP accumulation in hOCT2-HEK293 cells, co-incubation with dasatinib and OHP did not prevent OHP toxicity, possibly due to dasatinib-induced cell viability reduction. In summary, this study demonstrates OHP as an OCT2 substrate and dasatinib as a non-transported inhibitor and regulator of OCT2, offering potential for OIPN mitigation.

The development of chronic myeloid leukaemia (CML) subsequent to chronic lymphocytic leukaemia (CLL) is an uncommon occurrence, challenging conventional expectations of disease evolution in chronic leukaemia.Extensive and appropriate testing is necessary to promptly identify secondary CML in CLL patients.Targeted therapy with dasatinib, a tyrosine kinase inhibitor, may demonstrate efficacy in reducing leukocytosis and BCR-ABL1 levels in patients with coexisting CLL and CML.

Of these drugs, dasatinib was significant in both methods and might be considered a potential novel drug for treating high-risk GC patients...We created a novel APOBEC3-related LPS in predicting the prognosis with regards to individual GC patients. Importantly, this APOBEC3-related LPS was closely associated with immunity and might guide clinical treatment.

The xenograft mouse model suggested that the combination was more efficient and safer. In short, CBD and low-dose dasatinib exhibited a synergistic effect on anticancer by targeting the SRC/PI3K/AKT signaling pathway, suggesting a potential therapeutic option for the treatment of lung cancer.

No abstract available

Chylothorax is a lymphatic chylous pleural effusion typically associated with traumatic (iatrogenic, non-iatrogenic) and non-traumatic (infections, malignancy, lymphatic disorders) aetiologies. Drug-induced chylothorax is uncommon and mostly reported in association with BCR-ABL tyrosine kinase inhibitor therapy.

The GNC co-loaded dasatinib, a CAF inhibitor, and paclitaxel, a chemotherapeutic agent, to deactivate CAFs and enhance the effects of immunogenic chemotherapy. Moreover, GNC treatment exhibited remarkable immunostimulatory efficacy, including CD8+ T cell expansion and PD-L1 downregulation, facilitating immune checkpoint blockade therapy. In summary, the integration of CAF deactivation and immunogenic chemotherapy using the GNC nanoplatform holds promise for rebuilding immune-excluded tumors.

P1, N=19, Active, not recruiting, National Cancer Institute (NCI)

P2, N=406, Active, not recruiting, National Cancer Institute (NCI) | Phase classification: P2b --> P2

ETV6::ABL1 is a rare but recurrent genetic aberration in AML, and the combined use of fluorescence in situ hybridization and PCR can better identify this fusion gene. Patients carrying ETV6::ABL1 have a high relapse rate and a poor prognosis. TKIs are a reasonable treatment option for this group, and allo-HSCT may be curative.

Finally, the subpopulation-enriched targets and drugs were confirmed through ConnectivityMap (CMAP) analysis and multi-omics, respectively. In this study, positive samples for CXCL13, EPSTI1, and CDK1 exhibited poor prognostic significance in treatment-naïve LUAD cases but demonstrated benefits from PD-L1 blockade and dasatinib therapies.

Additionally, we found that patients with a high PCDI score may exhibit resistance to immunotherapy and standard adjuvant chemotherapy regimens; however, they may benefit from other FDA-supported drugs such as docetaxel and dasatinib. In conclusion, the PCDI holds potential as a prognostic signature and can facilitate personalized treatment for LUAD patients.

HDAC5 was upregulated by dasatinib and erlotinib in the majority of the cell lines. HDAC5 was not upregulated in the UACC-257 cell line resistant to dasatinib. The effects of cancer drug treatment on expression of HDAC and SIRT genes may influence chemosensitivity and may need to be considered during chemotherapy.

P3, N=204, Completed, University of Ulm | Active, not recruiting --> Completed

Concurrent use of naringenin-containing supplements, herbs, or foods with dasatinib may cause serious and potentially life-threatening drug interactions. Further studies are necessary to determine the clinical significance of these findings.

We find that the overexpression of targeting protein for Xklp2 (TPX2) enhances sensitivity to the proto-oncogene c-Src (SRC) inhibitor dasatinib due to activation of the Yes-associated protein 1 (YAP) pathway. Furthermore, using breast cancer data from The Cancer Genome Atlas (TCGA) and a cohort of cancer-derived patient samples, we find that both TPX2 overexpression and YAP activation are present in a significant percentage of cancer tumor samples and are associated with poor prognosis; therefore, they are putative biomarkers for selection for dasatinib therapy.

Collectively, the heterogeneity of phosphorylation exists in different molecular subtypes of breast cancer. PRKCD_pY313 activates Src and accelerates TNBC progression, which could be inhibited by Dasatinib.

Our study has unveiled a newfound fusion gene, TERF2::PDGFRB, and we have found that patients carrying this fusion gene exhibit sensitivity to dasatinib. When transfused into mice, Ba/F3 cells with the TERF2::PDGFRB fusion gene induce tumorigenesis and a shortened lifespan in cell-derived graft models, but this outcome can be improved with imatinib treatment. In summary, we have identified the novel TERF2::PDGFRB fusion gene, which exhibits oncogenic potential both in vitro and in vivo, making it a potential therapeutic target for tyrosine kinase inhibitors (TKIs).

P2, N=107, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed

Out of 44 known ADME proteins in plasma EVs, previously annotated mouse cytochrome P450 3A11 (Cyp3a11), homolog to human CYP3A4, and uridine 5'-diphospho (UDP) glucuronosyltransferase 2A3 (Ugt2a3), increased upon daily rifampicin dosage. Dasatinib, a tyrosine kinase inhibitor to treat leukemia, also elevated Cyp3a11 levels in plasma EVs, but to a lesser extent. Altogether, this study demonstrates that measuring drug enzymes in circulating EVs as an effective surrogate is highly feasible and may transform today's drug discovery and development for personalized medicine.

P2/3, N=160, Recruiting, Cedars-Sinai Medical Center | Not yet recruiting --> Recruiting

TBX1 forms an integral part of an oncogenic regulatory network impacting proliferation, survival, and differentiation. Thus, the data spotlight novel diagnostic markers and potential therapeutic targets for this malignancy.

Transmission electron microscopy demonstrated that dasatinib treatment increased cell membrane protrusion contacts and generated spaces between cells, which may allow epidermal growth factor receptor activity at the cell-cell contacts. This study suggests that dasatinib treatment does not inhibit cell survival but targets Src at different cellular compartments in the coordination of focal adhesions and cell-cell contacts in collective cell migration through E-cadherin dynamics in colon cancer cells.

P1/2, N=1, Terminated, National Cancer Institute (NCI) | N=18 --> 1 | Trial completion date: Jun 2026 --> Dec 2023 | Recruiting --> Terminated | Trial primary completion date: Jun 2026 --> Dec 2023; Other - Poor accrual

In the present study, we found that DMC treatment selectively eliminated senescent cells, and DMC alone or a combination of DMC and quercetin or dasatinib showed high efficiency in the clearance of senescent cells...Importantly, we found that DMC treatment prevented hair loss, improved motor coordination, and reduced the expression of several senescence-associated secretory phenotype factors (IL-6, IL-1β, CXCL-10, and MMP12) in the liver of old mice. Collectively, we revealed that, through the induction of ferroptosis, DMC holds the promise as a new senolytics to prevent age-related pathologies.

Patients in the high-risk group were more sensitive to bicalutamide, gefitinib, and dasatinib; patients in the low-risk group were associated with poor response to immunotherapy. The validation of the six genes in the prognostic model was consistent with the results of bioinformatics analysis. The NETs-based prognostic model and nomogram proposed in this study are promising prognostic prediction tools for GBM, which may provide new ideas for the development of precise tumour targeted therapy.

In vivo studies showed that compound 7s exhibited stronger antitumor activity compared to dasatinib, without causing significant weight loss at a dose of 30 mg/kg. In vivo experiments confirmed that compound 7s, at a dose of 30 mg/kg, effectively inhibited DDR1 activation, resulting in a reduction of lung injury and fibrosis induced by bleomycin. Overall, these findings highlight the potential of these novel DDR1 inhibitors as promising therapeutic candidates for the treatment of DDR-related diseases.

Because the thiazole ring is present in dasatinib, which is currently used in anticancer therapy, it is important to highlight the ring...The most effective inhibitory compounds were further tested in vitro against both epidermal growth factor receptor (EGFR) and B-Raf proto-oncogene, serine/threonine kinase (BRAF) targets. Additionally, molecular docking analysis examined how these molecules bind to the active sites of EGFR and BRAF.

Using dasatinib linked to E3 ligase ligands, we identified a potent and selective dual Csk/c-Src PROTAC degrader...We demonstrated a high degree of catalysis with our c-Src PROTACs. Using our c-Src PROTACs, we identified pharmacological advantages of c-Src degradation compared to inhibition with respect to cancer cell proliferation.

P2, N=48, Recruiting, Wake Forest University Health Sciences | Trial completion date: Jan 2032 --> Jan 2026 | Trial primary completion date: Jan 2027 --> Jan 2025

P2, N=60, Recruiting, Fundació Institut Germans Trias i Pujol | Not yet recruiting --> Recruiting | Initiation date: Jul 2023 --> Oct 2023

Dasatinib is potential to hinder the spontaneous progression from preinvasive to invasive lesion of lung adenocarcinoma. Together, plasmatic lncCRLA is defined as a brand-new circulating biomarker to predict the occurrence and evolvement of lung adenocarcinoma, a light for early detection of lung adenocarcinoma.

We also found that EphA2 can form liquid-liquid phase separation condensates on cell membrane, which can be disrupted by ALW-II-41-27, an inhibitor of EphA2. In addition, we found that EphA2 expression in colorectal cancer was positively correlated with the expression of ferroptosis-related genes and the infiltration of multiple immune cells. These findings suggest that EphA2 is a novel membrane protein with phase separation ability and is associated with ferroptosis and immune cell infiltration, which further suggests that malignant progression of colorectal cancer may be inhibited by suppressing the phase separation ability of EphA2.

The relative migration and invasion abilities of erlotinib-resistant PC9 (PC9/ER) and gefitinib-resistant PC9 (PC9/GR) cells were higher than those of parental PC9 cells...Dasatinib downregulated N-cadherin, Twist, and vimentin, suggesting that Src regulates EMT in resistant cells. Notably, CuB played a key role in mediating the anti-metastatic activity of ETK. Collectively, our results demonstrate that ETK can attenuate the metastatic ability of EGFR-TKI-resistant lung cancer cells by inhibiting Src-mediated EMT.

TKIs with better CNS activity such as dasatinib might be preferred over imatinib. The underlying reasons for the notable outcome disparity between Western and Asian patients are unclear and warrant further investigation. Furthermore, our study underscores the importance of IHC in cases where low-level LBs are detected by FC, given the significant underestimation of LBs by FC.

All there patients received the same IA regimen(idarubicincytarabine) as induction chemotherapy and achieved complete remission, followed by multi-agent chemotherapy as consolidation treatment...1 received additional targeted therapy with sorafenib... ETV6-ABL1 fusion gene is a rare but recurrent genetic aberration in AML, and its rearrangement is not uniform across eachpatient, typically involving cryptic insertions. Routine chromosome G-banding analysis may not identify this fusion gene, and the combined use of fluorescence in situ hybridization and PCR is recommended for better detection for ETV6-ABL1. Patients with this fusion gene have a high relapse rate and a poor prognosis.

Non-hematological toxicity occurred in one patient (20%) with nausea and galactorrhea due to ketoconazole...The CYP inhibition strategy can decrease the cost of dasatinib to a point where it is cheaper than full-dose imatinib -the cheapest TKI- and represent a treatment option for patients who cannot afford full-dose dasatinib in low income countries...3-$100. 8 monthly

Dasatinib is the preferred TKI, followed by imatinib. There was a high degree of treatment abandonment, with an 18% loss from follow-up within six months (including 12% during the induction phase).

Risk factor analysis for the TFR2 after dasatinib discontinuation suggested three significant factors: (1) doubling time of BCR::ABL1 transcript following TFR1 attempt, (2) rapid regaining of molecular response following dasatinib therapy and (3) undetectable BCR::ABL1 transcript prior to TFR2 attempt. The present study showed that dasatinib does not increase the TFR2 rate in general, but a selected group of patients could benefit from this approach.

P1, N=15, Recruiting, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Mar 2024 --> Mar 2025