^
16d
Exploration on the construction of a bladder cancer prognostic model based on disulfidptosis-related lncRNAs and its clinical significance. (PubMed, Sci Rep)
Lastly, the drug sensitivity analysis revealed that the BLCA cells in the high-risk group showed an increased sensitivity to cisplatin, sunitinib, cetuximab, axitinib, docetaxel, saracatinib, vinblastine and pazopanib compared with those in the low-risk group. According to the Quantitative real time PCR results, we found that five lncRNAs of the risk model were more highly expressed in BCa cell lines than human immortalized uroepithelial cell line. The disulfidptosis-related lncRNA risk model has a valuable effect in assessing the prognosis of BLCA patients.
Journal • Tumor mutational burden • IO biomarker
|
TMB (Tumor Mutational Burden)
|
TMB-L
|
Erbitux (cetuximab) • cisplatin • docetaxel • sunitinib • pazopanib • Inlyta (axitinib) • saracatinib (AZD0530) • vinblastine
26d
A Multi-Omics Prognostic Model Capturing Tumor Stemness and the Immune Microenvironment in Clear Cell Renal Cell Carcinoma. (PubMed, Biomedicines)
The CRCS2 subtype was in a hypoxic state and was characterized by suppression and exclusion of immune function, which was sensitive to gefitinib, erlotinib, and saracatinib. Our findings highlight the key role of CSCs in shaping the ccRCC tumor microenvironment, crucial for therapy research and clinical guidance. Recognizing tumor stemness helps to predict treatment efficacy, recurrence, and drug resistance, informing treatment strategies and enhancing ccRCC patient outcomes.
Journal
|
SAA2 (Serum Amyloid A2)
|
erlotinib • gefitinib • saracatinib (AZD0530)
3ms
Construction of a prognostic model for colon cancer by combining endoplasmic reticulum stress responsive genes. (PubMed)
Finally, based on the cMAP database, we identified several potential drugs that could target high-risk groups, such as Dasatinib, GNF-2, Saracatinib, and WZ-1-84. This model can be used as a predictor of prognosis and immunotherapy response in colon cancer patients. At the same time, model-based prediction of drugs can also be a potential option for colon cancer treatment in the future.
Journal • IO biomarker
|
Oncotype DX® Colon Recurrence Score test
|
dasatinib • saracatinib (AZD0530)
5ms
EGFRvIII Confers Sensitivity to Saracatinib in a STAT5-Dependent Manner in Glioblastoma. (PubMed, Int J Mol Sci)
Our findings reveal that exogenous expression of paralogs STAT5A and STAT5B augments cell proliferation and that inhibition of STAT5 phosphorylation in vivo improves overall survival in combination with temozolomide (TMZ). Constitutively active STAT5A or STAT5B mitigates saracatinib sensitivity in EGFRvIII+ cells. In vivo, saracatinib treatment decreased survival in mice bearing EGFR WT tumors compared to the control, yet in EGFRvIII+ tumors, treatment with saracatinib in combination with TMZ preferentially improves survival.
Journal
|
JAK1 (Janus Kinase 1) • STAT5B (Signal Transducer And Activator Of Transcription 5B) • STAT5A (Signal Transducer And Activator Of Transcription 5A)
|
temozolomide • saracatinib (AZD0530)
6ms
Identification of a Macrophage marker gene signature to evaluate immune infiltration and therapeutic response in hepatocellular carcinoma. (PubMed, Heliyon)
Moreover, a low-Macrosig score indicates increased sensitivity to AZD.2281, A.443654, ABT.263, ABT.888, AG.014699 and ATRA, while a high Macrosig score indicates increased sensitivity to AZD6482, AKT inhibitor VIII, AS601245, AZ628, AZD.0530 and AZD6244. A novel scoring system was constructed to guide more effective prognostic evaluation and tailoring therapeutic regimens for HCC patients.
Journal • Gene Signature • PD(L)-1 Biomarker • IO biomarker
|
PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2)
|
Lynparza (olaparib) • Koselugo (selumetinib) • Rubraca (rucaparib) • veliparib (ABT-888) • navitoclax (ABT 263) • AZ 628 • saracatinib (AZD0530) • AZD6482 • A 443654
7ms
STOPFOP: Saracatinib Trial TO Prevent FOP (clinicaltrials.gov)
P2, N=20, Recruiting, Amsterdam UMC, location VUmc | Trial completion date: Aug 2024 --> May 2025 | Trial primary completion date: Aug 2024 --> May 2025
Trial completion date • Trial primary completion date
|
ACVR1 R206H
|
saracatinib (AZD0530)
7ms
STOP-IPF: Saracatinib in the Treatment of Idiopathic Pulmonary Fibrosis (clinicaltrials.gov)
P1/2, N=49, Active, not recruiting, National Jewish Health | Recruiting --> Active, not recruiting
Enrollment closed
|
saracatinib (AZD0530)
7ms
Proteogenomic Characterization Reveals Estrogen Signaling as a Target for Never-Smoker Lung Adenocarcinoma Patients without EGFR or ALK Alterations. (PubMed, Cancer Res)
Collectively, this study enhanced our understanding of NENA NSLA by elucidating the proteogenomic landscape and proposed saracatinib as a potential treatment for this patient population that lacks effective targeted therapies. The proteogenomic landscape in never-smoker lung cancer without known driver mutations reveals prognostic proteins and enhanced estrogen signaling that can be targeted as a potential therapeutic strategy to improve patient outcomes.
Journal
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MSI (Microsatellite instability) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • STK11 (Serine/threonine kinase 11) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • LLGL2 (LLGL Scribble Cell Polarity Complex Component 2) • ST14 (ST14 transmembrane serine protease matriptase)
|
STK11 mutation • ALK fusion • ROS1 fusion • SETD2 mutation
|
saracatinib (AZD0530)
8ms
STOP-IPF: Saracatinib in the Treatment of Idiopathic Pulmonary Fibrosis (clinicaltrials.gov)
P1/2, N=49, Recruiting, National Jewish Health | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Dec 2023 --> Sep 2024
Trial completion date • Trial primary completion date
|
saracatinib (AZD0530)
9ms
Saracatinib inhibits necroptosis and ameliorates psoriatic inflammation by targeting MLKL. (PubMed, Cell Death Dis)
In an imiquimod (IMQ)-induced psoriasis mouse model, saracatinib effectively blocked MLKL phosphorylation and inflammatory responses in vivo. Taken together, these findings indicate that saracatinib inhibits necroptosis by targeting MLKL, providing a potential therapeutic approach for skin inflammation-related diseases such as psoriasis.
Journal
|
RIPK1 (Receptor Interacting Serine/Threonine Kinase 1)
|
saracatinib (AZD0530) • Zyclara (imiquimod)
11ms
A novel prognostic and therapeutic target biomarker based on complement-related gene signature in gastric cancer. (PubMed, Transl Cancer Res)
Besides, compared to the low-risk group, there were higher expressions of most immune checkpoint genes and HLA genes in the high-risk group, and the high-risk patients showed higher sensitivity to the chemotherapy and targeted drugs (axitinib, dasatinib, pazopanib, saracatinib, sunitinib and temsirolimus). The novel CRG signature may act as a reliable, efficient tool for prognostic prediction and treatment guidance in future clinical practice.
Journal • Gene Signature • IO biomarker
|
CD36 (thrombospondin receptor) • SERPINE1 (Serpin Family E Member 1)
|
dasatinib • sunitinib • pazopanib • Torisel (temsirolimus) • Inlyta (axitinib) • saracatinib (AZD0530)
11ms
Characterization of gastric cancer-stimulated signaling pathways and function of CTGF in cancer-associated fibroblasts. (PubMed, Cell Commun Signal)
This study provides a characterization of the signaling pathways and effector genes involved in CAFs activation, and strategies that could effectively inhibit it in the context of GC. Video Abstract.
Journal
|
CDH1 (Cadherin 1) • STAT3 (Signal Transducer And Activator Of Transcription 3) • TJP1 (Tight Junction Protein 1) • CTGF (Connective tissue growth factor)
|
CDH1 expression
|
dasatinib • saracatinib (AZD0530)
11ms
Construction of a prognostic model for lung adenocarcinoma based on m6A/m5C/m1A genes. (PubMed, Hum Mol Genet)
Based on the m6A/m5C/m1A-related genes in LUAD, LUAD patients were divided into 2 subtypes, and a m6A/m5C/m1A-related LUAD prognostic model was constructed to provide a reference for the prognosis prediction of LUAD.
Journal
|
CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
|
Alecensa (alectinib) • Alunbrig (brigatinib) • irinotecan • Torisel (temsirolimus) • saracatinib (AZD0530) • elesclomol (STA-4783) • Emcyt (estramustine)
12ms
Overcoming BCR::ABL1 dependent and independent survival mechanisms in chronic myeloid leukaemia using a multi-kinase targeting approach. (PubMed, Cell Commun Signal)
BMP signalling pathway is important for CML cell survival. Targeting SRC, ABL and ALK kinases is more effective than ABL inhibition alone, the combination efficacy importantly being demonstrated in both 2D and 3D cell cultures highlighting the need for combinatorial therapies in contrast to standard of care single agents. Our study provides justification to target multiple kinases in CML to combat LSC persistence.
Journal
|
ABL1 (ABL proto-oncogene 1) • CD34 (CD34 molecule) • BMP4 (Bone Morphogenetic Protein 4)
|
imatinib • saracatinib (AZD0530) • dorsomorphin (Compound C)
12ms
Prognostic value analysis of cholesterol and cholesterol homeostasis related genes in breast cancer by Mendelian randomization and multi-omics machine learning. (PubMed, Front Oncol)
It can also optimize the administration of various first-line drugs, including AKT inhibitors VIII Imatinib, Crizotinib, Saracatinib, Erlotinib, Dasatinib, Rapamycin, Roscovitine and Shikonin in BC patients. Finally, we employed machine learning techniques to construct a multi-omics prediction model(Risklight),with an area under the feature curve (AUC) of up to 0.89. With the help of CAG_score and Risklight, we reveal the signature of cholesterol homeostasis-related genes for angiogenesis, immune responses, and the therapeutic response in breast cancer, which contributes to precision medicine and improved prognosis of BC.
Journal • Machine learning
|
CDH5 (Cadherin 5) • CLDN5 (Claudin 5)
|
Xalkori (crizotinib) • erlotinib • dasatinib • imatinib • sirolimus • saracatinib (AZD0530) • seliciclib (CYC202)
almost1year
A multi-omic investigation of lung adenocarcinoma molecular subtypes. (PubMed, J Chin Med Assoc)
This study introduced an innovative multiomics data analysis pipeline. Using this approach, we successfully identified 4 molecular subtypes of lung adenocarcinoma as well as their candidate therapeutic agents. The newly identified subtypes can be combined with the current biomarkers to generate a comprehensive roadmap for treatment decision-making.
Journal
|
KRAS (KRAS proto-oncogene GTPase) • TGFB1 (Transforming Growth Factor Beta 1) • EIF4G1 (Eukaryotic translation initiation factor 4 gamma, 1)
|
everolimus • saracatinib (AZD0530)
1year
Immunotherapy and Targeted Therapies Efficacy in Thymic Epithelial Tumors: A Systematic Review. (PubMed, Biomedicines)
Despite study heterogeneity, this review shows that ICI could be a therapeutic option for selected patients with TET that are not amenable to curative radical treatment after first-line chemotherapy.
Review • Journal • Tumor mutational burden • IO biomarker
|
TMB (Tumor Mutational Burden) • CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • MSR1 (Macrophage Scavenger Receptor 1)
|
Avastin (bevacizumab) • erlotinib • imatinib • Lenvima (lenvatinib) • saracatinib (AZD0530)
1year
Understanding cancer drug resistance with Sleeping Beauty functional genomic screens: Application to MAPK inhibition in cutaneous melanoma. (PubMed, iScience)
To target this mechanism, we showed that an inhibitor of SRC, saracatinib, blunts the VAV1-induced transcriptional reprogramming. Overall, we highlighted the importance of accounting for melanoma heterogeneity in treating cutaneous melanoma with MAPK inhibitors. Moreover, we demonstrated the utility of the Sleeping Beauty transposon system in understanding cancer drug resistance.
Journal
|
RAC1 (Rac Family Small GTPase 1) • VAV1 (Vav Guanine Nucleotide Exchange Factor 1)
|
BRAF mutation
|
saracatinib (AZD0530)
1year
POLD4 Promotes Glioma Cell Proliferation and Suppressive Immune Microenvironment: A Pan-Cancer Analysis Integrated with Experimental Validation. (PubMed, Int J Mol Sci)
Drugs like trametinib, saracatinib, and dasatinib may be used in patients with high POLD4. Using experimental analysis, we further confirmed the overexpression of POLD4 in gliomas, as well as its correlation with glioma recurrence, proliferation, and the suppressive immune microenvironment. Our research findings indicate that the expression pattern of POLD4 not only serves as a robust indicator of prognosis in cancer patients but also holds promising potential as a new focus for treatment.
Journal • IO biomarker • Pan tumor
|
KEAP1 (Kelch Like ECH Associated Protein 1) • POLD1 (DNA Polymerase Delta 1)
|
Mekinist (trametinib) • dasatinib • saracatinib (AZD0530)
1year
Inhibition of ErbB3 and Associated Regulatory Pathways Potently Impairs Malignant Peripheral Nerve Sheath Tumor Proliferation and Survival. (PubMed, Am J Pathol)
ErbB inhibitors (canertinib and sapitinib) or erbB3 knockdown in combination with Src (saracatinib), calmodulin [trifluoperazine (TFP)], or proviral integration site of Moloney murine leukemia kinase (AZD1208) inhibition even more effectively reduces proliferation and survival. Src inhibition (saracatinib), like erbB3 knockdown, prevents these phosphorylation events and when combined with trifluoperazine even more effectively reduces proliferation and survival compared to monotherapy. Our findings implicate erbB3, calmodulin, PIM kinases and Src family members as important therapeutic targets in MPNSTs and demonstrate that combinatorial therapies targeting critical MPNST signaling pathways are more effective.
Journal
|
ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1)
|
saracatinib (AZD0530) • AZD1208 • canertinib (CI-1033) • sapitinib (AZD8931)
over1year
Identification of Macrophage Associated Gene Landscape to Evaluate Immune Infiltration and Therapeutic Response in Hepatocellular Carcinoma (APPLE 2023)
A novel scoring system based on macrophage subclusters was constructed, thereby guiding more effective prognostic evaluation and tailored potential drug agents strategies of HCC patients.
PD(L)-1 Biomarker • IO biomarker
|
PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2)
|
Lynparza (olaparib) • Koselugo (selumetinib) • Rubraca (rucaparib) • veliparib (ABT-888) • navitoclax (ABT 263) • AZ 628 • saracatinib (AZD0530) • AZD6482 • A 443654
over1year
Identification of novel stemness-based subtypes and construction of a prognostic risk model for patients with lung squamous cell carcinoma. (PubMed, Curr Stem Cell Res Ther)
The stemness-based subtypes shed novel insights into the potential roles of LUSC-stemness in tumor heterogeneity, and our prognostic signatures offer a promising tool for prognosis prediction and guide therapeutic decisions in LUSC.
Journal • IO biomarker
|
TP53 (Tumor protein P53) • TTN (Titin) • BMI1 (BMI1 proto-oncogene, polycomb ring finger) • EIF1AX (Eukaryotic Translation Initiation Factor 1A X-Linked) • FAM43A (Family With Sequence Similarity 43 Member A)
|
TP53 mutation • TTN mutation
|
dasatinib • paclitaxel • imatinib • sunitinib • saracatinib (AZD0530)
over1year
Saracatinib synergizes with enzalutamide to downregulate AR activity in CRPC. (PubMed, Front Oncol)
Second generation hormonal therapies such as abiraterone acetate and enzalutamide are typically given to men with CRPC. Lastly, we also found that the saracatinib-enzalutamide combination reduced DNA replication compared to the saracatinib-docetaxel combination, resulting in marked increased apoptosis. By elucidating this combination strategy, we provide pre-clinical data that suggests combining SRC kinase inhibitors with enzalutamide in select patients that express both AR-FL and AR-Vs.
Journal
|
AR (Androgen receptor)
|
AR mutation • AR amplification • AR expression
|
docetaxel • Xtandi (enzalutamide capsule) • abiraterone acetate • saracatinib (AZD0530)
over1year
Activated Src kinases downstream of BCR-ABL and Flt3 induces proteasomal degradation of SHIP1 by phosphorylation of tyrosine 1021. (PubMed, Biochim Biophys Acta Mol Cell Res)
Inhibition of BCR-ABL (Imatinib), Flt3 (Quizartinib) or Src-Kinase-Family (Saracatinib) leads to significant reconstitution of SHIP1 protein expression. These results further support a functional role of SHIP1 as tumor suppressor protein and could be the basis for the establishment of a targeted therapy form.
Journal
|
FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • KMT2A (Lysine Methyltransferase 2A) • INPP5D (Inositol Polyphosphate-5-Phosphatase D)
|
MLL translocation
|
imatinib • Vanflyta (quizartinib) • saracatinib (AZD0530)
over1year
Treatment for ovarian clear cell carcinoma with combined inhibition of WEE1 and ATR. (PubMed, J Ovarian Res)
In a selection of 166 compounds we showed that inhibitors of ATR and WEE1 were cytotoxic against a panel of OCCC cell lines. These two drugs are already in other clinical trials, making them ideal candidates for treatment of OCCC.
Journal
|
ARID1A (AT-rich interaction domain 1A)
|
ARID1A mutation
|
adavosertib (AZD1775) • pictilisib (GDC-0941) • ceralasertib (AZD6738) • idasanutlin (RG7388) • saracatinib (AZD0530) • torkinib (PP242) • AZD4320
over1year
The potential of combined treatments between Src tyrosine kinase inhibitors and sorafenib in heterogeneous liver cancer cells (LCS 2023)
All cell lines were treated with Src inhibitors, saracatinib (SAR) and dasatinib (DAS), with concentration ranging from 0.02 to 10.00 µM. Src tyrosine kinase inhibitors combined with SOR therapy may provide a potential treatment advantage in HCC to comprise cellular heterogeneity.
TGFB1 (Transforming Growth Factor Beta 1)
|
dasatinib • sorafenib • saracatinib (AZD0530)
over1year
Chemokine (C-C motif) Ligand 2 Is Regulated Through the EGFR/Src Pathway in HER2-positive Breast Cancer Cells. (PubMed, Anticancer Res)
CCL2 expression is regulated through the EGFR/Src-dependent signaling in HER2+ breast cancer.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • CCL2 (Chemokine (C-C motif) ligand 2)
|
HER-2 positive • HER-2 overexpression
|
Herceptin (trastuzumab) • Nerlynx (neratinib) • saracatinib (AZD0530)
almost2years
Plasminogen activator, urokinase enhances the migration, invasion, and proliferation of colorectal cancer cells by activating the Src/ERK pathway. (PubMed, J Gastrointest Oncol)
After being treated with saracatinib, we observed significantly decreased protein levels of p-ERK, matrix metallopeptidase 2 (MMP-2), MMP-3, MMP-9, Cyclin D1, and Cyclin A2 in the SW480 cells. In conclusion, PLAU affects the migration, invasion, and proliferation of CRC cells by activating the Src/ERK pathway.
Journal
|
CCND1 (Cyclin D1) • MMP2 (Matrix metallopeptidase 2) • CCNA2 (Cyclin A2) • MMP9 (Matrix metallopeptidase 9) • MMP3 (Matrix metallopeptidase 3) • PLAU (Plasminogen Activator)
|
saracatinib (AZD0530)
almost2years
m6A-related long noncoding RNAs predict prognosis and indicate therapeutic response in endometrial carcinoma. (PubMed, J Clin Lab Anal)
These findings contribute to understanding of the function of m6A-related lncRNAs in UCEC and provide promising therapeutic strategies for UCEC.
Journal
|
CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
|
Iclusig (ponatinib) • veliparib (ABT-888) • navitoclax (ABT 263) • saracatinib (AZD0530)
almost2years
Identification and validation of a novel cuproptosis-related lncRNA gene signature to predict prognosis and immune response in bladder cancer. (PubMed, Discov Oncol)
This study revealed the effects of CRLs on BCa and further established CRLs model, which can be used in clinic for predicting prognosis, immunological response and treatment sensitivity inpatient with BCa.
Journal • Gene Signature
|
TP53 (Tumor protein P53) • KMT2D (Lysine Methyltransferase 2D) • MUC16 (Mucin 16, Cell Surface Associated) • TTN (Titin)
|
TP53 mutation • MUC16 mutation
|
gemcitabine • paclitaxel • lapatinib • pazopanib • saracatinib (AZD0530)
2years
Opposite Effects of Src Family Kinases on YAP and ERK Activation in Pancreatic Cancer Cells: Implications for Targeted Therapy. (PubMed, Mol Cancer Ther)
Crucially, SFKs promoted YAP nuclear localization and phosphorylation at Tyr357, as shown by using the SFK inhibitors dasatinib, saracatinib, the preferential YES1 inhibitor CH6953755, siRNA-mediated knockdown of YES1, and transfection of epitogue-tagged YAP mutants in PANC-1 and Mia PaCa-2 cancer cells, models of the aggressive squamous subtype of PDAC. A combination of dasatinib and trametinib potently and synergistically inhibited colony formation by PDAC cells and suppessed the growth of MiaPaCa-2 cells xenografted into the flank of nude mice. The results provide rationale for considering a combination(s) of FDA-approved SFK (dasatinib) and MEK (e.g. trametinib) inhibitors in prospective clinical trials for the treatment of PDAC.
Journal
|
IGF1 (Insulin-like growth factor 1)
|
Mekinist (trametinib) • dasatinib • saracatinib (AZD0530)
over2years
Evaluating The Synergy Between Enzalutamide And Src Kinase Inhibitors In Castration-resistant Prostate Cancer (ENDO 2022)
By elucidating this synergy, we will provide critical pre-clinical data that could influence how future clinical trials are designed to increase the survival for men suffering from lethal CRPC. Learning Objective 1: Combination Therapy with kinase inhibitors may be a possible avenue to pursue in treating prostate cancer Learning Objective 2: Enzalutamide plus Saracatinib synergize together to yield greater prostate cancer cell death.
Late-breaking abstract
|
AR (Androgen receptor)
|
Xtandi (enzalutamide capsule) • saracatinib (AZD0530)
over2years
Protocol paper: a multi-center, double-blinded, randomized, 6-month, placebo-controlled study followed by 12-month open label extension to evaluate the safety and efficacy of Saracatinib in Fibrodysplasia Ossificans Progressiva (STOPFOP). (PubMed, BMC Musculoskelet Disord)
Clinical trials in rare diseases with limited study populations pose unique challenges. An ideal solution for limiting risks in early clinical studies is drug repositioning - using existing clinical molecules for new disease indications. Using existing assets may also allow a more fluid transition into clinical practice. With positive study outcome, AZD0530 may provide a therapy for FOP that can be rapidly progressed due to the availability of existing safety data from 28 registered clinical trials with AZD0530 involving over 600 patients.
Clinical protocol • Journal
|
ACVR1 (Activin A Receptor Type 1)
|
ACVR1 R206H
|
saracatinib (AZD0530)
over2years
SRC inhibitor saracatinib enhances efficacy of PD-1/PD-L1 immune checkpoint blockade in non-small cell lung cancer (AACR 2022)
Our in vivo and in vitro data demonstrated that SRC inhibitor saracatinib enhance T-cell-mediated anti-tumor immune responses in non-small lung cancer. We also provide evidence that support the combination of saracatinib and anti-PD-1/PD-L1 as a potential combination therapeutic approach to increase the efficacy of immunotherapy in non-small lung cancer.
Clinical • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • GZMB (Granzyme B)
|
PD-L1 expression • IFNG expression
|
saracatinib (AZD0530)
over2years
Inhibition of the CRM1 nuclear export protein can treat mutant KRAS tumors through stabilizing the DLC1 tumor suppressor protein (AACR 2022)
The three-drug combination of inhibitors of CRM1 (Selinexor), AKT (MK-2206), and SRC (Saracatinib), which is well-tolerated in mice, induced potent inhibition of tumor xenograft growth and was associated with induction of markers of apoptosis and senescence. Interestingly, KRAS siRNA knockdown phenocopied CRM1 inhibition, as it reduced cytoplasmic EZH2, DLC1 methylation, and DLC1 degradation. Our findings suggest CRM1 inhibitors, when given in conjunction with AKT and/or SRC kinase inhibitors, may have clinical efficacy against lung tumors with mutant KRAS.
IO biomarker
|
KRAS (KRAS proto-oncogene GTPase) • CUL4A (Cullin 4A) • XPO1 (Exportin 1)
|
KRAS mutation • EZH2 mutation • KRAS expression
|
Xpovio (selinexor) • MK-2206 • saracatinib (AZD0530)
3years
Assessing a Novel 3D Assay System for Drug Screening against OS Metastasis. (PubMed, Pharmaceuticals (Basel))
A post-hoc validation of the assay was possible by comparing the activity of a drug in our assay with early evidence of activity in human OS clinical trials (regorafenib and saracatinib). Despite the biological rationale, we found no evidence to support the use of oclacitinib as an antimetastatic agent in OS. The findings support our 3D BME assay as a highly efficient method to examine drugs for activity in targeting OS DTCs.
Journal
|
JAK1 (Janus Kinase 1)
|
Stivarga (regorafenib) • saracatinib (AZD0530)
over3years
[VIRTUAL] Pan-cancer analysis of SRC family kinases expression and sensitivity to SRC inhibitors. (EACR 2021)
Material and Methods We used four SFK inhibitors: dasatinib, bosutinib, saracatinib, and bafetinib, and measured sensitivity to these drugs for 30 cancer cell lines belonging to 12 different cancer types...Doxorubicin increased expression of all SFKs in HT-29 colon cancer cells and, in combination with dasatinib, also had a synergistic effect on cell growth...These findings have the potential to improve future strategies for the use of SFKs inhibitors in cancer treatment. This study was funded by RFBR, project number 20-34-70119.
Pan tumor
|
LYN (LYN Proto-Oncogene Src Family Tyrosine Kinase)
|
dasatinib • doxorubicin hydrochloride • Bosulif (bosutinib) • saracatinib (AZD0530) • bafetinib (INNO-406)
over3years
[VIRTUAL] Pan-cancer analysis of SRC family kinases expression and sensitivity to SRC inhibitors. (EACR 2021)
Material and Methods We used four SFK inhibitors: dasatinib, bosutinib, saracatinib, and bafetinib, and measured sensitivity to these drugs for 30 cancer cell lines belonging to 12 different cancer types...Doxorubicin increased expression of all SFKs in HT-29 colon cancer cells and, in combination with dasatinib, also had a synergistic effect on cell growth...These findings have the potential to improve future strategies for the use of SFKs inhibitors in cancer treatment. This study was funded by RFBR, project number 20-34-70119.
Pan tumor
|
LYN (LYN Proto-Oncogene Src Family Tyrosine Kinase)
|
dasatinib • doxorubicin hydrochloride • Bosulif (bosutinib) • saracatinib (AZD0530) • bafetinib (INNO-406)
over3years
[VIRTUAL] Pan-cancer analysis of SRC family kinases expression and sensitivity to SRC inhibitors. (EACR 2021)
Material and Methods We used four SFK inhibitors: dasatinib, bosutinib, saracatinib, and bafetinib, and measured sensitivity to these drugs for 30 cancer cell lines belonging to 12 different cancer types...Doxorubicin increased expression of all SFKs in HT-29 colon cancer cells and, in combination with dasatinib, also had a synergistic effect on cell growth...These findings have the potential to improve future strategies for the use of SFKs inhibitors in cancer treatment. This study was funded by RFBR, project number 20-34-70119.
Pan tumor
|
LYN (LYN Proto-Oncogene Src Family Tyrosine Kinase)
|
dasatinib • doxorubicin hydrochloride • Bosulif (bosutinib) • saracatinib (AZD0530) • bafetinib (INNO-406)
over3years
[VIRTUAL] Pan-cancer analysis of SRC family kinases expression and sensitivity to SRC inhibitors. (EACR 2021)
Material and Methods We used four SFK inhibitors: dasatinib, bosutinib, saracatinib, and bafetinib, and measured sensitivity to these drugs for 30 cancer cell lines belonging to 12 different cancer types...Doxorubicin increased expression of all SFKs in HT-29 colon cancer cells and, in combination with dasatinib, also had a synergistic effect on cell growth...These findings have the potential to improve future strategies for the use of SFKs inhibitors in cancer treatment. This study was funded by RFBR, project number 20-34-70119.
Pan tumor
|
LYN (LYN Proto-Oncogene Src Family Tyrosine Kinase)
|
dasatinib • doxorubicin hydrochloride • Bosulif (bosutinib) • saracatinib (AZD0530) • bafetinib (INNO-406)