Top 20 axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas tuyệt nhất 2022

Tác giả: khủng long molecular-cancer.biomedcentral.com

Ngày đăng khủng long : 6/5/2021

Xếp hạng khủng long : khủng long 3 ⭐ ( 5885 lượt đánh giá khủng long )

Xếp hạng khủng long cao nhất: 5 ⭐

Xếp hạng khủng long thấp nhất: 4 ⭐

Tóm tắt: khủng long Axl receptor tyrosine kinase is involved in the growth and metastasis and is an indicator of poor prognosis in several cancers including lung cancers. Although a mitogen-activated protein kinase (MAPK) pathway and an epithelial-to-mesenchymal transition (EMT) program are critical, molecular mechanisms underlying the Axl-driven cancer progression have not been fully elucidated. We aimed to identify molecules up-regulated by Axl kinase in lung adenocarcinomas. Through the global gene expression analysis and the functional annotation clustering, we found that AXL expression positively correlated with mRNA expressions of immune checkpoint molecules and chemokine receptors in non-small-cell lung cancers. Validation cohorts including our biobank confirmed that the AXL expression significantly correlated with expression of genes encoding programmed death-ligand1 (PD-L1) and CXC chemokine receptor 6 (CXCR6) in lung adenocarcinoma, especially in epidermal growth factor receptor (EGFR) mutation-positive adenocarcinoma. Pharmacological inhibition of Axl kinase activity decreased mRNA expressions of PD-L1 and CXCR6 in EGFR mutation-positive cell lines. Our data indicates the novel role of Axl kinase as a driver of immune checkpoint molecules and chemokine signalling pathways in the progression of lung adenocarcinomas. This study also highlights the necessity of clinical trials in order to test the efficacy of Axl kinase inhibition in the Axl-highly expressing subset of lung adenocarcinomas. 

Khớp với kết quả khủng long tìm kiếm: by Y Tsukita · 2019 · Cited by 33 Pharmacological inhibition of Axl kinase activity decreased mRNA expressions of PD-L1 and CXCR6 in EGFR mutation-positive cell lines. Our data ……

Tác giả: khủng long pubmed.ncbi.nlm.nih.gov

Ngày đăng khủng long : 18/1/2021

Xếp hạng khủng long : khủng long 3 ⭐ ( 95269 lượt đánh giá khủng long )

Xếp hạng khủng long cao nhất: 5 ⭐

Xếp hạng khủng long thấp nhất: 5 ⭐

Tóm tắt: khủng long Axl receptor tyrosine kinase is involved in the growth and metastasis and is an indicator of poor prognosis in several cancers including lung cancers. Although a mitogen-activated protein kinase (MAPK) pathway and an epithelial-to-mesenchymal transition (EMT) program are critical, molecular mechanis …

Khớp với kết quả khủng long tìm kiếm: by Y Tsukita · 2019 · Cited by 33 Our data indicates the novel role of Axl kinase as a driver of immune checkpoint molecules and chemokine signalling pathways in the progression ……

Tác giả: khủng long www.researchgate.net

Ngày đăng khủng long : 30/7/2021

Xếp hạng khủng long : khủng long 3 ⭐ ( 5057 lượt đánh giá khủng long )

Xếp hạng khủng long cao nhất: 5 ⭐

Xếp hạng khủng long thấp nhất: 5 ⭐

Tóm tắt: khủng long PDF | Axl receptor tyrosine kinase is involved in the growth and metastasis and is an indicator of poor prognosis in several cancers including lung… | Find, read and cite all the research you need on ResearchGate

Khớp với kết quả khủng long tìm kiếm: Pharmacological inhibition of Axl kinase activity decreased mRNA expressions of PD-L1 and CXCR6 in EGFR mutation-positive cell lines. Our data ……

Tác giả: khủng long tohoku.pure.elsevier.com

Ngày đăng khủng long : 23/6/2021

Xếp hạng khủng long : khủng long 1 ⭐ ( 68089 lượt đánh giá khủng long )

Xếp hạng khủng long cao nhất: 5 ⭐

Xếp hạng khủng long thấp nhất: 4 ⭐

Tóm tắt: khủng long Bài viết về Axl kinase drives immune checkpoint and chemokine … ( https://tohoku.pure.elsevier.com › publications › axl-ki… ) . Đang cập nhật…

Khớp với kết quả khủng long tìm kiếm: by Y Tsukita · 2019 · Cited by 33 Dive into the research topics of ‘Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas’. Together they ……

Tác giả: khủng long www.semanticscholar.org

Ngày đăng khủng long : 23/6/2021

Xếp hạng khủng long : khủng long 2 ⭐ ( 4044 lượt đánh giá khủng long )

Xếp hạng khủng long cao nhất: 5 ⭐

Xếp hạng khủng long thấp nhất: 5 ⭐

Tóm tắt: khủng long The data indicates the novel role of Axl kinase as a driver of immune checkpoint molecules and chemokine signalling pathways in the progression of lung adenocarcinomas. Axl receptor tyrosine kinase is involved in the growth and metastasis and is an indicator of poor prognosis in several cancers including lung cancers. Although a mitogen-activated protein kinase (MAPK) pathway and an epithelial-to-mesenchymal transition (EMT) program are critical, molecular mechanisms underlying the Axl-driven cancer progression have not been fully elucidated. We aimed to identify molecules up-regulated by Axl kinase in lung adenocarcinomas. Through the global gene expression analysis and the functional annotation clustering, we found that AXL expression positively correlated with mRNA expressions of immune checkpoint molecules and chemokine receptors in non-small-cell lung cancers. Validation cohorts including our biobank confirmed that the AXL expression significantly correlated with expression of genes encoding programmed death-ligand1 (PD-L1) and CXC chemokine receptor 6 (CXCR6) in lung adenocarcinoma, especially in epidermal growth factor receptor (EGFR) mutation-positive adenocarcinoma. Pharmacological inhibition of Axl kinase activity decreased mRNA expressions of PD-L1 and CXCR6 in EGFR mutation-positive cell lines. Our data indicates the novel role of Axl kinase as a driver of immune checkpoint molecules and chemokine signalling pathways in the progression of lung adenocarcinomas. This study also highlights the necessity of clinical trials in order to test the efficacy of Axl kinase inhibition in the Axl-highly expressing subset of lung adenocarcinomas. 

Khớp với kết quả khủng long tìm kiếm: The data indicates the novel role of Axl kinase as a driver of immune checkpoint molecules and chemokine signalling pathways in the progression of lung ……

Tác giả: khủng long www.springermedizin.de

Ngày đăng khủng long : 24/5/2021

Xếp hạng khủng long : khủng long 1 ⭐ ( 59155 lượt đánh giá khủng long )

Xếp hạng khủng long cao nhất: 5 ⭐

Xếp hạng khủng long thấp nhất: 2 ⭐

Tóm tắt: khủng long Axl receptor tyrosine kinase is involved in the growth and metastasis and is an indicator of poor prognosis in several cancers including lung cancers. Although a mitogen-activated protein kinase (MAPK) pathway and an epithelial-to-mesenchymal …

Khớp với kết quả khủng long tìm kiếm: Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas. Zeitschrift: Molecular Cancer > Ausgabe 1/ ……

Tác giả: khủng long www.mdpi.com

Ngày đăng khủng long : 17/4/2021

Xếp hạng khủng long : khủng long 2 ⭐ ( 120 lượt đánh giá khủng long )

Xếp hạng khủng long cao nhất: 5 ⭐

Xếp hạng khủng long thấp nhất: 2 ⭐

Tóm tắt: khủng long Bài viết về AXL Receptor in Cancer Metastasis and Drug Resistance … ( https://www.mdpi.com › pdf ) . Đang cập nhật…

Khớp với kết quả khủng long tìm kiếm: by A Auyez · 2021 · Cited by 2 Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas. Mol. Cancer 2019, 18, 24. [CrossRef]….

Tác giả: khủng long www.frontiersin.org

Ngày đăng khủng long : 21/5/2021

Xếp hạng khủng long : khủng long 3 ⭐ ( 43352 lượt đánh giá khủng long )

Xếp hạng khủng long cao nhất: 5 ⭐

Xếp hạng khủng long thấp nhất: 4 ⭐

Tóm tắt: khủng long A recently developed treatment strategy for lung cancer that combines immune checkpoint inhibitors with chemotherapy has been applied as a standard treatment for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), and it has improved the outcomes of chemotherapy. Maintenance treatment with anti-PD-1 antibody (aPD-1) enhances the effect of immunochemical combination therapy and improves therapeutic efficacy, which contributes toward a significant improvement in patient survival rates. The AXL receptor tyrosine kinase (AXL), which is expressed in tumor cells, plays an essential role in the resistance of cancers to chemotherapy and immunotherapy, and stimulates signaling associated with epithelial-mesenchymal transition (EMT) in metastatic cancer. AXL is thus an attractive target for controlling resistance to anti-tumor therapies. In this study, we examined the effect of AXL inhibitors on immune activation and tumor growth in TC1 and C3PQ mouse tumor models, in the context of clinical immunotherapy/chemotherapy and maintenance treatment, using an aPD-1 with/without pemetrexed. To determine the optimal timing for administration of SKI-G-801, an AXL inhibitor, we investigated its anti-tumor effects based on inclusion at the immunochemotherapy and maintenance therapy stages. We also performed flow cytometry-based immune profiling of myeloid cells and lymphoid cells at different points in the treatment schedule, to investigate the immune activation and anti-tumor …

Khớp với kết quả khủng long tìm kiếm: Axl Kinase Drives Immune Checkpoint and Chemokine Signalling Pathways in Lung Adenocarcinomas. Mol Cancer (2019) 18(1):24. doi: ……

Tác giả: khủng long jitc.bmj.com

Ngày đăng khủng long : 17/1/2021

Xếp hạng khủng long : khủng long 5 ⭐ ( 36591 lượt đánh giá khủng long )

Xếp hạng khủng long cao nhất: 5 ⭐

Xếp hạng khủng long thấp nhất: 4 ⭐

Tóm tắt: khủng long Background AXL receptor tyrosine kinase (AXL) is a transmembrane protein that is over-expressed in a variety of cancer and immune cells. AXL signaling has been implicated in creating an immunosuppressive tumor microenvironment (TME) through both tumor-intrinsic and immunomodulatory mechanisms1,2,3,4,5 promoting resistance to various therapies.6,7,8,9 Methods Compound inhibition potency against the kinase activity of AXL and other kinases was determined by detecting phosphorylated substrate using homogeneous time-resolved fluorescence (HTRF). Binding affinity of inhibitor to intracellular AXL kinase was determined by monitoring displacement of a competitive fluorescent tracer using an AXL NanoBRET assay. Recombinant Gas6, cancer cell lines, whole blood or isolated cells from healthy donors were used to determine the reduction in AXL-mediated signaling in-vitro. PK/PD and anti-tumor effects of selected AXL inhibitors were evaluated in murine models.Results AXL is highly expressed on a subset of immune cells, including DC’s, NK cells and M2 macrophages as well as fibroblasts, which contribute to a blunted anti-tumor response. Consistent with these observations, AXL is strongly associated with increased infiltration of macrophages, exhausted NK and T-cells, as well as significantly increased CD73 expression in multiple cancer types in TCGA. Additionally, AXL expression is strongly and significantly correlated with epithelial-mesenchymal transition (EMT), which further generates an immunosuppressive TME and promotes resistance to immune, targeted and chemotherapies. High expression of AXL is also strongly associated with poor survival in NSCLC, pancreatic, breast, head & neck, stomach, colorectal, ovarian & prostate adenocarcinomas, especially in the metastatic setting. AXL inhibitors that exhibit high potency in both biochemical (IC <5nM) and cell-based (IC <25nM) assays in addition to good selectivity against closely related kinases MER and TYRO3 (>90x and >25x fold selectivity, respectively) as well as other kinases involved in downstream signaling such as PI3K have been developed. Initial studies in animal models indicate a favorable pharmacokinetic profile and anti-tumor efficacy.Conclusions AXL is a promising therapeutic target involving both immunomodulatory and tumor-intrinsic mechanisms. AXL inhibition reduces the immunosuppressive TME, enables activation of an anti-tumor immune response and renders tumors more susceptible to previously resistant therapies. Highly potent and selective AXL inhibitors have been designed, displaying biological profiles superior to those of less-selective molecules currently advancing through clinical development.References 1. Gjerdrum C, Tiron C, Hoiby T, et al. Axl is an essential epithelial-to-mesenchymal transition-induced regulator of breast cancer metastasis and patient survival. PNAS 2010; 107(3):1124–1129.2. Ying X, Chen J, Huang X, Huang P, Yan S. Effect of AXL on the epithelial-to-mesenchymal transition in non-small cell lung cancer. Exp Ther Med 2017; 14 :785–790.3. Tsukita Y, Fujino N, Miyauchi E, et al. Axl Kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas. Molecular Cancer 2019; 18 :24.4. Terry S, Abdou A, Engelsen AST, et al. AXL targeting overcomes human lung cancer cell resistance to NK- and CTL-Mediated Cytotoxicity. Cancer Immunol Res 2019;7(11):1789–1802.5. Scutera S, Fraone T, Musso T, et al. Survival and migration of human dendritic cells are regulated by and IFN-alpha-Inducible Axl/Gas6 Pathway. J Immunol 2009; 183 :3004–3013.6. Wilson C, Ye X, Pham T, et al. AXL Inhibition sensitizes mesenchymal cancer cells to antimitotic drugs. Cancer Res 2014;74(20):5878–5890.7. Ludwig KF, Du W, Sorrelle NB, et al. Small-Molecule Inhibition of Axl targets tumor immune suppression and enhances chemotherapy in pancreatic cancer. Cancer Res 2018; 78(1):246–255.8. Brand TM, Iida M, Stein AP, et al. AXL mediates resistance to cetuximab therapy. Cancer Res 2015;74(18):5152–5164.9. Guo Z, Li Y, Zhang D, Ma J. Axl Inhibition induces the antitumor response which can be further potentiated by PD-1 blockade in the mouse cancer models. Oncotarget 2017; 8(52):89761–89774

Khớp với kết quả khủng long tìm kiếm: by S Paprcka · 2020 Axl Kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas. Molecular Cancer 2019;18:24. Terry S, Abdou A, Engelsen AST, ……

Tác giả: khủng long springernature.figshare.com

Ngày đăng khủng long : 26/6/2021

Xếp hạng khủng long : khủng long 5 ⭐ ( 44030 lượt đánh giá khủng long )

Xếp hạng khủng long cao nhất: 5 ⭐

Xếp hạng khủng long thấp nhất: 4 ⭐

Tóm tắt: khủng long Figure S1. A dose-dependent decrease in phosphorylation of Axl in PC9 cells by the Axl kinase inhibitor. Figure S2. Knockdown of Axl decreases mRNA expression of PD-L1, PD-L2 and CXCR6 in vitro. Figure S3. Immunoblots indicating decreases in phosphorylation of ERK1/2 and AKT by the Axl kinase inhibitor. Figure S4. A selective MEK1/2 inhibitor or an AKT inhibitor reduces PD-L1 mRNA expression in vitro. Figure S5. Diverse downstream pathways driven by Axl receptor tyrosine kinase in non-small-cell lung cancer. (DOCX 2506 kb)

Khớp với kết quả khủng long tìm kiếm: Additional file3: of Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas….

Tác giả: khủng long www.pnas.org

Ngày đăng khủng long : 6/3/2021

Xếp hạng khủng long : khủng long 5 ⭐ ( 21460 lượt đánh giá khủng long )

Xếp hạng khủng long cao nhất: 5 ⭐

Xếp hạng khủng long thấp nhất: 2 ⭐

Tóm tắt: khủng long Bài viết về Targeting Axl favors an antitumorigenic microenvironment that … ( https://www.pnas.org › content ) . Đang cập nhật…

Khớp với kết quả khủng long tìm kiếm: by MA Goyette · 2021 · Cited by 8 The receptor tyrosine kinase AXL is an HIF target, but its roles during … of Axl then enhanced an anti–PD-1 immune checkpoint blockade as ……

Tác giả: khủng long www.oncotarget.com

Ngày đăng khủng long : 18/2/2021

Xếp hạng khủng long : khủng long 1 ⭐ ( 74489 lượt đánh giá khủng long )

Xếp hạng khủng long cao nhất: 5 ⭐

Xếp hạng khủng long thấp nhất: 1 ⭐

Tóm tắt: khủng long https://doi.org/10.18632/oncotarget.27114 Takeshi Jimbo, Mana Hatanaka, Takahiro Komatsu, Tomoe Taira, Kentaro Kumazawa, Naoyuki Maeda, Takashi Suzuki, Masahiro Ota, Noriyasu Haginoya, Takeshi…

Khớp với kết quả khủng long tìm kiếm: by T Jimbo · 2019 · Cited by 13 The AXL receptor tyrosine kinase is involved in signal … M. Axl kinase drives immune checkpoint and chemokine signalling pathways in lung ……

Tác giả: khủng long www.dovepress.com

Ngày đăng khủng long : 14/7/2021

Xếp hạng khủng long : khủng long 4 ⭐ ( 34539 lượt đánh giá khủng long )

Xếp hạng khủng long cao nhất: 5 ⭐

Xếp hạng khủng long thấp nhất: 1 ⭐

Tóm tắt: khủng long Bài viết về Targeting AXL in NSCLC – Lung Cancer – Dove Medical Press ( https://www.dovepress.com › targeting-axl-in-nsclc-pee… ) . Đang cập nhật…

Khớp với kết quả khủng long tìm kiếm: by A Zaman · 2021 We also discuss current AXL kinase inhibitors and their clinical … activate cellular immune and inflammatory signaling pathways (such as ……

Tác giả: khủng long www.nature.com

Ngày đăng khủng long : 18/4/2021

Xếp hạng khủng long : khủng long 4 ⭐ ( 99658 lượt đánh giá khủng long )

Xếp hạng khủng long cao nhất: 5 ⭐

Xếp hạng khủng long thấp nhất: 3 ⭐

Tóm tắt: khủng long Bài viết về Axl and immune checkpoints inhibitors from fruiting bodies of … ( https://www.nature.com › articles ) . Đang cập nhật…

Khớp với kết quả khủng long tìm kiếm: Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas. Mol Cancer. 2019;18:1–6. Article Google Scholar….

Tác giả: khủng long www.hindawi.com

Ngày đăng khủng long : 18/2/2021

Xếp hạng khủng long : khủng long 1 ⭐ ( 623 lượt đánh giá khủng long )

Xếp hạng khủng long cao nhất: 5 ⭐

Xếp hạng khủng long thấp nhất: 1 ⭐

Tóm tắt: khủng long AXL is a receptor tyrosine kinase (RTK) that has been implicated in diverse tumor-promoting processes such as proliferation, migration, invasion, survival, and apoptosis. AXL therefore plays a role in cancer progression, and AXL has been implicated in a wide variety of malignancies from solid tumors to hematopoietic cancers where it is often associated with poor prognosis. In cancer, AXL has been shown to promote epithelial to mesenchymal transition (EMT), metastasis formation, drug resistance, and a role for AXL in modulation of the tumor microenvironment and immune response has been identified. In light of these activities multiple AXL inhibitors have been developed, and several of these have entered clinical trials in the U.S. In breast cancer, high levels of AXL expression have been observed. The role of AXL in cancer with a focus on therapeutic implications for breast cancer is discussed.

Khớp với kết quả khủng long tìm kiếm: by SA Colavito · Cited by 20 Changes in Cell Signaling Pathways as a Goal of Targeted Therapy of Solid … “Axl kinase drives immune checkpoint and chemokine signalling pathways in lung ……

Tác giả: khủng long www.cancerindex.org

Ngày đăng khủng long : 3/6/2021

Xếp hạng khủng long : khủng long 2 ⭐ ( 50549 lượt đánh giá khủng long )

Xếp hạng khủng long cao nhất: 5 ⭐

Xếp hạng khủng long thấp nhất: 2 ⭐

Tóm tắt: khủng long Bài viết về AXL | Cancer Genetics Web – CancerIndex ( http://www.cancerindex.org › geneweb › AXL ) . Đang cập nhật…

Khớp với kết quả khủng long tìm kiếm: Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas. Mol Cancer. 2019; 18(1):24 [PubMed] Free ……

Tác giả: khủng long www.bergenbio.com

Ngày đăng khủng long : 11/5/2021

Xếp hạng khủng long : khủng long 5 ⭐ ( 94227 lượt đánh giá khủng long )

Xếp hạng khủng long cao nhất: 5 ⭐

Xếp hạng khủng long thấp nhất: 5 ⭐

Tóm tắt: khủng long Bài viết về Axl inhibitors for aggressive disease – BerGenBio ( https://www.bergenbio.com › uploads › 2020/01 ) . Đang cập nhật…

Khớp với kết quả khủng long tìm kiếm: Tsukita et al., (2019) Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas. Mol Cancer….

Tác giả: khủng long www.sciencegate.app

Ngày đăng khủng long : 24/7/2021

Xếp hạng khủng long : khủng long 2 ⭐ ( 96945 lượt đánh giá khủng long )

Xếp hạng khủng long cao nhất: 5 ⭐

Xếp hạng khủng long thấp nhất: 2 ⭐

Tóm tắt: khủng long Bài viết về Axl Receptor Tyrosine Kinase Latest Research Papers | ScienceGate ( https://www.sciencegate.app › keywords ) . Đang cập nhật…

Khớp với kết quả khủng long tìm kiếm: Axl Kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas. Molecular Cancer 2019;18:24.Terry S, Abdou A, Engelsen AST, ……

Tác giả: khủng long www.storkapp.me

Ngày đăng khủng long : 4/3/2021

Xếp hạng khủng long : khủng long 2 ⭐ ( 10174 lượt đánh giá khủng long )

Xếp hạng khủng long cao nhất: 5 ⭐

Xếp hạng khủng long thấp nhất: 4 ⭐

Tóm tắt: khủng long Bài viết về Predicting the Specificity- Determining Positions of Receptor … – Stork ( https://www.storkapp.me › pubpaper ) . Đang cập nhật…

Khớp với kết quả khủng long tìm kiếm: … Positions of Receptor Tyrosine Kinase Axl Front Mol Biosci 8() 658906 … Axl kinase drives immune checkpoint and chemokine signalling pathways in lung ……

Tác giả: khủng long jcmtjournal.com

Ngày đăng khủng long : 28/1/2021

Xếp hạng khủng long : khủng long 5 ⭐ ( 40566 lượt đánh giá khủng long )

Xếp hạng khủng long cao nhất: 5 ⭐

Xếp hạng khủng long thấp nhất: 2 ⭐

Tóm tắt: khủng long The role of immune checkpoint inhibitors in triple-negative breast cancer: recent developments and future perspectives

Khớp với kết quả khủng long tìm kiếm: by M Papadimitriou · 2021 Blocking AXL signaling with BGB324 has been shown to enhance the effect of immune checkpoint blockade in lung and mammary adenocarcinoma ……