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Resistance to receptor tyrosine kinase inhibition in cancer: molecular mechanisms and therapeutic strategies

Peter B. Alexander,Xiao-Fan Wang

Frontiers of Medicine 2015, Volume 9, Issue 2,   Pages 134-138 doi: 10.1007/s11684-015-0396-9

Abstract: In this review, we discuss the main known mechanisms of resistance to receptor tyrosine kinase inhibitorsoutput, and consider the problems of signaling pathway redundancy and how the activation of different receptortyrosine kinases translates into intracellular signal transduction in different cancer types.

Keywords： targeted therapy     drug resistance     receptor tyrosine kinases     cancer    

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Mechanisms of resistance to third-generation EGFR tyrosine kinase inhibitors

Shuhang Wang,Yongping Song,Feifei Yan,Delong Liu

Frontiers of Medicine 2016, Volume 10, Issue 4,   Pages 383-388 doi: 10.1007/s11684-016-0488-1

Abstract:

The tyrosine kinase inhibitors (TKI) of the epidermal growth factor receptor (EGFR) are becoming the

Keywords： EGFR     tyrosine kinase inhibitor     AZD9291     EAI045    

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Dual faces of SH2-containing protein-tyrosine phosphatase

Shuangwei Li, Diane DiFang Hsu, Hongyang Wang, Gen-Sheng Feng

Frontiers of Medicine 2012, Volume 6, Issue 3,   Pages 275-279 doi: 10.1007/s11684-012-0216-4

Abstract:

PTPN11, which encodes tyrosine phosphatase Shp2, is a critical gene mediating cellular responses toAgainst original prediction as tumor suppressor for tyrosine phosphatases, PTPN11 was first

Keywords： PTPN11/Shp2     leukemia     hepatocellular carcinoma     mutation    

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Effect of inhibiting tyrosine kinase Src expression on protein phosphatase 2A and tau phosphorylation

LIU Rong, ZENG Ji, ZHOU Xinwen, WANG Jianzhi, PEI Jinjing

Frontiers of Medicine 2008, Volume 2, Issue 3,   Pages 235-238 doi: 10.1007/s11684-008-0044-8

Abstract: The aim of this study is to investigate the effect of tyrosine kinase Src on Tyrosine 307(Y307) phosphorylation

Keywords： hyperphosphorylation     PP2A activity     cellular regulation     siRNA     siRNA transfection    

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Nicotinic acetylcholine receptor α7 subunit: a novel therapeutic target for cardiovascular diseases

Chong Liu, Dingfeng Su

Frontiers of Medicine 2012, Volume 6, Issue 1,   Pages 35-40 doi: 10.1007/s11684-012-0171-0

Abstract: cholinergic anti-inflammatory pathway,” more specifically via the α7 nicotinic acetylcholine receptor

Keywords： α7 nicotinic acetylcholine receptor     cardiovascular diseases     baroreflex sensitivity    

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Overcoming resistance to endocrine therapy in hormone receptor-positive human epidermal growth factorreceptor 2-negative (HR

Wenjie Zhu, Binghe Xu

Frontiers of Medicine 2021, Volume 15, Issue 2,   Pages 208-220 doi: 10.1007/s11684-020-0795-4

Abstract: New targeted therapies have been developed to overcome resistance to endocrine therapy (ET) and improve the outcome of HR /HER2 advanced breast cancer (ABC). We conducted a meta-analysis and systemic review on randomized controlled trials evaluating various targeted therapies in combination with ET in HR /HER2 ABC. PUBMED and EMBASE databases were searched for eligible trials. Hazard ratios (HRs) for progression-free survival (PFS), odds ratios (ORs) for objective response rate (ORR), clinical benefit rate (CBR), and toxicity were meta-analyzed. Twenty-six studies with data on 10 347 patients were included and pooled. The addition of cyclin-dependent kinase 4/6 inhibitors to ET significantly improved median PFS (pooled HR= 0.547, <0.001), overall survival (pooled HR= 0.755, <0.001), and tumor response rates (ORR, pooled OR= 1.478, <0.001; CBR, pooled OR= 1.201, <0.001) with manageable toxicities (pooled OR= 3.280, <0.001). The mammalian targets of rapamycin inhibitors and exemestane were not clinically beneficial for this pooled population including ET-naïve and ET-resistant patients. Moderate improvement in PFS (pooled HR= 0.686, <0.001) yet pronounced toxicities (pooled OR= 2.154, <0.001) were noted in the combination of phosphatidylinositol-4,5-bisphosphate 3-kinase inhibitors with fulvestrant. Future studies are warranted to optimize the population and the dosing sequence of these available options.

Keywords： endocrine-resistant     HR+/HER2- advanced breast cancer     randomized clinical trials     meta-analysis     targeted therapy    

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microenvironment contributes to tumor progression in diffuse large B-cell lymphoma upon anti-CD19 chimeric antigen receptor

Frontiers of Medicine 2023, Volume 17, Issue 4,   Pages 699-713 doi: 10.1007/s11684-022-0972-8

Abstract: Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%–50

Keywords： anti-CD19 chimeric antigen receptor T     immunotherapy     diffuse large B cell lymphoma     tumor microenvironment    

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Chimeric antigen receptor T cell therapies for acute myeloid leukemia

Bin Gu, Jianhong Chu, Depei Wu

Frontiers of Medicine 2020, Volume 14, Issue 6,   Pages 701-710 doi: 10.1007/s11684-020-0763-z

Abstract: Abstract Chimeric antigen receptor T cell (CAR T) therapies have achieved unprecedented efficacy in B-cell

Keywords： acute myeloid leukemia     CAR T     immunotherapy    

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Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy

Zhao Zhang, Jun Jiang, Xiaodong Wu, Mengyao Zhang, Dan Luo, Renyu Zhang, Shiyou Li, Youwen He, Huijie Bian, Zhinan Chen

Frontiers of Medicine 2019, Volume 13, Issue 1,   Pages 57-68 doi: 10.1007/s11684-019-0683-y

Abstract: In recent years, the development of tumor immunotherapy especially chimeric antigen receptor T (CAR-TEpidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation expressed in various

Keywords： chimeric antigen receptor T cells     epidermal growth factor receptor     lung cancer     immunotherapy     tumor immunolog    

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Blockage of receptor-interacting protein 2 expression by small interfering RNA in murine macrophages

LIU Hongchun, CAO Zhongwei, JIN Jianjun, WANG Jiyao

Frontiers of Medicine 2008, Volume 2, Issue 2,   Pages 166-170 doi: 10.1007/s11684-008-0030-1

Abstract: This study aims to demonstrate that blocking the receptor-interacting protein2 (Rip2) expression can
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Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1): a potential biomarker for the diagnosis

Changlin Cao, Jingxian Gu, Jingyao Zhang

Frontiers of Medicine 2017, Volume 11, Issue 2,   Pages 169-177 doi: 10.1007/s11684-017-0505-z

Abstract: An example of these biomarkers is triggering receptor expressed on myeloid cell-1 (TREM-1), which isa cell surface receptor expressed on monocytes/macrophages and neutrophils.

Keywords： soluble triggering receptor expressed on myeloid cells-1     infectious diseases     diagnosis and prognosis    

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Gene and protein expression of proteinase-activated receptor-1, 2 in a murine model of acute graft host

Quan LI MD , Weiming LI MD , Ping ZOU MD , Jian ZHANG BM ,

Frontiers of Medicine 2009, Volume 3, Issue 3,   Pages 309-315 doi: 10.1007/s11684-009-0043-4

Abstract: Proteinase-activated receptors (PARs) are a novel subclass of seven transmembrane-spanning, G protein-coupled receptors. PAR-1 and PAR-2 are widely expressed in a variety of cells and are found to be involved in many physiological and pathological processes including inflammation and immune response. However, little is known about the function of PAR-1, 2 in acute graft host disease (GVHD). In the present study, we first detected the expression of PAR-1, 2 protein and mRNA in a murine model of acute GVHD using the methods of immunohistochemistry, Western blot and quantitative real-time polymerase chain reaction (PCR). Syngeneic hematopoietic stem cell transplantation (HSCT) mice served as controls. The relative gene expression level of PAR-1 was significantly increased in the skin, liver, small intestine of allogeneic HSCT mice (in skin: 0.039±0.013 0.008±0.002 of controls, =0.009; in liver: 0.165±0.006 0.017±0.006 of controls, =0.004; in small intestine: 0.215±0.009 0.016±0.002 of controls, =0.003), but not in the stomach, lung and kidney of allogeneic HSCT mice (>0.05). PAR-2 mRNA expression in the liver and small intestine of allogeneic HSCT mice (in liver: 0.010±0.002 0.003±0.001 of controls, =0.008; in small intestine: 0.006±0.001 0.003±0.001 of controls, =0.024) was increased significantly, but PAR-2 mRNA expression in the other organs (>0.05) was not found to be significantly elevated. PAR-1, 2 protein expression was in accordance with the mRNA expression, as shown by Western blot. Using immunohistochemistry the present study demonstrated that there was strong PAR-1, 2 immunoreactivity in the epithelial cell and vascular endothelial cell of target organs of acute GVHD. Our findings of markedly increased expression of PAR-1, 2 in target organs of acute GVHD suggest that PAR-1 and PAR-2 may play an important role in the pathogenesis of acute GVHD.

Keywords： graft vs host disease     proteinase-activated receptor     murine model     hematopoietic stem cell transplantation    

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A giant step forward: chimeric antigen receptor T-cell therapy for lymphoma

Houli Zhao, Yiyun Wang, Elaine Tan Su Yin, Kui Zhao, Yongxian Hu, He Huang

Frontiers of Medicine 2020, Volume 14, Issue 6,   Pages 711-725 doi: 10.1007/s11684-020-0808-3

Abstract: Chimeric antigen receptor T (CAR-T) cells were introduced as a treatment for these patients.

Keywords： chimeric antigen receptor T (CAR-T) cell     lymphoma     cytokine release syndrome (CRS)     immune effector cell-associated    

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Effects of intracerebroventricular NMDA and non-NMDA receptor agonists or antagonists on general anesthesia

XU Aijun, TIAN Yuke, DUAN Shiming

Frontiers of Medicine 2007, Volume 1, Issue 2,   Pages 207-210 doi: 10.1007/s11684-007-0039-x

Abstract: The effects of intracerebroventricular (icv) agonists and antagonists of -methyl--aspartate (NMDA) and alpha-amino-3-hydroxy 5-methyl-4-isoxazole-propionic acid (AMPA) receptors on the general anesthesia of propofol were studied. A total of 144 Kunming mice, male and female with body mass of (22?3) g, were used. Part One of the Experiment: a total of 104 Kunming mice, male and female, were randomly divided into 13 groups. Intracerebroventricular artificial cerebral fluid (aCSF) or different doses of NMDA, AMPA, MK-801 or NBQX was injected immediately after intravenously administered propofol 25 mg/kg and the recovery time following the loss of righting reflex (LORR) was recorded. Part Two of the Experiment: a total of 40 Kunming female mice were divided randomly into 5 groups and injected with icv aCSF or NMDA, AMPA, MK-801 or NBQX after intraperitoneally administered propofol 50 mg/kg. The pain threshold of the mice was then investigated by hot-plate test (HPPT). NMDA (0.05 or 0.075?g, icv) or AMPA (0.05 ?g, icv) exhibited no effects on the LORR, but NMDA (0.1 μg, icv) or AMPA (0.075 or 0.1 ?g, icv) prolonged the LORR significantly compared with the aCSF group (<0.05, <0.01). The LORR of the 2 μg MK-801 group had no changes, while those of the 4 or 8 μg MK-801 groups were prolonged significantly. The LORR of the 0.5, 2 or 4 μg NBQX groups were all prolonged significantly. NMDA 0.05 ?g or AMPA 0.05 ?g decreased the pain threshold slightly but did not differ in effect compared with the aCSF group; 2 μg MK-801 or 0.5 μg NBQX both increased the pain threshold significantly. Our results indicate that propofol produces general anesthesia partly through an interaction with brain NMDA and AMPA receptors in mice.
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affect the survival of patients with relapsed or refractory non-Hodgkin lymphoma after chimeric antigen receptor

Lili Zhou, Ping Li, Shiguang Ye, Xiaochen Tang, Junbang Wang, Jie Liu, Aibin Liang

Frontiers of Medicine 2020, Volume 14, Issue 6,   Pages 786-791 doi: 10.1007/s11684-020-0751-3

Abstract: Factors associated with complete and durable remissions after anti-CD19 chimeric antigen receptor T (

Keywords： anti-CD19 chimeric antigen receptor T cell     soft tissue     bone marrow     relapsed or refractory non-Hodgkin    

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Title Author Date Type Operation

Resistance to receptor tyrosine kinase inhibition in cancer: molecular mechanisms and therapeutic strategies

Peter B. Alexander,Xiao-Fan Wang

Journal Article

Mechanisms of resistance to third-generation EGFR tyrosine kinase inhibitors

Shuhang Wang,Yongping Song,Feifei Yan,Delong Liu

Journal Article

Dual faces of SH2-containing protein-tyrosine phosphatase

Shuangwei Li, Diane DiFang Hsu, Hongyang Wang, Gen-Sheng Feng

Journal Article

Effect of inhibiting tyrosine kinase Src expression on protein phosphatase 2A and tau phosphorylation

LIU Rong, ZENG Ji, ZHOU Xinwen, WANG Jianzhi, PEI Jinjing

Journal Article

Nicotinic acetylcholine receptor α7 subunit: a novel therapeutic target for cardiovascular diseases

Chong Liu, Dingfeng Su

Journal Article

Overcoming resistance to endocrine therapy in hormone receptor-positive human epidermal growth factorreceptor 2-negative (HR

Wenjie Zhu, Binghe Xu

Journal Article

microenvironment contributes to tumor progression in diffuse large B-cell lymphoma upon anti-CD19 chimeric antigen receptor

Journal Article

Chimeric antigen receptor T cell therapies for acute myeloid leukemia

Bin Gu, Jianhong Chu, Depei Wu

Journal Article

Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy

Zhao Zhang, Jun Jiang, Xiaodong Wu, Mengyao Zhang, Dan Luo, Renyu Zhang, Shiyou Li, Youwen He, Huijie Bian, Zhinan Chen

Journal Article

Blockage of receptor-interacting protein 2 expression by small interfering RNA in murine macrophages

LIU Hongchun, CAO Zhongwei, JIN Jianjun, WANG Jiyao

Journal Article

Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1): a potential biomarker for the diagnosis

Changlin Cao, Jingxian Gu, Jingyao Zhang

Journal Article

Gene and protein expression of proteinase-activated receptor-1, 2 in a murine model of acute graft host

Quan LI MD , Weiming LI MD , Ping ZOU MD , Jian ZHANG BM ,

Journal Article

A giant step forward: chimeric antigen receptor T-cell therapy for lymphoma

Houli Zhao, Yiyun Wang, Elaine Tan Su Yin, Kui Zhao, Yongxian Hu, He Huang

Journal Article

Effects of intracerebroventricular NMDA and non-NMDA receptor agonists or antagonists on general anesthesia

XU Aijun, TIAN Yuke, DUAN Shiming

Journal Article

affect the survival of patients with relapsed or refractory non-Hodgkin lymphoma after chimeric antigen receptor

Lili Zhou, Ping Li, Shiguang Ye, Xiaochen Tang, Junbang Wang, Jie Liu, Aibin Liang

Journal Article