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Precision medicine in acute lymphoblastic leukemia

Ching-Hon Pui

Frontiers of Medicine 2020, Volume 14, Issue 6,   Pages 689-700 doi: 10.1007/s11684-020-0759-8

Abstract: The cure rate of childhood acute lymphoblastic leukemia (ALL) has exceeded 90% in some contemporary clinical trials. However, the dose intensity of conventional chemotherapy has been pushed to its limit. Further improvement in outcome will need to rely more heavily on molecular therapeutic as well as immuno- and cellular-therapy approaches together with precise risk stratification. Children with or hyperdiploid>50 ALL who achieve negative minimal residual disease during early remission induction are suitable candidates for reduction in treatment. Patients with Philadelphia chromosome (Ph)-positive or Ph-like ALL with ABL-class fusion should be treated with dasatinib. BH3 profiling and other preclinical methods have identified several high-risk subtypes, such as hypodiplod, early T-cell precursor, immature T-cell, -rearranged, Ph-positive and -positive ALL, that may respond to BCL-2 inhibitor venetoclax. There are other fusions or mutations that may serve as putative targets, but effective targeted therapy has yet to be established. For other high-risk patients or poor early treatment responders who do not have targetable genetic lesions, current approaches that offer hope include blinatumomab, inotuzumab and CAR-T cell therapy for B-ALL, and daratumumab and nelarabine for T-ALL. With the expanding therapeutic armamentarium, we should start focus on rational combinations of targeted therapy with non-overlapping toxicities.

Keywords： acute lymphoblastic leukemia     molecular therapeutics     targeted therapy     tyrosine kinase inhibitors     immunotherapy    

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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 theThe mechanisms of resistance to third-generation inhibitors reported to date include the EGFR

Keywords： EGFR     tyrosine kinase inhibitor     AZD9291     EAI045    

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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 inhibitorsconsider the problems of signaling pathway redundancy and how the activation of different receptor tyrosine

Keywords： targeted therapy     drug resistance     receptor tyrosine kinases     cancer    

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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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Mitogen-activated protein kinase pathway inhibitors: inhibitors for diseases?

Xu WANG MS, Xiao-Wei GONG MD, PhD, Yong JIANG MD, PhD, Yu-Hua LI PhD,

Frontiers of Medicine 2010, Volume 4, Issue 1,   Pages 46-53 doi: 10.1007/s11684-010-0010-0

Abstract: Mitogen-activated protein kinase (MAPK) signaling pathway, one of the most important signaling pathwaysSo far, inhibitors specifically against each subfamilies of MAP kinase have been developed, while moreMost of the kinase inhibitors exert their functions in an ATP-competitive way or a non-ATP-competitiveFurther studies on the effective mechanism of the MAPK inhibitors and their therapeutic roles in theinhibitors, and the therapy of diseases caused by the dysfunction of the MAPK pathway.

Keywords： mitogen-activated protein kinase     drug target     inhibitor     signal transduction     disease    

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Targeted therapy of desmoid-type fibromatosis: mechanism, current situation, and future prospects

Zhen Wang, Jianhui Wu, Xiuyun Tian, Chunyi Hao

Frontiers of Medicine 2019, Volume 13, Issue 4,   Pages 427-437 doi: 10.1007/s11684-018-0672-6

Abstract: Tyrosine kinase and γ-secretase inhibitors are primarily used in the targeted therapy of DF.

Keywords： targeted therapy     desmoid-type fibromatosis     tyrosine kinase inhibitor     γ-secretase inhibitor    

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Medical oncology management of advanced hepatocellular carcinoma 2019: a reality check

Amy Lee, Fa-Chyi Lee

Frontiers of Medicine 2020, Volume 14, Issue 3,   Pages 273-283 doi: 10.1007/s11684-019-0728-2

Abstract: Up until 2017, treatment of advanced HCC was largely limited to sorafenib, an oral tyrosine kinase inhibitorAs of 2019, the US FDA has approved four oral tyrosine kinase inhibitors, two immune checkpoint inhibitorsThe expected breakthrough of using immune checkpoint inhibitors in advanced HCC did not materialize inThe use of immune checkpoint inhibitors in conjunction with oral tyrosine kinase inhibitors or anti-angiogenesis

Keywords： hepatocellular carcinoma     tyrosine kinase inhibitor     check point inhibitor     anti-angiogenesis    

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Atomistic characterization of binding modes and affinity of peptide inhibitors to amyloid-

Fufeng LIU,Wenjie DU,Yan SUN,Jie ZHENG,Xiaoyan DONG

Frontiers of Chemical Science and Engineering 2014, Volume 8, Issue 4,   Pages 433-444 doi: 10.1007/s11705-014-1454-6

Abstract: Previous studies have found that three peptide inhibitors (i.e., KLVFF, VVIA, and LPFFD) can inhibitHowever, atomic details of binding modes and binding affinities between these peptide inhibitors andAll inhibitors exhibit varied binding affinity to A , in which KLVFF has the highest binding affinityMM/PBSA analysis further revealed that different peptide inhibitors have different modes of interactionSpecific residue-based interactions between inhibitors and A were determined and compared for illustrating

Keywords： Alzheimer’s disease     amyloid β-protein     peptide inhibitors     protein-protein interaction     molecular    

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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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Synthesis of mono and bis-4-methylpiperidiniummethyl-urea as corrosion inhibitors for steel in acidic

Abbas TEIMOURI, Nasrin SOLTANI, Alireza Najafi CHERMAHINI

Frontiers of Chemical Science and Engineering 2011, Volume 5, Issue 1,   Pages 43-50 doi: 10.1007/s11705-010-0532-7

Abstract: Mono and bis-4-methylpiperidiniummethyl urea were synthesized, characterized and used as new corrosion inhibitorsPotentiodynamic polarization measurements showed that two inhibitors are mixed type.This reveals that inhibitive actions of inhibitors were mainly due to adsorption on mild steel surface

Keywords： corrosion inhibitors     mild steel     acidic medium     theoretical studies     DFT    

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Screening responsive or resistant biomarkers of immune checkpoint inhibitors based on online databases

Zhen Xiang, Yingyan Yu

Frontiers of Medicine 2019, Volume 13, Issue 1,   Pages 24-31 doi: 10.1007/s11684-019-0679-7

Abstract: Immune checkpoint inhibitors are a promising strategy in the treatment of cancer, especially advancedHowever, not all patients are responsive to immune checkpoint inhibitors.of data, which allow researchers to explore responsive or resistant biomarkers of immune checkpoint inhibitors

Keywords： immune checkpoint blockade     sensitivity     resistance     data mining    

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Analysis of interactions of immune checkpoint inhibitors with antibiotics in cancer therapy

Frontiers of Medicine 2022, Volume 16, Issue 3,   Pages 307-321 doi: 10.1007/s11684-022-0927-0

Abstract: The discovery of immune checkpoint inhibitors, such as PD-1/PD-L1 and CTLA-4, has played an importantwidely applied in clinical treatment, and they are inevitably used in combination with immune checkpoint inhibitorsClinical practice has revealed that antibiotics can weaken the therapeutic response to immune checkpoint inhibitorsStudies have shown that the gut microbiota is essential for the interaction between immune checkpoint inhibitorsThis review focuses on the interactions between immune checkpoint inhibitors and antibiotics, with an

Keywords： tumor immunotherapy     immune checkpoint inhibitor     antibiotics     gut microbiota     drug–drug interaction    

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Four-year follow-up of patients with imatinib-resistant or intolerant chronic myeloid leukemia receiving dasatinib: efficacy and safety

Xiaojun Huang, Qian Jiang, Jianda Hu, Jianyong Li, Jie Jin, Fanyi Meng, Zhixiang Shen, Ting Liu, Depei Wu, Jianmin Wang, Jianxiang Wang

Frontiers of Medicine 2019, Volume 13, Issue 3,   Pages 344-353 doi: 10.1007/s11684-018-0639-7

Abstract: Dasatinib is a highly effective second-generation tyrosine kinase inhibitor used to treat chronic myeloid

Keywords： chronic myeloid leukemia (CML)     dasatinib     tyrosine kinase inhibitor     long-term follow-up    

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The role of protein kinase C epsilon in neural signal transduction and neurogenic diseases

Yuan CHEN, Qi TIAN

Frontiers of Medicine 2011, Volume 5, Issue 1,   Pages 70-76 doi: 10.1007/s11684-011-0119-9

Abstract:

Protein kinase C epsilon (PKC ?) is one of major isoforms in novel PKC family.

Keywords： protein kinase C ?     signal transduction     neurogenic disease    

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Advances in newly developing therapy for chronic hepatitis C virus infection

Paul J. Pockros

Frontiers of Medicine 2014, Volume 8, Issue 2,   Pages 166-174 doi: 10.1007/s11684-014-0334-2

Abstract:

Chronic hepatitis C virus (HCV) infection afflicts a reported 170 million people worldwide and is often complicated by cirrhosis and hepatocellular carcinoma. Morbidity and mortality are decreased with the successful treatment of chronic HCV infection. Increased understanding of the HCV has allowed further development of new direct-acting antiviral (DAA) agents against the HCV and has also allowed the development of IFN-free oral treatment regimens. In late 2013 the first nucleotide polymerase inhibitor regimen with RBV alone for genotypes 2/3 and in combination with a 12-week regimen of PEG-IFN+RBV for genotypes 1, 4 was approved for use in the US. A number of promising new DAA regimens which are IFN-free are in phase 3 development and the first will likely be approved for use in the US in 2014. The currently approved regimens are discussed in detail and currently available data on future regimens are reviewed herein.

Keywords： direct-acting antiviral (DAA)     nucleotide polymerase inhibitors     protease inhibitors    

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Title Author Date Type Operation

Precision medicine in acute lymphoblastic leukemia

Ching-Hon Pui

Journal Article

Mechanisms of resistance to third-generation EGFR tyrosine kinase inhibitors

Shuhang Wang,Yongping Song,Feifei Yan,Delong Liu

Journal Article

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

Peter B. Alexander,Xiao-Fan Wang

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

Mitogen-activated protein kinase pathway inhibitors: inhibitors for diseases?

Xu WANG MS, Xiao-Wei GONG MD, PhD, Yong JIANG MD, PhD, Yu-Hua LI PhD,

Journal Article

Targeted therapy of desmoid-type fibromatosis: mechanism, current situation, and future prospects

Zhen Wang, Jianhui Wu, Xiuyun Tian, Chunyi Hao

Journal Article

Medical oncology management of advanced hepatocellular carcinoma 2019: a reality check

Amy Lee, Fa-Chyi Lee

Journal Article

Atomistic characterization of binding modes and affinity of peptide inhibitors to amyloid-

Fufeng LIU,Wenjie DU,Yan SUN,Jie ZHENG,Xiaoyan DONG

Journal Article

Dual faces of SH2-containing protein-tyrosine phosphatase

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

Journal Article

Synthesis of mono and bis-4-methylpiperidiniummethyl-urea as corrosion inhibitors for steel in acidic

Abbas TEIMOURI, Nasrin SOLTANI, Alireza Najafi CHERMAHINI

Journal Article

Screening responsive or resistant biomarkers of immune checkpoint inhibitors based on online databases

Zhen Xiang, Yingyan Yu

Journal Article

Analysis of interactions of immune checkpoint inhibitors with antibiotics in cancer therapy

Journal Article

Four-year follow-up of patients with imatinib-resistant or intolerant chronic myeloid leukemia receiving dasatinib: efficacy and safety

Xiaojun Huang, Qian Jiang, Jianda Hu, Jianyong Li, Jie Jin, Fanyi Meng, Zhixiang Shen, Ting Liu, Depei Wu, Jianmin Wang, Jianxiang Wang

Journal Article

The role of protein kinase C epsilon in neural signal transduction and neurogenic diseases

Yuan CHEN, Qi TIAN

Journal Article

Advances in newly developing therapy for chronic hepatitis C virus infection

Paul J. Pockros

Journal Article