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Progress and challenges in RET-targeted cancer therapy

Frontiers of Medicine 2023, Volume 17, Issue 2,   Pages 207-219 doi: 10.1007/s11684-023-0985-y

Abstract: The rearranged during transfection (RET) is a receptor protein tyrosine kinase. Oncogenic RET fusions or mutations are found most often in non-small cell lung cancer (NSCLC) and in thyroid cancer, but also increasingly in various types of cancers at low rates. In the last few years, two potent and selective RET protein tyrosine kinase inhibitors (TKIs), pralsetinib (BLU-667) and selpercatinib (LOXO-292, LY3527723) were developed and received regulatory approval. Although pralsetinib and selpercatinib gave high overall response rates (ORRs), < 10% of patients achieved a complete response (CR). The RET TKI-tolerated residual tumors inevitably develop resistance by secondary target mutations, acquired alternative oncogenes, or MET amplification. RET G810 mutations located at the kinase solvent front site were identified as the major on-target mechanism of acquired resistance to both selpercatinib and pralsetinib. Several next-generation of RET TKIs capable of inhibiting the selpercatinib/pralsetinib-resistant RET mutants have progressed to clinical trials. However, it is likely that new TKI-adapted RET mutations will emerge to cause resistance to these next-generation of RET TKIs. Solving the problem requires a better understanding of the multiple mechanisms that support the RET TKI-tolerated persisters to identify a converging point of vulnerability to devise an effective co-treatment to eliminate the residual tumors.

Keywords： pralsetinib     selpercatinib     RET-alteration     lung cancer     thyroid cancer     tumor-agnostic therapy     drug    

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Progress in tumor vascular normalization for anticancer therapy: challenges and perspectives

Bingxue Shang, Zhifei Cao, Quansheng Zhou

Frontiers of Medicine 2012, Volume 6, Issue 1,   Pages 67-78 doi: 10.1007/s11684-012-0176-8

Abstract:

Antitumor angiogenic therapy has been shown promising in the treatment of several advanced cancersAlthough the current antiangiogenic drugs reduce the density of tumor blood vessels and result in tumorshrinkage at the early stage of treatment, recent studies have shown that antiangiogenic therapy hashas emerged as a new option for anticancer therapy.vascular normalizing drugs for an effective anticancer therapy.

Keywords： angiogenesis     vasculogenesis     neovascularization     tumor     vasculature     normalization     traditional Chinese medicine    

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Complex interplay between tumor microenvironment and cancer therapy

Minhong Shen, Yibin Kang

Frontiers of Medicine 2018, Volume 12, Issue 4,   Pages 426-439 doi: 10.1007/s11684-018-0663-7

Abstract:

Tumor microenvironment (TME) is comprised of cellular and non-cellular components that exist withinand around the tumor mass.Given the importance of TME in tumor progression and therapy resistance, strategies that remodel TME

Keywords： tumor microenvironment     therapy response     treatment resistance    

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Immunosuppressive tumor microenvironment contributes to tumor progression in diffuse large B-cell lymphomaupon anti-CD19 chimeric antigen receptor T therapy

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%–50therapy failure needs further investigation.functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL.Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansionmetabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy

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

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Multi-target combinatory strategy to overcome tumor immune escape

Frontiers of Medicine 2022, Volume 16, Issue 2,   Pages 208-215 doi: 10.1007/s11684-022-0922-5

Abstract: Immune therapy has become the fourth approach after surgery, chemotherapy, and radiotherapy in cancerIn this work, the author focuses on the combination therapy of multiple immune checkpoints (does notinclude targeted therapy of oncogenes or chemotherapy), introduces the current progression of multipleimmune checkpoints and their related inhibitors, and discusses the advantages of combination therapy

Keywords： immune checkpoints     multi-target     immune escape     immune-related adverse events     combination therapy    

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Palmitoylation of GNAQ/11 is critical for tumor cell proliferation and survival in GNAQ/11-mutant uveal

Frontiers of Medicine 2022, Volume 16, Issue 5,   Pages 784-798 doi: 10.1007/s11684-021-0911-0

Abstract: chemical interference approaches revealed that the loss of GNAQ/11 palmitoylation substantially affected tumor

Keywords： uveal melanoma     mutant GNAQ/11     palmitoylation     BCL2     combination target therapy    

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Platelet membrane-based and tumor-associated platelet- targeted drug delivery systems for cancer therapy

Yinlong Zhang, Guangna Liu, Jingyan Wei, Guangjun Nie

Frontiers of Medicine 2018, Volume 12, Issue 6,   Pages 667-677 doi: 10.1007/s11684-017-0583-y

Abstract: Recent experimental evidence strongly indicates that platelets can also interact with tumor cells by, platelets have been shown to protect circulating cancer cells in blood circulation and to promote tumorhighlights recent progresses in platelet membrane-based drug delivery and unique strategies that target tumor-associatedplatelets for cancer therapy.

Keywords： platelet-mimicking delivery systems     tumor-associated platelets     cancer therapy     EPR effect    

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CAR T cells redirected against tumor-specific antigen glycoforms: can low-sugar antigens guarantee a

Frontiers of Medicine 2022, Volume 16, Issue 3,   Pages 322-338 doi: 10.1007/s11684-021-0901-2

Abstract: However, several clinical trials of solid tumor CAR-T therapies were prematurely terminated, or theyThe simultaneous expression of target antigens by healthy organs and tumor cells is partly responsibleAlongside targeting tumor-specific antigens, targeting the aberrantly glycosylated glycoforms of tumor-associatedantigens can also minimize the off-tumor effects of CAR-T therapies.Tn, T, and sialyl-Tn antigens have been reported to be involved in tumor progression and metastasis,

Keywords： cancer immunotherapy     chimeric antigen receptor     solid tumors     tumor-associated antigen     glycosylation     O-glycans     adoptive cell therapy    

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NADPH oxidase and reactive oxygen species as signaling molecules in carcinogenesis

Gang WANG

Frontiers of Medicine 2009, Volume 3, Issue 1,   Pages 1-7 doi: 10.1007/s11684-009-0018-5

Abstract: messengers, ROS are able to oxidize many targets such as DNA, proteins and lipids, which may be linked with tumorrecent advances in our comprehensive understanding of ROS-linked signaling pathways in regulation of tumor

Keywords： free radicals     tumor     phox     cell proliferation     cancer therapy    

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Antitumor immunity of human SART3 gene vaccine against mouse tumor

HE Yu, YANG Shuhua, LIU Yong, LI Tao

Frontiers of Medicine 2008, Volume 2, Issue 1,   Pages 51-57 doi: 10.1007/s11684-008-0010-5

Abstract: One group was challenged with tumor cells after immunity.Another group was treated with the vaccine after tumor implantation.After vaccination, tumor occurrence and tumor growth speed was reduced.The vaccine also shows activity in tumor treatment.human SART3 (LM8-SART3) which may provide new possibilities in antitumor therapy.

Keywords： antitumor therapy     occurrence     implantation     DNA vaccine     SART3 DNA    

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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 important role in the development of cancer immunotherapy. However, immune-related adverse events often occur because of the enhanced immune response enabled by these agents. Antibiotics are widely applied in clinical treatment, and they are inevitably used in combination with immune checkpoint inhibitors. Clinical practice has revealed that antibiotics can weaken the therapeutic response to immune checkpoint inhibitors. Studies have shown that the gut microbiota is essential for the interaction between immune checkpoint inhibitors and antibiotics, although the exact mechanisms remain unclear. This review focuses on the interactions between immune checkpoint inhibitors and antibiotics, with an in-depth discussion about the mechanisms and therapeutic potential of modulating gut microbiota, as well as other new combination strategies.

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

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Protein phosphatase magnesium-dependent 1δ is a novel tumor marker and target in hepatocellular carcinoma

Zhi Xu,Chunxiang Cao,Haiyan Xia,Shujing Shi,Lingzhi Hong,Xiaowei Wei,Dongying Gu,Jianmin Bian,Zijun Liu,Wenbin Huang,Yixin Zhang,Song He,Nikki Pui-Yue Lee,Jinfei Chen

Frontiers of Medicine 2016, Volume 10, Issue 1,   Pages 52-60 doi: 10.1007/s11684-016-0433-3

Abstract:

Hepatocellular carcinoma (HCC) is a lethal liver malignancy worldwide. In this study, we reported that protein phosphatase magnesium-dependent 1δ (PPM1D) was highly expressed in the majority of HCC cases (approximately 59%) and significantly associated with high serum α-fetoprotein (AFP) level (P= 0.044). Kaplan-Meier and Cox regression data indicated that PPM1D overexpression was an independent predictor of HCC-specific overall survival (HR, 2.799; 95% CI, 1.346–5.818, P = 0.006). Overexpressing PPM1D promoted cell viability and invasion, whereas RNA interference-mediated knockdown of PPM1D inhibited proliferation, invasion, and migration of cultured HCC cells. In addition, PPM1D suppression by small interfering RNA decreased the tumorigenicity of HCC cells in vivo. Overall, results suggest that PPM1D is a potential prognostic marker and therapeutic target for HCC.

Keywords： PPM1D     hepatocellular carcinoma     prognosis     target therapy    

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Heterogeneity of the tumor immune microenvironment and clinical interventions

Frontiers of Medicine 2023, Volume 17, Issue 4,   Pages 617-648 doi: 10.1007/s11684-023-1015-9

Abstract: Heterogeneity of the tumor immune microenvironment and clinical interventions

Keywords： Heterogeneity tumor immune    

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Proteins moonlighting in tumor metabolism and epigenetics

Lei Lv, Qunying Lei

Frontiers of Medicine 2021, Volume 15, Issue 3,   Pages 383-403 doi: 10.1007/s11684-020-0818-1

Abstract: interplay of multiple signaling pathways and restrained by oxygen and nutrient accessibility in the tumorThe signal−moonlighting protein−metabolism axis facilitates the adaptation of tumor cells under varying

Keywords： moonlighting function     tumor metabolism     epigenetics    

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How to judge the association of postmenopausal hormone therapy and the risk of breast cancer

Ling XU

Frontiers of Medicine 2010, Volume 4, Issue 3,   Pages 290-293 doi: 10.1007/s11684-010-0093-7

Abstract: The relevance of postmenopausal hormone therapy (HT) for breast cancer risk has been long debated, althoughThese unanswered questions include: whether HT has a positive impact on breast cancer; whether risks of therapy

Keywords： breast cancer     postmenopausal hormone therapy     unopposed estrogen therapy     combined estrogen-progestin therapy    

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Title Author Date Type Operation

Progress and challenges in RET-targeted cancer therapy

Journal Article

Progress in tumor vascular normalization for anticancer therapy: challenges and perspectives

Bingxue Shang, Zhifei Cao, Quansheng Zhou

Journal Article

Complex interplay between tumor microenvironment and cancer therapy

Minhong Shen, Yibin Kang

Journal Article

Immunosuppressive tumor microenvironment contributes to tumor progression in diffuse large B-cell lymphomaupon anti-CD19 chimeric antigen receptor T therapy

Journal Article

Multi-target combinatory strategy to overcome tumor immune escape

Journal Article

Palmitoylation of GNAQ/11 is critical for tumor cell proliferation and survival in GNAQ/11-mutant uveal

Journal Article

Platelet membrane-based and tumor-associated platelet- targeted drug delivery systems for cancer therapy

Yinlong Zhang, Guangna Liu, Jingyan Wei, Guangjun Nie

Journal Article

CAR T cells redirected against tumor-specific antigen glycoforms: can low-sugar antigens guarantee a

Journal Article

NADPH oxidase and reactive oxygen species as signaling molecules in carcinogenesis

Gang WANG

Journal Article

Antitumor immunity of human SART3 gene vaccine against mouse tumor

HE Yu, YANG Shuhua, LIU Yong, LI Tao

Journal Article

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

Journal Article

Protein phosphatase magnesium-dependent 1δ is a novel tumor marker and target in hepatocellular carcinoma

Zhi Xu,Chunxiang Cao,Haiyan Xia,Shujing Shi,Lingzhi Hong,Xiaowei Wei,Dongying Gu,Jianmin Bian,Zijun Liu,Wenbin Huang,Yixin Zhang,Song He,Nikki Pui-Yue Lee,Jinfei Chen

Journal Article

Heterogeneity of the tumor immune microenvironment and clinical interventions

Journal Article

Proteins moonlighting in tumor metabolism and epigenetics

Lei Lv, Qunying Lei

Journal Article

How to judge the association of postmenopausal hormone therapy and the risk of breast cancer

Ling XU

Journal Article