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Expression of Gli1 in the hedgehog signaling pathway and breast cancer recurrence

Chinese Journal of Cancer Research 2012年第4期24卷 257-258页

作者： naoko takebe Sally Hunsberger Sherry X.Yang Cancer Therapy Evaluation Program Bioinformatics Research Branch National Clinical Target Validation Laboratory Division of Cancer Treatment and DiagnosisNational Cancer InstituteNational Institutes of HealthUSA

The hedgehog （Hh） signaling pathway plays an essential role in the embryonic development and homeostasis of diverse adult tissues, and its deregulation has been implicated in the tumorigenesis and metastasis of various malignancies including breast cancer. Aberrant activation of the Hh pathway includes the following mechanisms：（I） Hh ligand-independent mechanism - Loss of function mutations in the Hh receptor Patched 1 （PTCH1） or gain of function mutations in the Smoothened （SMO） lead to constitutive activation of this pathway; （II） Autocrine signaling- Ith ligand produced by tumor cells stimulates the Hh signaling in tumor cells; （III） Paracrine signaling - tumor cell produced-Hh ligand activates stromal and endothelial cells that produce growth factors in microenvironment for supporting tumor growth and survival; and （IV） Reverse paracrine signaling - Hh ligand produced by stromal cells support tumor growth and survival. Upon the pathway activation, the Gli transcription factors, effectors of the Hh signaling, activate or inhibit transcription by binding to their responsive genes and interacting with the transcriptional complex. The Gli transcription factor family includes Glil, Gli2, and Gli3 （1）. Glil is a transcriptional activator whose expression has been recognized as an activation state of the Hh signaling pathway, Gli2 is either an activator or repressor, and Gli3 is a strong repressor of transcriptional activities. To date, a ligand-dependent autocrine model of activating the Hh signaling has been described in breast cancer, and both an autocrine and paracrine mechanisms in colorectal cancer, pancreatic cancer and prostate cancer （2,3）. Notably, a ligand-independent mechanism （mutationsin PTCHI and SMO） of the signaling has been well demonstrated in basal cell carcinoma and medulloblastoma （4,5）.

关键词： cell Expression of Gli1 in the hedgehog signaling pathway and breast cancer recurrence

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A review of mechanisms of resistance to immune checkpoint inhibitors and potential strategies for therapy

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Cancer Drug Resistance 2020年第3期3卷 252-275页

作者： Yu Fujiwara Arjun Mittra Abdul Rafeh Naqash naoko takebe Developmental Therapeutics Clinic Division of Cancer Treatment and DiagnosisNational Cancer InstituteBethesdaMD 20892USA. Department of Medical Oncology The Cancer Institute Hospital of Japanese Foundation for Cancer ResearchTokyo 1358550Japan Department of Medical Oncology Musashino Red Cross HospitalTokyo 1800023Japan

Immune checkpoint inhibitors(ICIs)have revolutionized the treatment of cancer over the last decade,bringing about a paradigm shift in systemic cancer therapy away from traditional cytotoxic and targeted *** some patients have dramatic treatment responses,it is sobering to note that most tumors are either resistant at the outset,or develop resistance after initial response.A major area of translational and clinical research is in identifying therapeutic strategies to overcome resistance to *** have performed an in-depth review of the different mechanisms of resistance and potential avenues to overcome resistance through rationally designed combination treatment with ICIs.

关键词： Immunotherapy resistance tumor microenvironment PD-1 PD-L1 CTLA-4

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