Xiangyan Jiang
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Xiangyan Jiang has a total of 16 co-authors. Here are the top co-authors by number of shared publications:
- Baoyuan Tang
The Second Clinical Medical College, Lanzhou University, Lanzhou, People’s Republic of China
1 shared publication - Bo Long
The Department of General Surgery, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, People’s Republic of China
1 shared publication - Huiming Zhao
The Second Clinical Medical College, Lanzhou University, Lanzhou, People’s Republic of China
1 shared publication - Huinian Zhou
The Department of General Surgery, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, People’s Republic of China
1 shared publication - Long Qin
Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, People’s Republic of China
1 shared publication - Qianlin Gu
The Second Clinical Medical College, Lanzhou University, Lanzhou, People’s Republic of China
1 shared publication
Latest Publications
- 6 November 2026
- Published by American Association for Cancer Research (AACR) in Cancer Research
- p. OF1-OF17
Nonkinase-Orchestrated VEGFR2–ERK Signaling Is a Dependency and Pharmacologic Target for Antiangiogenic Immunotherapy
Antiangiogenic immunotherapy represents a promising cancer treatment strategy. However, the efficacy of this combination approach is hindered by inadequate vascular normalization. Although the fundamental role of canonical kinase-centric VEGFR–ERK signaling in angiogenesis is appreciated, the kinase-centric model overlooks nonkinase components of the pathway, such as adapters, scaffolds, and other nonkinase interacting proteins, that could affect the response to antiangiogenic therapy. In this study, employing an ERK kinase translocation reporter and CRISPR-Pool SAM activation screening, we revealed that the nonkinase SHC–SHCBP1 complex governed VEGFR2–ERK activity and was a dependency for aberrant tumor angiogenesis. Genetic knockout of Shcbp1 in mice sensitized tumors to VEGFR2 inhibition, preventing excessive angiogenesis, normalizing tumor vasculature, and reprogramming the immunosuppressive microenvironment to enhance immunotherapy efficacy. Mechanistically, ERK directly formed a complex with SHC and SHCBP1. Upon VEGF stimulation, active VEGFR2 recruited SHC to liberate the SHCBP1–ERK complex. SHCBP1 then triggered ERK hyperactivation by promoting ERK phosphorylation and nuclear localization signal-importin–dependent nuclear shuttling, creating a feedforward loop to exacerbate pathologic angiogenesis. Clinically, SHCBP1 overexpression negatively correlated with vascular normalization and antiangiogenic immunotherapy response in patients. High-throughput screening led to the development of MS1943, an inhibitor blocking SHCBP1–ERK nuclear transport. Combined with the VEGFR2 inhibitor rivoceranib and anti–PD-1, MS1943 demonstrated antitumor activity against immunotherapy-resistant preclinical models, with favorable tolerance. These findings define a nonkinase-governed VEGFR2–ERK signaling pathway as a targetable dependency for tumor angiogenesis, offering the foundation for alternative antiangiogenic immunotherapy strategies. Significance: The VEGFR2–ERK pathway is governed by the nonkinase SHC–SHCBP1 complex, which operates beyond the kinase-centric cascade and can be targeted to normalize tumor vessels and enhance immunotherapy efficacy.
- 6 November 2026
- Published by American Association for Cancer Research (AACR) in Cancer Research
- p. OF1-OF17
Nonkinase-Orchestrated VEGFR2–ERK Signaling Is a Dependency and Pharmacologic Target for Antiangiogenic Immunotherapy
Antiangiogenic immunotherapy represents a promising cancer treatment strategy. However, the efficacy of this combination approach is hindered by inadequate vascular normalization. Although the fundamental role of canonical kinase-centric VEGFR–ERK signaling in angiogenesis is appreciated, the kinase-centric model overlooks nonkinase components of the pathway, such as adapters, scaffolds, and other nonkinase interacting proteins, that could affect the response to antiangiogenic therapy. In this study, employing an ERK kinase translocation reporter and CRISPR-Pool SAM activation screening, we revealed that the nonkinase SHC–SHCBP1 complex governed VEGFR2–ERK activity and was a dependency for aberrant tumor angiogenesis. Genetic knockout of Shcbp1 in mice sensitized tumors to VEGFR2 inhibition, preventing excessive angiogenesis, normalizing tumor vasculature, and reprogramming the immunosuppressive microenvironment to enhance immunotherapy efficacy. Mechanistically, ERK directly formed a complex with SHC and SHCBP1. Upon VEGF stimulation, active VEGFR2 recruited SHC to liberate the SHCBP1–ERK complex. SHCBP1 then triggered ERK hyperactivation by promoting ERK phosphorylation and nuclear localization signal-importin–dependent nuclear shuttling, creating a feedforward loop to exacerbate pathologic angiogenesis. Clinically, SHCBP1 overexpression negatively correlated with vascular normalization and antiangiogenic immunotherapy response in patients. High-throughput screening led to the development of MS1943, an inhibitor blocking SHCBP1–ERK nuclear transport. Combined with the VEGFR2 inhibitor rivoceranib and anti–PD-1, MS1943 demonstrated antitumor activity against immunotherapy-resistant preclinical models, with favorable tolerance. These findings define a nonkinase-governed VEGFR2–ERK signaling pathway as a targetable dependency for tumor angiogenesis, offering the foundation for alternative antiangiogenic immunotherapy strategies. Significance: The VEGFR2–ERK pathway is governed by the nonkinase SHC–SHCBP1 complex, which operates beyond the kinase-centric cascade and can be targeted to normalize tumor vessels and enhance immunotherapy efficacy.