以表皮生长因子EGFR为代表的受体酪氨酸激酶（RTK）癌基因信号异常与肿瘤发生发展及治疗抵抗高度相关。当前肿瘤精准治疗正面临两大挑战：（1）靶向治疗药物虽然对癌基因异常肿瘤早期效果显著，但最终仍不可避免发生获得性耐药，并且野生型原发性耐药；（2）免疫检查点药物虽能持续抑制部分实体肿瘤，但适应症标志物不能确定，且往往对适用靶向治疗的如RTK异常肿瘤疗效欠佳。
前期在美国课题组的研究发现，引发炎症反应并能杀死肿瘤的肿瘤坏死因子TNF也能促进非小细胞肺癌和脑神经胶质瘤的耐药生存（Gong et al. Journal of Clinical Investigation 2018，Guo et al. Nature Neuroscience 2017，Guo et al. Neuro-Oncology 2019，Gong et al. Neoplasia 2021），此外，促肿瘤免疫的天然免疫通路相关的I型干扰素基因，在肿瘤靶向治疗中却扮演着诱导治疗抵抗的角色并影响PDL1相关的免疫治疗（Gong et al. Nature Cancer 2020）。更为重要的是，一种临床常用且强效的免疫抑制剂和消炎药——糖皮质激素——被发现具有广谱且强力的耐药通路阻断效果（Gong et al. Nature Communications, 2021），正在美国德州大学西南医学中心开展II期临床试验：NCT04497584（2020-2024）。另外，利用一种新算法模型分析胶质瘤数据，提示EGFR配体依赖的过度功能活化可将EGFR受体功能从促进肿瘤生长为主（grow）转变为抑制肿瘤侵袭优先（go），经课题组实验验证，发现了脑神经胶质瘤对靶向EGFR治疗原发性耐药的分子机制（Guo et al. Nature Cell Biology，2022），揭示了胶质瘤EGFR-TKI临床失败的可能原因，相关III期临床试验NCT05326464（2022-2026）正在开展。
目前，本人负责的独立课题组研究兴趣主要从肿瘤细胞的视角出发，了解它们如何生存发展并抵御内外环境中的各种不利因素，以弱克强，反侮为病，从对机制的探索中寻找攻克癌症的新策略。研究对象为肺癌、乳腺癌、肝癌等国内高发病的癌种。
具体内容包括：1）免疫、炎症、代谢、神经等信号通路介导的酪氨酸激酶靶向药物治疗抵抗的分子机制；2）围绕临床问题，结合整合组学与实验研究，挖掘影响肿瘤治疗响应、患者预后转归的肿瘤染色体变异相关的新型调控模式与治疗靶点；3）基于数据预测算法，发现个性化患者-精准药物相匹配的联合治疗新方案，并推动临床转化。
承担本科生课程《病原学与免疫学前沿技术》；参与本科生课程《基础医学导论》《医学前沿进展》《损伤与反应》《基础医学实验技术》，以及研究生课程《医学免疫学》《免疫学前沿进展》《细胞与分子生物学》《免疫新进展》的教学。
Ke Gong, Gao Guo, Nicole A. Beckley, Xiaoyao Yang, Yue Zhang, David E. Gerber, John D. Minna, Sandeep Burma, Dawen Zhao, Esra A. Akbay & Amyn A. Habib* Comprehensive targeting of resistance to inhibition of RTK signaling pathways by using glucocorticoids. Nature Communications. 2021 12:7014 (Processed to a Phase II Clinical Trial: NCT04497584)
Ke Gong, Gao Guo, Nishah Panchani, Matthew E. Bender, David E. Gerber, John D. Minna, Farjana Fattah, Boning Gao, Michael Peyton, Kemp Kernstine, Bipasha Mukherjee, Sandeep Burma, Cheng-Ming Chiang, Shanrong Zhang, Adwait Amod Sathe, Chao Xing, Kathryn H. Dao, Dawen Zhao, Esra A. Akbay, and Amyn A. Habib* EGFR inhibition triggers an adaptive response by co-opting antiviral signaling pathways in lung cancer. Nature Cancer. 2020 1(4): 394–409. （Highlighted by Nature Cancer，Cancer Discovery and Nature Reviews Cancer)
Ke Gong#, Gao Guo#, David E Gerber, Boning Gao, Michael Peyton, Chun Huang, John D Minna, Kimmo J Hatanpaa, Kemp Kernstine, Ling Cai, Yang Xie, Hong Zhu, Farjana J Fattah, Shanrong Zhang, Masaya Takahashi, Bipasha Mukherjee, Sandeep Burma, Jonathan Dowell, Kathryn Dao, Vassiliki A Papadimitrakopoulou, Victor Olivas, Trever G Bivona, Dawen Zhao, Amyn A Habib*. TNF-driven adaptive response mediates resistance to EGFR inhibition in lung cancer. Journal of Clinical Investigation. 2018 128(6):2500-2518 #Co-first author
Ke Gong*, Gao Guo, Nicole Beckley, Yue Zhang, Xiaoyao Yang, Mishu Sharma, Amyn A.Habib* Tumor necrosis factor in lung cancer: Complex roles in biology and resistance to treatment. Neoplasia. 2021 23(2):189-196
Zhi-Hao Wang#, Ke Gong#, Xia Liu, Zhentao Zhang, Xiaoou Sun, Zheng Wei, Shan Yu, Fredric P Manfredsson, Ivette Sandoval, Peter Johnson, Jianping Jia, Jian-Zhi Wang, and Keqiang Ye* C/EBPβ regulates Delta-secretase expression and mediates pathogenesis in mouse models of Alzheimer’s Disease. Nature Communications. 2018 9(1):1784 #Co-first author
Ke Gong, Zhenxing Zhang, Yicheng Chen, Hong-Bing Shu, Wenhua Li* Extracellular signal-regulated kinase, receptor interacting protein, and reactive oxygen species regulate shikonin-induced autophagy in human hepatocellular carcinoma. European Journal of Pharmacology. 2014 738:142-52
Ke Gong#, Chao Chen#, Yao Zhan, Yan Chen, Zebo Huang, Wenhua Li*. Autophagy-related gene 7 (Atg7) and reactive oxygen species (ROS)/extracellular-signal-regulated kinase (ERK) regulate tetrandrine-inducedautophagy in human hepatocellular carcinoma. Journal of Biological Chemistry.2012, 287:35576-88 #Co-first author
Ke Gong, Jia Xie, Hong Yi, Wenhua Li*. CS055 (Chidamide/HBI-8000), a novel histone deacetylase inhibitor, induces G1-arrest, ROS-dependent apoptosis and differentiation in human leukemia cells. Biochemical Journal. 2012, 443:735-46
Ke Gong, Wenhua Li* Shikonin, a Chinese plant-derived naphthoquinone, induces apoptosis in hepatocellular carcinoma cells through reactive oxygen species: A potential new treatment for hepatocellular carcinoma. Free Radical Biology and Medicine. 2011, 51:2259-71.
Gao Guo, Ke Gong, Nicole Beckley, Yue Zhang, Xiaoyao Yang, Rati Chkheidze, Kimmo J Hatanpaa, Tomas Garzon-Muvdi, Prasad Koduru, Arifa Nayab, Jennifer Jenks, Adwait Amod Sathe, Yan Liu, Chao Xing, Shwu-Yuan Wu, Cheng-Ming Chiang, Bipasha Mukherjee, Sandeep Burma, Bryan Wohlfeld, Toral Patel, Bruce Mickey, Kalil Abdullah, Michael Youssef, Edward Pan, David E Gerber, Shulan Tian, Jann N Sarkaria, Samuel K McBrayer, Dawen Zhao, Amyn A Habib* EGFR ligand shifts the role of EGFR from oncogene to tumour suppressor in EGFR-amplified glioblastoma by suppressing invasion through BIN3 upregulation. Nature Cell Biology. 2022 Aug 1
Guo G, Gong K, Puliyapaddamba VT, Pan E, Mukherjee B, Damanwalla Z, Bharia S, Hatanpaa KJ, Zhao D, Burma S, and Habib AA* Efficacy of EGFR plus TNF inhibition in a preclinical model of temozolomide-resistant glioblastoma. Neuro-Oncology. 2019 Nov 8;10(1):5108
Guo G, Gong K, Ali S, Ali N, Shallwani S, Hatanpaa KJ, Pan E, Mickey B, Burma S, Wang DH, Kesari S, Sarkaria JN, Zhao D, Habib AA* A TNF-JNK-Axl-ERK signaling axis mediates primary resistance to EGFR inhibition in glioblastoma. Nature Neuroscience. 2017 Aug;20(8):1074-1084
Guo G, Gong K, Habib AA* Analysis of Constitutive EGFR Signaling Regulating IRF3 Transcriptional Activity in Cancer Cells. Methods in Molecular Biology. 2017 1652 183-189
Guo G, Gong K, Wohlfeld B, Hatanpaa KJ, Zhao D, Habib AA* Ligand-Independent EGFR Signaling. Cancer Research. 2015 Sep 1;75(17):3436-41
Song Y, Gong K, Yan H, Hong W, Wang L, Wu Y, Li W*, Li W*, Cao Z* Sj7170, a unique dual-function peptide with a specific α-chymotrypsin inhibitory activity and a potent tumor-activating effect from scorpion venom. Journal of Biological Chemistry 2014 289 (17), 11667-11680
Zhan Y, Gong K, Chen C, Wang H, Li W* P38 MAP kinase functions as a switch in MS-275-induced reactive oxygen species-dependent autophagy and apoptosis in human colon cancer cells. Free Radical Biology and Medicine 2012 53 (3), 532-543
Liu C, Gong K, Mao X, Li W* Tetrandrine induces apoptosis by activating reactive oxygen species and repressing Akt activity in human hepatocellular carcinoma. International Journal of Cancer 2011 129 (6), 1519-1531
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