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病人的肿瘤，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。
前期在美国的课题组研究发现，引发炎症反应并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），目前正在美国德州大学西南医学中心开展II期临床试验：NCT04497584。利用算法模型进行大数据分析，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），经美国课题组的实验验证，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（Nature Cell Biology，2022），揭示了胶质瘤EGFR-TKI临床失败的潜在原因，一项临床联合治疗方案即将推进转化。
课题组研究方向包括：1.免疫应答与炎症反应、代谢产物、酪氨酸激酶等信号通路参与肿瘤靶向与免疫治疗抵抗的分子机制；2. 基于肿瘤临床实践问题，结合整合多组学和分子-细胞-组织-动物-整体的多层次实验，发掘影响肿瘤发生发展及治疗敏感性、患者耐药复发和预后转归的新关键节点；3. 针对候选靶标设计开发新药或再利用已有药物开展个性化防治新方案的临床与产业转化；4. 基于基因组个性化体系差异建立肿瘤精准治疗新理论与大数据算法模型，探索个性化患者-精准药物的匹配治疗模式。
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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