Last update 01 Nov 2024

HER3 x EGF

Last update 01 Nov 2024

Basic Info

Related Targets

HER3EGF

Drugs associated with HER3 x EGF

EN-2642

Target

EGF x HER3

Mechanism

EGF inhibitors [+1]

Active Org.

Enosi Life Sciences Corp.Startup

Originator Org.

Enosi Life Sciences Corp.Startup

Active Indication

Autoimmune Diseases [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with HER3 x EGF

100 Translational Medicine associated with HER3 x EGF

0 Patents (Medical) associated with HER3 x EGF

438

Literatures (Medical) associated with HER3 x EGF

01 Jan 2024·Global Medical Genetics

Expert Consensus on the Diagnosis and Treatment of NRG1/2 Gene Fusion Solid Tumors

Review

Author: Yang, Shengjie ; Wu, Jingxun ; Pan, Weiwei ; Xia, Fan ; Yao, Yanwen ; Li, Bihui ; Li, Jisheng ; Feng, Yue ; Wang, Yina ; Zhang, Jiatao ; Liu, Hongbing ; Sun, Pingli ; Li, Kainan ; Fang, Meiyu ; Huang, Jianhui ; Song, Yong ; Fang, Yong ; Lu, Yuanyuan ; Li, Ziming ; Rao, Chuangzhou ; Meng, Rui ; Li, Yongheng ; Niu, Xiaomin ; Liu, Anwen ; Liu, Weifeng ; Wang, Kai ; Lv, Donglai ; Lv, Tangfeng ; Song, Zhengbo ; Xu, Chunwei ; Wang, Dong ; Wang, Wenxian ; Zhu, Youcai ; Si, Lu ; Zhang, Yinbin ; Lin, Li ; Shi, Xuefei ; Zhang, Yiping ; Zhang, Junping ; Xu, Bingwei ; Wang, Zhaofeng ; Cai, Jing ; Zhang, Rui ; Jin, Gu ; Zhang, Yongchang ; Jiang, Zhansheng ; Wang, Qian ; Xue, Junli ; Wang, Liping ; Xie, Yanru ; Zhong, Wenzhao ; Wang, Hong ; Wu, Lin ; Yao, Wang ; Wei, Jia ; Han, Yu ; Li, Wen ; Min, Lingfeng ; Yu, Jinpu ; Feng, Huijing ; Kang, Jin ; Lin, Xinqing ; Chu, Qian ; Wang, Biyun ; Liu, Aijun ; Zhou, Chengzhi ; Yang, Nong ; Fang, Wenfeng ; Zhou, Jin ; Zhang, Chao ; Cai, Xiuyu ; Ye, Mingxiang ; Ma, Shenglin ; Wu, Fan ; Shi, Lin ; Chen, Xiaofeng ; Jiao, Xiaodong ; Wang, Feng ; Wang, Zhen ; Hao, Yue ; Huang, Long ; Chen, Yu ; Lu, Yuanzhi ; Du, Yingying ; Lin, Gen ; Guo, Hui ; Tang, Chuanhao ; Yuan, Jingping ; Wang, Huijuan ; Qiu, Hong ; Miao, Liyun ; Yu, Zongyang ; Li, Xiaoyan ; Li, Zhongwu ; Pu, Xingxiang ; Wang, Zhijie ; He, Qingqing ; Ou, Juanjuan ; Zhan, Ping ; Xu, Ling ; Lin, Rongbo ; Ge, Rui ; Pang, Fei ; Shen, Yi ; Yuan, Dongmei ; Lv, Dongqing ; Zhang, Shirong ; Chen, Jing ; Liu, Zhefeng ; Dai, Enyong ; Wang, Jiandong ; Li, Yuan ; Zhu, Xixu ; Wang, Lin ; Wang, Guansong ; Wang, Xiaojia ; Wan, Bin ; Zhang, Zhang ; Liu, Jingjing ; Zhu, Zhengfei ; Huang, Jintao

AbstractThe fusion genes NRG1 and NRG2, members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1-positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2. Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.

01 Jul 2023·International Journal of Biological Macromolecules

Pathogenic HER3 dimerization domain mutations create a structural bias towards un-conventional EGFR-HER3 signalling axis in breast cancer

Article

Author: Dey, Pranay ; Gadewal, Nikhil ; De, Abhijit

Among the EGFR family of receptors, HER3 is considered as a pseudo-kinase which primarily interacts with HER2 in presence of heregulin-1β.We identified two hotspot mutations i.e.G284R and D297Y and one double mutant HER2-S310F/HER3-G284R in breast cancer patients.Long term MDS (7.5μs) revealed that HER3-D297Y and HER2-S310F:HER3-G284R do not allow the interaction with HER2 as these mutations cause dramatic conformational changes in its flanking regions.This results in formation of an unstable HER2-WT:HER3-D297Y heterodimer, thereby abrogating the downstream signalling by AKT.We found that His228 and Ser300 of HER3-D297Y form stable interactions with Glu245 and Tyr270 of EGFR-WT, in the presence of either EGF or heregulin-1β.Applying TRIM-ing mediated direct knockdown of endogenous EGFR protein, specificity of the unconventional EGFR:HER3-D297Y interaction was validated.Due to this unusual ligand mediated interaction, cancer cells were found susceptible to EGFR targeted therapeutics i.e.Gefitinib and Erlotinib.Further, in TCGA anal., BC patients harbouring HER3-D297Y mutation showed increased p-EGFR levels as compared to the patients harbouring HER3-WT and HER3-G284R mutations.For the first time, this comprehensive study showed the importance of specific hotspot mutations in HER3 dimerization domain can defy the Trastuzumab therapy, rather cells become susceptible to the EGFR inhibitors.

28 May 2023·Current oncology (Toronto, Ont.)

Afatinib for the Treatment of NSCLC with Uncommon EGFR Mutations: A Narrative Review.

Review

Author: Fang, Tingwen ; Liu, Jingwen ; Jiang, Yingying ; Lu, Kaihua ; Xiang, Yan ; Fang, Xiaoxu

Afatinib, the world's first irreversible ErbB family (containing four different cancer cell epidermal growth factor receptors, including EGFR, HER2, ErbB3, and ErbB4) inhibitor, is a second-generation oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). It can be used as a first-line treatment for locally advanced or metastatic non-small-cell lung cancer (NSCLC) with an EGFR-sensitive mutation or for patients with locally advanced or metastatic squamous lung cancer whose disease progresses during or after platinum-containing chemotherapy. Currently, with the use of third-generation EGFR-TKIs, afatinib is no longer clinically indicated as the first choice for patients with NSCLC who have EGFR-sensitive mutations. However, afatinib showed a considerable inhibitory effect in NSCLC patients with uncommon EGFR mutations (G719X, S768I, and L861Q) according to a combined post hoc analysis of the LUX-Lung2/3/6 trials. With the development of genetic testing technology, the detection rate of uncommon EGFR mutations is increasing. The aim of this paper is to describe in detail the sensitivity of rare EGFR mutations to afatinib and to provide information and a reference for those suffering from advanced NSCLC who have uncommon EGFR mutations.

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