MD安德森研究显示关键酶连接到治疗性致命的肺癌

Two existing therapies may have potential for further study in treatment of EGFR-mutant non-small cell lung cancers

MD安德森新闻Release December 10, 2018

乐动体育LDsports中国在研究人员得克萨斯大学MD安德森癌症中心的大学have identified a link between an enzyme tied to cancer formation and therapy resistance in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). They believe two existing therapies may hold promise for clinical studies for this deadly and common lung cancer for which relapse often occurs within one year following treatment.

The study revealed a unique “addiction” between the enzyme protein kinase C delta (PKCδ) found in NSCLC tumors and standard-of-care treatment called EGFR tyrosine kinase inhibitors (TKIs). Based on mouse and human tissue samples, this link allows PKCδ to lessen TKIs’ ability to forestall cancer. Findings were published in the Dec. 10 online issue of Cancer Cell.

Approximately 160,000 people in the U.S. are diagnosed with NSCLC each year, and roughly 15,000 have metastatic disease with EGFR mutations.

“抗表皮生长因子受体TKIs的多个方法been identified in EGFR-mutant non-small cell lung cancer, but resistance to treatment remains a major challenge,” said洪明奇，博士，主席分子与细胞肿瘤。“我们的研究鉴定PKCδ如通过对EGFR TKIs抗性的多种方法共享的公共介体和它显著演示PKCδ的抑制促进EGFR TKI中诱导抗肿瘤的消退与EGFR突变”。

EGFR是属于家族称为受体酪氨酸激酶（RTKs）在NSCLC频繁突变引起的细胞变化，包括增强细胞生长，肿瘤形成和转移的蛋白质。TKIs的EGFR中断细胞信号传导，抑制肿瘤的发展。然而治疗的肿瘤最终会发展抗性由于统称为肿瘤的异质性，其包括EGFR的额外的突变和/或其它RTK的过表达多种机制。

TKIs的针对特定耐药机制的新一代已经被开发，这帮助患者存活数月，但复发仍然出现和患者最终被留下没有治疗方案。为了克服肿瘤的异质性，这是至关重要的，以确定一个共同的介体，其中，封端时，可以提供有效的治疗，红加入。

的小组观察到高水平的PKCδ活化在荷瘤小鼠和患者的组织样本，揭示PKCδ为TKI性的要求，并且与下面的TKI治疗恶化的无进展生存相关联的。

The team discovered a combination of two therapies studied in mice, gefitinib and sotrastaurin, appear to be effective as a potential therapy strategy for EGFR-mutant NSCLC TKI resistance. Gefitinib is an FDA-approved TKI for EGFR-mutant NSCLC, while sotrastaurin is approved for use in clinical trials in cancer and other diseases.

“Since gefitinib has received regulatory approval in NSCLC patients and sotrastaurin is available for clinical studies, the combination could be readily tested in clinical trials, especially for patients whose tumor has developed TKI resistance,” said Hung. “It is our hope that new therapies that could result from such studies may be of benefit to patients who have not responded to existing treatments.”

MD安德森的团队成员包括培志利，博士;岳 - 阜丰，医学博士;裕仁山口，D.V.M.，博士;伟扬王，博士;绚香，医学博士，博士;堡镇柯，B.S;Weiha下，医学博士;Yongkun Wi,医学博士,博士;正雨咋博士;Yan Wang, Ph.D.; Lei Nie, Ph.D.; Junwei Hou, Ph.D.; Chun-Te Chen, Ph.D.; Longfei Huo, Ph.D.; Wen-Hao Yang, Ph.D.; Rong Deng, Ph.D.; Katusuya Nakai, M.D.; Yi-Hsin Hsu, Ph.D.; Shi-Shin Chang, Ph.D.; Tai-Jan Chiu, M.D.; Jun Tang, M.D. and Jennifer Hsu, Ph.D., all of the Department of Molecular and Cellular Oncology; Ran Zhang, Ph.D., Li Wang, Ph.D., and Bingliang Fang, M.D., Ph.D., of Thoracic and Cardiovascular Surgery.

Other participating institutions include: Chang Gung Memorial Hospital, Saint Paul’s Hospital, and Chang Gung University College of Medicine, Taoyuan, Taiwan; Harbin Medical University Cancer Hospital, Heilongjiang, China; China Medical University and National Chung-Hsing University, Taichung, Taiwan; Sun Yat-sen University, Guangzhou, China; Chang Gung University College of Medicine, Kaohsiung, Taiwan; Langone Medical Center, New York; and Dana-Farber Cancer Institute, Boston.