Henson Elizabeth, Chen Yongqiang, Gibson Spencer
Research Institute in Oncology and Hematology, CancerCare Manitoba, 675 McDermot Ave., Winnipeg, MB R3E 0V9, Canada.
Department of Biochemistry and Medical Genetics, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0V9, Canada.
Cancers (Basel). 2017 Mar 24;9(4):27. doi: 10.3390/cancers9040027.
The epidermal growth factor receptor (EGFR) signaling pathways are altered in many cancers contributing to increased cell survival. These alterations are caused mainly through increased expression or mutation of EGFR family members EGFR, ErbB2, ErbB3, and ErbB4. These receptors have been successfully targeted for cancer therapy. Specifically, a monoclonal antibody against ErbB2, trastuzumab, and a tyrosine kinase inhibitor against EGFR, gefitinib, have improved the survival of breast and lung cancer patients. Unfortunately, cancer patients frequently become resistant to these inhibitors. This has led to investigating how EGFR can contribute to cell survival and how cancer cells can overcome inhibition of its signaling. Indeed, it is coming into focus that EGFR signaling goes beyond a single signal triggering cell proliferation and survival and is a sensor that regulates the cell's response to microenvironmental stresses such as hypoxia. It acts as a switch that modulates the ability of cancer cells to survive. Autophagy is a process of self-digestion that is inhibited by EGFR allowing cancer cells to survive under stresses that would normally cause death and become resistant to chemotherapy. Inhibiting EGFR signaling allows autophagy to contribute to cell death. This gives new opportunities to develop novel therapeutic strategies to treat cancers that rely on EGFR signaling networks and autophagy. In this review, we summarize the current understanding of EGFR family member regulation of autophagy in cancer cells and how new therapeutic strategies could be developed to overcome drug resistance.
表皮生长因子受体（EGFR）信号通路在许多癌症中发生改变，导致细胞存活率增加。这些改变主要是通过EGFR家族成员EGFR、ErbB2、ErbB3和ErbB4的表达增加或突变引起的。这些受体已成功成为癌症治疗的靶点。具体而言，一种针对ErbB2的单克隆抗体曲妥珠单抗和一种针对EGFR的酪氨酸激酶抑制剂吉非替尼，提高了乳腺癌和肺癌患者的存活率。不幸的是，癌症患者经常对这些抑制剂产生耐药性。这促使人们研究EGFR如何促进细胞存活以及癌细胞如何克服其信号传导的抑制。事实上，越来越受到关注的是，EGFR信号传导不仅仅是触发细胞增殖和存活的单一信号，而且是一种调节细胞对缺氧等微环境应激反应的传感器。它充当调节癌细胞存活能力的开关。自噬是一种自我消化过程，被EGFR抑制，使癌细胞能够在通常会导致死亡的应激条件下存活并对化疗产生耐药性。抑制EGFR信号传导会使自噬导致细胞死亡。这为开发新的治疗策略提供了新机会，以治疗依赖EGFR信号网络和自噬的癌症。在这篇综述中，我们总结了目前对癌细胞中EGFR家族成员对自噬的调节的理解，以及如何开发新的治疗策略来克服耐药性。
