Epidermal growth factor receptor mutations in breast Cancer: Therapeutic challenges and way forward.

IF 4.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Swathi R Shetty, Trisha Kar, Amitava Das
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引用次数: 0

Abstract

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) that is upregulated in aggressive triple-negative breast cancer (TNBC). Ligands such as EGF, TGF-α, epigen, and amphiregulin activate the auto-phosphorylation activity of tyrosine residues on EGFR, which regulates the growth, proliferation, adhesion, migration, and survival of cancer cells. Our prior studies depicted that inhibition of EGFR modulates the chemosensitivity in breast cancer stem cells and, thus, serves as a potent therapeutic target in breast cancer. Small-molecule tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs) specifically targeting EGFR have been clinically approved for breast cancer treatment. However, intrinsic and acquired resistance generated due to EGFR mutations limits the applications of designed EGFR-TKIs in breast cancer patients. This review highlights the therapeutic approaches, and the challenges encountered in targeting EGFR-specific mutations. It suggests the need to develop more advanced higher-generation inhibitors for use in combinatorial therapy along with chemo-or-immune therapeutics in clinics as a breast cancer treatment strategy against relapse of the disease.

乳腺癌中的表皮生长因子受体突变:治疗挑战与前进之路。
表皮生长因子受体(EGFR)是一种受体酪氨酸激酶(RTK),在侵袭性三阴性乳腺癌(TNBC)中上调。配体(如表皮生长因子、表皮生长因子-α、表皮生长因子和表皮生长因子)可激活表皮生长因子受体上酪氨酸残基的自身磷酸化活性,从而调节癌细胞的生长、增殖、粘附、迁移和存活。我们之前的研究表明,抑制表皮生长因子受体可调节乳腺癌干细胞的化疗敏感性,从而成为乳腺癌的有效治疗靶点。专门针对表皮生长因子受体的小分子酪氨酸激酶抑制剂(TKIs)和单克隆抗体(mAbs)已被临床批准用于乳腺癌治疗。然而,由于表皮生长因子受体(EGFR)突变产生的内在和获得性耐药性限制了设计的 EGFR-TKIs 在乳腺癌患者中的应用。本综述重点介绍了针对表皮生长因子受体特异性突变的治疗方法和所遇到的挑战。这表明有必要开发更先进的高世代抑制剂,与化疗或免疫疗法一起用于临床中的组合疗法,作为防止疾病复发的乳腺癌治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Bioorganic Chemistry
Bioorganic Chemistry 生物-生化与分子生物学
CiteScore
9.70
自引率
3.90%
发文量
679
审稿时长
31 days
期刊介绍: Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.
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