Review
Biochemistry & Molecular Biology
Xiyin Li, Lina Zhao, Ceshi Chen, Jianyun Nie, Baowei Jiao
Summary: This review summarizes the regulatory mechanisms of EGFR protein expression in breast cancer cells, including mutations, amplification, endocytic dysfunction, recycling acceleration, and degradation disorders. Potential therapeutic strategies targeting EGFR, such as reducing protein expression, precise clearance of target proteins, and inhibiting non-EGFR signaling pathways, are also discussed.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Article
Biochemistry & Molecular Biology
Shiqi Ma, Lu Zhang, Yuan Ren, Wei Dai, Tingqing Chen, Liping Luo, Juan Zeng, Kun Mi, Jinyi Lang, Bangrong Cao
Summary: This study revealed the impact of EREG on EGFR-TKI sensitivity and its mechanisms in NSCLC, suggesting macrophage-produced EREG as a potential novel regulator and biomarker for EGFR-TKI therapy in NSCLC.
Article
Biochemistry & Molecular Biology
Peeyush N. Goel, Hongtao Zhang, Ramachandran Murali, Cai Zheng, Mei Q. Ji, Angelica Patterson, Payal Grover, Mark Greene
Summary: Mutations in the EGFR gene are common in NSCLC, with the L858R mutation in Exon 21 being the most prevalent. While targeted therapies like monoclonal antibodies and TKIs have shown efficacy, resistance eventually develops due to mutations such as T790M and C797S. A third-generation TKI, AZD9291, has high affinity for these mutations, but recent research suggests the emergence of resistance due to the EGFR (C797S) mutation. Additionally, erbB2 amplification is another significant mechanism of resistance. A small kinase inhibitor, ER121, has been developed to target these mutations and has shown promising inhibitory activity in mutant EGFR and amplified ErbB2 cancers.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Oncology
Elena Levantini, Giorgia Maroni, Marzia Del Re, Daniel G. Tenen
Summary: EGFR plays an important role in maintaining epithelial tissues, but when its signaling is altered, it becomes a major regulator of epithelial transformation and is one of the most studied tyrosine kinase receptors involved in neoplasia worldwide. EGFR-targeted therapies have revolutionized cancer treatment, but the dream of turning solid tumors into chronic diseases remains unfulfilled.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Juliann Chmielecki, Tony Mok, Yi-Long Wu, Ji-Youn Han, Myung-Ju Ahn, Suresh S. Ramalingam, Thomas John, Isamu Okamoto, James Chih-Hsin Yang, Frances A. Shepherd, Krishna C. Bulusu, Gianluca Laus, Barbara Collins, J. Carl Barrett, Ryan J. Hartmaier, Vassiliki Papadimitrakopoulou
Summary: The third-generation EGFR tyrosine kinase inhibitor osimertinib improves progression-free survival compared to platinum-doublet chemotherapy in patients with advanced NSCLC carrying EGFR T790M mutation. In this study, the authors used next-generation sequencing to evaluate the potential mechanisms of acquired resistance to osimertinib in patients from the AURA3 trial. Some patients had undetectable plasma EGFR T790M at disease progression and/or treatment discontinuation.
NATURE COMMUNICATIONS
(2023)
Review
Medicine, Research & Experimental
Jiahui Fu, Jin Zhang, Xiya Chen, Zhiying Liu, Xuetao Yang, Zhendan He, Yue Hao, Bo Liu, Dahong Yao
Summary: ATPase family AAA domain-containing protein 2 (ATAD2) is a new oncogene closely associated with epigenetic modifications in human cancers. It functions as a coactivator of transcription factors and regulates the expression of downstream oncogenes or tumor suppressors. The dominant structure of ATAD2 makes it a potential therapeutic target in cancer, and small-molecule inhibitors have been discovered. This review focuses on summarizing the structural features and biological functions of ATAD2 as well as the existing small-molecule inhibitors targeting ATAD2 for potential cancer therapy.
Article
Medicine, Research & Experimental
Shalini Mani, Geeta Swargiary, Sakshi Tyagi, Manisha Singh, Niraj Kumar Jha, Keshav K. Singh
Summary: Nanotechnology-based approaches offer incredible potential in cancer therapeutics due to their higher target specificity, demonstrating a potential and efficient way to target mitochondria of cancer cells for improved survival rates of cancer patients.
Review
Oncology
Qian Wang, Anqi Zeng, Min Zhu, Linjiang Song
Summary: Globally, the incidence and mortality rates of lung cancer are increasing year by year. The EGFR pathway can promote the survival and proliferation of tumor cells, while the VEGF pathway promotes tumor growth. EGFR activation in NSCLC can enhance VEGF expression, leading to resistance to EGFR inhibitors. To overcome this, dual inhibition of the EGFR-VEGF pathway has become the preferred method. Dual inhibition not only overcomes resistance to EGFR inhibitors but also significantly increases progression-free survival in NSCLC patients.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2023)
Article
Medicine, Research & Experimental
Yanli Bi, Xiaoyu Chen, Bajin Wei, Linchen Wang, Longyuan Gong, Haomin Li, Xiufang Xiong, Yongchao Zhao
Summary: DEPTOR interacts with and stabilizes ErbB2, promoting proliferation and survival of ErbB2-positive breast cancer cells. Overexpression of DEPTOR is correlated with poorer patient survival, and the membrane localization of DEPTOR may contribute to the oncogenic characteristics of ErbB2.
Review
Pharmacology & Pharmacy
Woo Jung Sung, Dohyang Kim, Anlin Zhu, Namki Cho, Hee Min Yoo, Ji Heon Noh, Kyoung Mi Kim, Hyun-Su Lee, Jaewoo Hong
Summary: Targeting EGFR-mediated tumors involves the use of tyrosine kinase inhibitors, anti-EGFR monoclonal antibodies, or their combination with chemotherapy or immune checkpoint inhibitors. However, there are challenges in terms of adverse effects and limited efficacy. A potential new approach is targeting the lysosome to overcome EGFR-mediated cancers.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Oncology
Nannan Wang, Yuepeng Cao, Chengshuai Si, Peng Shao, Guoqing Su, Ke Wang, Jun Bao, Liu Yang
Summary: This article discusses the molecular biology of ERBB2 in metastatic CRC and targeted therapeutic strategies, emphasizing the importance of its therapeutic role, while also highlighting some potential treatment approaches and clinical trials.
Review
Oncology
Blessie Elizabeth Nelson, Jacob J. Adashek, Steven H. Lin, Vivek Subbiah
Summary: With the development of immune-based therapies, the abscopal phenomenon has gained significant attention. Collaboration among radiation oncologists, oncologists and immunologists has increased, leading to exploration of various methods to induce the abscopal effect. However, further prospective studies and data analysis are needed to determine the appropriate candidates and cancer types.
Article
Pharmacology & Pharmacy
Dianlong Jia, Feifei Wang, Yue Lu, Ping Hu, Rui Wang, Guangyong Li, Renmin Liu, Jun Li, Huimin Liu, Qing Fan, Fengjiao Yuan
Summary: In this study, EGFR-targeting TRAIL (Z-TRAIL) was successfully designed by genetically fusing an EGFR-antagonistic affibody (ZEGFR:1907) to TRAIL. Z-TRAIL showed enhanced cytotoxicity and apoptosis-inducing ability in EGFR-overexpressing tumors both in vitro and in vivo, and also exhibited antitumor efficacy against low-expressing EGFR tumors. Furthermore, Z-TRAIL did not show obvious acute toxicity in mice, suggesting its potential as a promising agent for targeted therapy of EGFR-expressing tumors.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Oncology
Benjamin Lin, Julia Ziebro, Erin Smithberger, Kasey R. Skinner, Eva Zhao, Timothy F. Cloughesy, Zev A. Binder, Donald M. O'Rourke, David A. Nathanson, Frank B. Furnari, C. Ryan Miller
Summary: This article discusses the unique biology of EGFR in GBM, the challenges in treatment, and how they have influenced past and present EGFR-targeted therapeutic design and clinical trials. It also explores the adjustments needed to exploit EGFR in this disease.
Article
Biochemistry & Molecular Biology
Zahra Motamedi, Hassan Rajabi-Maham, Maryam Azimzadeh Irani
Summary: The ErbB family of receptor tyrosine kinases play essential roles in cell differentiation and proliferation, with mutation or overexpression leading to various cancers. Among the four homologous members, glycosylated EGFR-ErbB2 heterodimer was found to be more stable compared to the EGFR-EGFR homodimer, indicating glycosylation promotes heterodimer formation as the dominant mechanism for receptor activation.
JOURNAL OF MOLECULAR MODELING
(2021)
