Targeting Epidermal Growth Factor Receptor in Non-Small-Cell-Lung Cancer: Current State and Future Perspective

Author(s): Shui-Ming Bao, Qing-Hui Hu, Wen-Ting Yang, Yao Wang, Yin-Ping Tong, Wen-Dai Bao*.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 19 , Issue 8 , 2019

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Abstract:

Background: Lung cancer is one of the leading cause of cancer death worldwide, the most common histological type of lung cancer is non-small cell lung cancer (NSCLC), whose occurrence and development is closely related to the mutation and amplification of epidermal growth factor receptors (EGFR). Currently , a series of targeted drugs were developed on the inhibition of EGFR such as epidermal growth factor receptortyrosine kinase inhibitor EGFR-TKI and monoclonal antibody (McAb).

Objective: We sought to summarizes the current drugs targeting Epidermal Growth Factor Receptor in nonsmall- cell-lung.

Methods: We conducted a comprehensive review of the development and application of EGFR-TKI and McAb which targeted EGFR in NSCLC and compared the mechanisms of PROTAC with the traditional inhibitors.

Results: The drugs targeted EGFR in NSCLC have been widely used in clinic practices. Compared to traditional chemotherapy, these drugs excel with their clear and specific targeting, better curative effects, and less toxic and side effects. However, the mechanism comes with some insurmountable weaknesses like serious toxic and other side effects, as well as proneness to producing drug resistance.

Conclusion: The emerging PROTAC (Proteolysis Targeting Chimera) technology has been successfully applied to selective degradation of multiple protein targets, including EGFR. It also highlights the potential and challenges of PROTAC therapy regarding future combination therapeutic options in NSCLC treatment.

Keywords: NSCLC, protein inhibition, protein degradation, McAb, EGFR-TKls, PROTAC.

[1]
Semreen, M.H.; El-Gamal, M.I.; Ullah, S.; Jalil, S.; Zaib, S.; Anbar, H.S.; Lecka, J.; Sévigny, J.; Iqbal, J. Synthesis, biological evaluation, and molecular docking study of sulfonate derivatives as nucleotide pyrophosphatase/phosphodiesterase (NPP) inhibitors. Bioorg. Med. Chem., 2019, 27(13), 2741-2752.
[2]
Abdel-Maksoud, M.S.; El-Gamal, M.I.; Benhalilou, D.R.; Ashraf, S.; Mohammed, S.A.; Oh, C-H. Mechanistic/mammalian target of rapamycin: Recent pathological aspects and inhibitors. Med. Res. Rev., 2019, 39(2), 631-664.
[3]
Tarazi, H.; El-Gamal, M.I.; Oh, C-H. Discovery of highly potent V600E-B-RAF kinase inhibitors: Molecular modeling study. Bioorg. Med. Chem., 2019, 27(4), 655-663.
[4]
Abdel-Maksoud, M.S.; El-Gamal, M.I.; Gamal El-Din, M.M.; Oh, C.H. Design, synthesis, in vitro anticancer evaluation, kinase inhibitory effects, and pharmacokinetic profile of new 1,3,4-triarylpyrazole derivatives possessing terminal sulfonamide moiety. J. Enzyme Inhib. Med. Chem., 2019, 34(1), 97-109.
[5]
El-Gamal, M.I.; Park, B-J.; Oh, C-H. Synthesis, in vitro antiproliferative activity, and kinase inhibitory effects of pyrazole-containing diarylureas and diarylamides. Eur. J. Med. Chem., 2018, 156, 230-239.
[6]
El-Gamal, M.I.; Al-Ameen, S.K.; Al-Koumi, D.M.; Hamad, M.G.; Jalal, N.A.; Oh, C-H. Recent advances of colony-stimulating factor-1 receptor (CSF-1R) kinase and its inhibitors. J. Med. Chem., 2018, 61(13), 5450-5466.
[7]
Semreen, M.H.; El-Gamal, M.I.; Abdin, S.; Alkhazraji, H.; Kamal, L.; Hammad, S.; El-Awady, F.; Waleed, D.; Kourbaj, L. Recent updates of marine antimicrobial peptides. Saudi Pharm. J., 2018, 26(3), 396-409.
[8]
El-Gamal, M.I.; Oh, C-H. Pyrrolo [3,2-c]pyridine derivatives with potential inhibitory effect against FMS kinase: In vitro biological studies. J. Enzyme Inhib. Med. Chem., 2018, 33(1), 1160-1166.
[9]
Iqbal, J.; El-Gamal, M.I.; Ejaz, S.A.; Lecka, J.; Sévigny, J.; Oh, C-H. Tricyclic coumarin sulphonate derivatives with alkaline phosphatase inhibitory effects: In vitro and docking studies. J. Enzyme Inhib. Med. Chem., 2018, 33(1), 479-484.
[10]
Park, B-J.; El-Gamal, M.I.; Lee, W-S.; Shin, J-S.; Yoo, K.H.; Lee, K-T.; Oh, C-H. Synthesis and inhibitory effects of triarylpyrazoles on LPS-induced NO and PGE2 productions in RAW 264.7 macrophages. Med. Chem. Res., 2017, 26(9), 2161-2171.


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Article Details

VOLUME: 19
ISSUE: 8
Year: 2019
Page: [984 - 991]
Pages: 8
DOI: 10.2174/1871520619666190313161009
Price: $58

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