Kamashev Dmitry, Sorokin Maksim, Kochergina Irina, Drobyshev Aleksey, Vladimirova Uliana, Zolotovskaia Marianna, Vorotnikov Igor, Shaban Nina, Raevskiy Mikhail, Kuzmin Denis, Buzdin Anton
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10, Miklukho-Maklaya St., Moscow 117997, Russia.
World-Class Research Center "Digital Biodesign and Personalized Healthcare", Sechenov First Moscow State Medical University, 8-2, Trubetskaya St., Moscow 119992, Russia.
Heliyon. 2021 Mar 11;7(3):e06394. doi: 10.1016/j.heliyon.2021.e06394. eCollection 2021 Mar.
Many patients fail to respond to EGFR-targeted therapeutics, and personalized diagnostics is needed to identify putative responders. We investigated 1630 colorectal and lung squamous carcinomas and 1357 normal lung and colon samples and observed huge variation in EGFR pathway activation in both cancerous and healthy tissues, irrespectively on gene mutation status. We investigated whether human blood serum can affect squamous carcinoma cell growth and EGFR drug response. We demonstrate that human serum antagonizes the effects of EGFR-targeted drugs erlotinib and cetuximab on A431 squamous carcinoma cells by increasing IC50 by about 2- and 20-fold, respectively. The effects on clonogenicity varied significantly across the individual serum samples in every experiment, with up to 100% differences. EGF concentration could explain many effects of blood serum samples, and EGFR ligands-depleted serum showed lesser effect on drug sensitivity.
许多患者对表皮生长因子受体(EGFR)靶向治疗药物没有反应,因此需要个性化诊断来识别可能的反应者。我们研究了1630例结直肠癌和肺鳞癌以及1357例正常肺和结肠样本,观察到无论基因突变状态如何,癌组织和健康组织中EGFR通路激活都存在巨大差异。我们研究了人血清是否会影响肺鳞癌细胞的生长和EGFR药物反应。我们证明,人血清通过将半数抑制浓度(IC50)分别提高约2倍和20倍,拮抗EGFR靶向药物厄洛替尼和西妥昔单抗对A431肺鳞癌细胞的作用。在每个实验中,各个血清样本对克隆形成能力的影响差异显著,差异高达100%。表皮生长因子(EGF)浓度可以解释血清样本的许多作用,而不含EGFR配体的血清对药物敏感性的影响较小。