Human blood serum can donor-specifically antagonize effects of EGFR-targeted drugs on squamous carcinoma cell growth
Dmitry Kamashev,
Maksim Sorokin,
Irina Kochergina,
Aleksey Drobyshev,
Uliana Vladimirova,
Marianna Zolotovskaia,
Igor Vorotnikov,
Nina Shaban,
Mikhail Raevskiy,
Denis Kuzmin,
Anton Buzdin
Affiliations
Dmitry Kamashev
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; Corresponding author.
Maksim Sorokin
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; Moscow Institute of Physics and Technology (National Research University), Moscow Region 141700, Russia
Irina Kochergina
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10, Miklukho-Maklaya St., Moscow 117997, Russia
Aleksey Drobyshev
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; Moscow Institute of Physics and Technology (National Research University), Moscow Region 141700, Russia
Uliana Vladimirova
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
Marianna Zolotovskaia
Moscow Institute of Physics and Technology (National Research University), Moscow Region 141700, Russia
Igor Vorotnikov
Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia
Nina Shaban
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10, Miklukho-Maklaya St., Moscow 117997, Russia; Moscow Institute of Physics and Technology (National Research University), Moscow Region 141700, Russia
Mikhail Raevskiy
Moscow Institute of Physics and Technology (National Research University), Moscow Region 141700, Russia; OmicsWay Corp., Walnut, CA, USA
Denis Kuzmin
Moscow Institute of Physics and Technology (National Research University), Moscow Region 141700, Russia
Anton Buzdin
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; Moscow Institute of Physics and Technology (National Research University), Moscow Region 141700, Russia
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 EGFR 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.
