Version 1
: Received: 6 May 2022 / Approved: 9 May 2022 / Online: 9 May 2022 (14:06:20 CEST)
How to cite:
Padmanabhan, R.; Kheraldine, H.; Gupta, I.; Meskin, N.; Hamad, A.; Vranic, S.; Al Moustafa, A. Mathematical Modeling of the Growth Suppression of HER2+ Breast Cancer Colonies Under the Effect of Trastuzumab and PD-1/PD-L1 Inhibitor. Preprints2022, 2022050120. https://doi.org/10.20944/preprints202205.0120.v1
Padmanabhan, R.; Kheraldine, H.; Gupta, I.; Meskin, N.; Hamad, A.; Vranic, S.; Al Moustafa, A. Mathematical Modeling of the Growth Suppression of HER2+ Breast Cancer Colonies Under the Effect of Trastuzumab and PD-1/PD-L1 Inhibitor. Preprints 2022, 2022050120. https://doi.org/10.20944/preprints202205.0120.v1
Padmanabhan, R.; Kheraldine, H.; Gupta, I.; Meskin, N.; Hamad, A.; Vranic, S.; Al Moustafa, A. Mathematical Modeling of the Growth Suppression of HER2+ Breast Cancer Colonies Under the Effect of Trastuzumab and PD-1/PD-L1 Inhibitor. Preprints2022, 2022050120. https://doi.org/10.20944/preprints202205.0120.v1
APA Style
Padmanabhan, R., Kheraldine, H., Gupta, I., Meskin, N., Hamad, A., Vranic, S., & Al Moustafa, A. (2022). Mathematical Modeling of the Growth Suppression of HER2+ Breast Cancer Colonies Under the Effect of Trastuzumab and PD-1/PD-L1 Inhibitor. Preprints. https://doi.org/10.20944/preprints202205.0120.v1
Chicago/Turabian Style
Padmanabhan, R., Semir Vranic and Ala-Eddin Al Moustafa. 2022 "Mathematical Modeling of the Growth Suppression of HER2+ Breast Cancer Colonies Under the Effect of Trastuzumab and PD-1/PD-L1 Inhibitor" Preprints. https://doi.org/10.20944/preprints202205.0120.v1
Abstract
Immune checkpoint blockade (ICB)-based therapy is revolutionizing cancer treatment by fostering successful immune surveillance and effector cell responses against various types of cancers. However, patients with HER2+ cancers are yet to benefit from this therapeutic strategy. Precisely, several questions regarding the right combination of drugs, drug modality, and effective dose recommendations pertaining to the use of ICB-based therapy for HER2+ patients remain unanswered. In this study, we use a mathematical modeling-based approach to quantify the growth inhibition of HER2+ breast cancer (BC) cell colonies (ZR75) when treated with anti-HER2; trastuzumab (TZ) and anti-PD-1/PD-L1 (BMS-202) agents. Our data show that a combination therapy of TZ and BMS-202 can significantly reduce the viability of ZR75 cells and trigger several morphological changes. The combination decreased the cell’s invasiveness along with altering several key pathways, such as Akt/mTor and ErbB2 compared to monotherapy. In addition, BMS-202 causes dose-dependent growth inhibition of HER2+ BC cell colonies alone, while this effect is significantly improved when used in combination with TZ. Based on the in-vitro monoculture experiments conducted, we argue that BMS-202 can cause tumor growth suppression not only by mediating immune response but also by interfering with the growth signaling pathways of HER2+ BC. Nevertheless, further studies are imperative to substantiate this argument and to uncover the potential crosstalk between PD-1/PD-L1 inhibitors and HER2 growth signaling pathways in breast cancer.
Keywords
HER2; PD-1/PD-L1; Mathematical model; HER2/PD-1 Interaction; Breast cancer
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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