Quantification of the growth suppression of HER2+ breast cancer colonies under the effect of trastuzumab and PD-1/PD-L1 inhibitor
IntroductionImmune 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,...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-12-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.977664/full |
| _version_ | 1797978483578634240 |
|---|---|
| author | Regina Padmanabhan Hadeel Kheraldine Hadeel Kheraldine Ishita Gupta Ishita Gupta Nader Meskin Anas Hamad Semir Vranic Ala-Eddin Al Moustafa Ala-Eddin Al Moustafa |
| author_facet | Regina Padmanabhan Hadeel Kheraldine Hadeel Kheraldine Ishita Gupta Ishita Gupta Nader Meskin Anas Hamad Semir Vranic Ala-Eddin Al Moustafa Ala-Eddin Al Moustafa |
| author_sort | Regina Padmanabhan |
| collection | DOAJ |
| description | IntroductionImmune 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.MethodsIn 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.Results and discussionOur 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. |
| first_indexed | 2024-04-11T05:23:40Z |
| format | Article |
| id | doaj.art-4257b04f8488484fa9be0dcaadc87c62 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T05:23:40Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-4257b04f8488484fa9be0dcaadc87c622022-12-23T10:50:07ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-12-011210.3389/fonc.2022.977664977664Quantification of the growth suppression of HER2+ breast cancer colonies under the effect of trastuzumab and PD-1/PD-L1 inhibitorRegina Padmanabhan0Hadeel Kheraldine1Hadeel Kheraldine2Ishita Gupta3Ishita Gupta4Nader Meskin5Anas Hamad6Semir Vranic7Ala-Eddin Al Moustafa8Ala-Eddin Al Moustafa9Department of Electrical Engineering, Qatar University, Doha, QatarCollege of Medicine, Qatar University (QU) Health, Qatar University, Doha, QatarBiomedical Research Centre, Qatar University, Doha, QatarCollege of Medicine, Qatar University (QU) Health, Qatar University, Doha, QatarBiomedical Research Centre, Qatar University, Doha, QatarDepartment of Electrical Engineering, Qatar University, Doha, QatarPharmaceutical Department at Hamad Medical Corporation, Hamad Medical Corporation, Doha, QatarCollege of Medicine, Qatar University (QU) Health, Qatar University, Doha, QatarCollege of Medicine, Qatar University (QU) Health, Qatar University, Doha, QatarBiomedical Research Centre, Qatar University, Doha, QatarIntroductionImmune 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.MethodsIn 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.Results and discussionOur 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.https://www.frontiersin.org/articles/10.3389/fonc.2022.977664/fullHER2PD-1/PD-L1mathematical modelHER2/PD-1 interactionbreast cancer |
| spellingShingle | Regina Padmanabhan Hadeel Kheraldine Hadeel Kheraldine Ishita Gupta Ishita Gupta Nader Meskin Anas Hamad Semir Vranic Ala-Eddin Al Moustafa Ala-Eddin Al Moustafa Quantification of the growth suppression of HER2+ breast cancer colonies under the effect of trastuzumab and PD-1/PD-L1 inhibitor Frontiers in Oncology HER2 PD-1/PD-L1 mathematical model HER2/PD-1 interaction breast cancer |
| title | Quantification of the growth suppression of HER2+ breast cancer colonies under the effect of trastuzumab and PD-1/PD-L1 inhibitor |
| title_full | Quantification of the growth suppression of HER2+ breast cancer colonies under the effect of trastuzumab and PD-1/PD-L1 inhibitor |
| title_fullStr | Quantification of the growth suppression of HER2+ breast cancer colonies under the effect of trastuzumab and PD-1/PD-L1 inhibitor |
| title_full_unstemmed | Quantification of the growth suppression of HER2+ breast cancer colonies under the effect of trastuzumab and PD-1/PD-L1 inhibitor |
| title_short | Quantification of the growth suppression of HER2+ breast cancer colonies under the effect of trastuzumab and PD-1/PD-L1 inhibitor |
| title_sort | quantification of the growth suppression of her2 breast cancer colonies under the effect of trastuzumab and pd 1 pd l1 inhibitor |
| topic | HER2 PD-1/PD-L1 mathematical model HER2/PD-1 interaction breast cancer |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.977664/full |
| work_keys_str_mv | AT reginapadmanabhan quantificationofthegrowthsuppressionofher2breastcancercoloniesundertheeffectoftrastuzumabandpd1pdl1inhibitor AT hadeelkheraldine quantificationofthegrowthsuppressionofher2breastcancercoloniesundertheeffectoftrastuzumabandpd1pdl1inhibitor AT hadeelkheraldine quantificationofthegrowthsuppressionofher2breastcancercoloniesundertheeffectoftrastuzumabandpd1pdl1inhibitor AT ishitagupta quantificationofthegrowthsuppressionofher2breastcancercoloniesundertheeffectoftrastuzumabandpd1pdl1inhibitor AT ishitagupta quantificationofthegrowthsuppressionofher2breastcancercoloniesundertheeffectoftrastuzumabandpd1pdl1inhibitor AT nadermeskin quantificationofthegrowthsuppressionofher2breastcancercoloniesundertheeffectoftrastuzumabandpd1pdl1inhibitor AT anashamad quantificationofthegrowthsuppressionofher2breastcancercoloniesundertheeffectoftrastuzumabandpd1pdl1inhibitor AT semirvranic quantificationofthegrowthsuppressionofher2breastcancercoloniesundertheeffectoftrastuzumabandpd1pdl1inhibitor AT alaeddinalmoustafa quantificationofthegrowthsuppressionofher2breastcancercoloniesundertheeffectoftrastuzumabandpd1pdl1inhibitor AT alaeddinalmoustafa quantificationofthegrowthsuppressionofher2breastcancercoloniesundertheeffectoftrastuzumabandpd1pdl1inhibitor |