Discovery of Promising Inhibitors of Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), Estrogen Receptor (ER), and Phosphatidylinositol-3-kinase a (PI3Ka) for Personalized Breast Cancer Treatment
Despite the rapid developments and advancements to improve treatments, Breast cancer remains one of the deadliest health challenges and the most frequently diagnosed tumor. One of the major problems with treatment is the unique difference that each cancerous cell exhibits. As a result, treatment of...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2022-10-01
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| Series: | Cancer Informatics |
| Online Access: | https://doi.org/10.1177/11769351221127862 |
| _version_ | 1811199211389059072 |
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| author | Precious A Akinnusi Samuel O Olubode Ayomide O Adebesin Toluwani A Nana Sidiqat A Shodehinde |
| author_facet | Precious A Akinnusi Samuel O Olubode Ayomide O Adebesin Toluwani A Nana Sidiqat A Shodehinde |
| author_sort | Precious A Akinnusi |
| collection | DOAJ |
| description | Despite the rapid developments and advancements to improve treatments, Breast cancer remains one of the deadliest health challenges and the most frequently diagnosed tumor. One of the major problems with treatment is the unique difference that each cancerous cell exhibits. As a result, treatment of breast cancer has now become more personalized based on the specific features of the tumor such as overexpression of growth factor receptors (Epidermal growth factor receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2)), hormone receptors (Human Estrogen receptor alpha (ER)) and kinases involved in pivotal signaling associated with growth (Phosphatidylinositol 3-kinase (PI3K)). Several chemotherapeutic agents have been developed to curb the menace, but the associated adverse drug effects cannot be overlooked. To this end, this study employed a molecular modeling approach to identify novel compounds of natural origin that can potentially antagonize the receptors (mentioned above) associated with the pathophysiology of breast cancer and at the same time pose very little or no side effects. The results of the molecular model of biological interactions between a library of 118 anthocyanins and the binding pockets of the protein targets identified 5 compounds (Pelargonin, Delphinidin 3- O -rutinoside, Malvin, Cyanidin-3-(6-acetylglucoside), and Peonidin 3- O -rutinoside) with good binding affinities to the protein targets. Further MM-GBSA calculations returned high binding energies. The specific molecular interactions between the compounds and the targets were analyzed and reported herein. Also, all the compounds exhibited good pharmacokinetic profiles and are therefore recommended for further analyses as they could be explored as new treatment options for a broad range and personalized breast cancer treatments. |
| first_indexed | 2024-04-12T01:44:13Z |
| format | Article |
| id | doaj.art-96e44cec336640cab24a973a506fb456 |
| institution | Directory Open Access Journal |
| issn | 1176-9351 |
| language | English |
| last_indexed | 2024-04-12T01:44:13Z |
| publishDate | 2022-10-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cancer Informatics |
| spelling | doaj.art-96e44cec336640cab24a973a506fb4562022-12-22T03:53:07ZengSAGE PublishingCancer Informatics1176-93512022-10-012110.1177/11769351221127862Discovery of Promising Inhibitors of Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), Estrogen Receptor (ER), and Phosphatidylinositol-3-kinase a (PI3Ka) for Personalized Breast Cancer TreatmentPrecious A Akinnusi0Samuel O Olubode1Ayomide O Adebesin2Toluwani A Nana3Sidiqat A Shodehinde4Department of Biochemistry, Adekunle Ajasin University, Akungba-Akoko, NigeriaDepartment of Biochemistry, Adekunle Ajasin University, Akungba-Akoko, NigeriaDepartment of Biochemistry, Cancer Genomics Lab, Covenant University, Ota, NigeriaDepartment of Biochemistry, Covenant University, NigeriaDepartment of Biochemistry, Adekunle Ajasin University, Akungba-Akoko, NigeriaDespite the rapid developments and advancements to improve treatments, Breast cancer remains one of the deadliest health challenges and the most frequently diagnosed tumor. One of the major problems with treatment is the unique difference that each cancerous cell exhibits. As a result, treatment of breast cancer has now become more personalized based on the specific features of the tumor such as overexpression of growth factor receptors (Epidermal growth factor receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2)), hormone receptors (Human Estrogen receptor alpha (ER)) and kinases involved in pivotal signaling associated with growth (Phosphatidylinositol 3-kinase (PI3K)). Several chemotherapeutic agents have been developed to curb the menace, but the associated adverse drug effects cannot be overlooked. To this end, this study employed a molecular modeling approach to identify novel compounds of natural origin that can potentially antagonize the receptors (mentioned above) associated with the pathophysiology of breast cancer and at the same time pose very little or no side effects. The results of the molecular model of biological interactions between a library of 118 anthocyanins and the binding pockets of the protein targets identified 5 compounds (Pelargonin, Delphinidin 3- O -rutinoside, Malvin, Cyanidin-3-(6-acetylglucoside), and Peonidin 3- O -rutinoside) with good binding affinities to the protein targets. Further MM-GBSA calculations returned high binding energies. The specific molecular interactions between the compounds and the targets were analyzed and reported herein. Also, all the compounds exhibited good pharmacokinetic profiles and are therefore recommended for further analyses as they could be explored as new treatment options for a broad range and personalized breast cancer treatments.https://doi.org/10.1177/11769351221127862 |
| spellingShingle | Precious A Akinnusi Samuel O Olubode Ayomide O Adebesin Toluwani A Nana Sidiqat A Shodehinde Discovery of Promising Inhibitors of Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), Estrogen Receptor (ER), and Phosphatidylinositol-3-kinase a (PI3Ka) for Personalized Breast Cancer Treatment Cancer Informatics |
| title | Discovery of Promising Inhibitors of Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), Estrogen Receptor (ER), and Phosphatidylinositol-3-kinase a (PI3Ka) for Personalized Breast Cancer Treatment |
| title_full | Discovery of Promising Inhibitors of Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), Estrogen Receptor (ER), and Phosphatidylinositol-3-kinase a (PI3Ka) for Personalized Breast Cancer Treatment |
| title_fullStr | Discovery of Promising Inhibitors of Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), Estrogen Receptor (ER), and Phosphatidylinositol-3-kinase a (PI3Ka) for Personalized Breast Cancer Treatment |
| title_full_unstemmed | Discovery of Promising Inhibitors of Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), Estrogen Receptor (ER), and Phosphatidylinositol-3-kinase a (PI3Ka) for Personalized Breast Cancer Treatment |
| title_short | Discovery of Promising Inhibitors of Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), Estrogen Receptor (ER), and Phosphatidylinositol-3-kinase a (PI3Ka) for Personalized Breast Cancer Treatment |
| title_sort | discovery of promising inhibitors of epidermal growth factor receptor egfr human epidermal growth factor receptor 2 her2 estrogen receptor er and phosphatidylinositol 3 kinase a pi3ka for personalized breast cancer treatment |
| url | https://doi.org/10.1177/11769351221127862 |
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