TY - JOUR
T1 - Repositioning of Anti-Inflammatory Drugs for the Treatment of Cervical Cancer Sub-Types
AU - Kori, Medi
AU - Arga, Kazim Yalcin
AU - Mardinoglu, Adil
AU - Turanli, Beste
N1 - Funding Information:
This work was supported by TUBITAK through project number 119S999, and funded by Knut and Alice Wallenberg Foundation.
Publisher Copyright:
Copyright © 2022 Kori, Arga, Mardinoglu and Turanli.
PY - 2022/6/13
Y1 - 2022/6/13
N2 - Cervical cancer is the fourth most commonly diagnosed cancer worldwide and, in almost all cases is caused by infection with highly oncogenic Human Papillomaviruses (HPVs). On the other hand, inflammation is one of the hallmarks of cancer research. Here, we focused on inflammatory proteins that classify cervical cancer patients by considering individual differences between cancer patients in contrast to conventional treatments. We repurposed anti-inflammatory drugs for therapy of HPV-16 and HPV-18 infected groups, separately. In this study, we employed systems biology approaches to unveil the diagnostic and treatment options from a precision medicine perspective by delineating differential inflammation-associated biomarkers associated with carcinogenesis for both subtypes. We performed a meta-analysis of cervical cancer-associated transcriptomic datasets considering subtype differences of samples and identified the differentially expressed genes (DEGs). Using gene signature reversal on HPV-16 and HPV-18, we performed both signature- and network-based drug reversal to identify anti-inflammatory drug candidates against inflammation-associated nodes. The anti-inflammatory drug candidates were evaluated using molecular docking to determine the potential of physical interactions between the anti-inflammatory drug and inflammation-associated nodes as drug targets. We proposed 4 novels anti-inflammatory drugs (AS-601245, betamethasone, narciclasin, and methylprednisolone) for the treatment of HPV-16, 3 novel drugs for the treatment of HPV-18 (daphnetin, phenylbutazone, and tiaprofenoic acid), and 5 novel drugs (aldosterone, BMS-345541, etodolac, hydrocortisone, and prednisolone) for the treatment of both subtypes. We proposed anti-inflammatory drug candidates that have the potential to be therapeutic agents for the prevention and/or treatment of cervical cancer.
AB - Cervical cancer is the fourth most commonly diagnosed cancer worldwide and, in almost all cases is caused by infection with highly oncogenic Human Papillomaviruses (HPVs). On the other hand, inflammation is one of the hallmarks of cancer research. Here, we focused on inflammatory proteins that classify cervical cancer patients by considering individual differences between cancer patients in contrast to conventional treatments. We repurposed anti-inflammatory drugs for therapy of HPV-16 and HPV-18 infected groups, separately. In this study, we employed systems biology approaches to unveil the diagnostic and treatment options from a precision medicine perspective by delineating differential inflammation-associated biomarkers associated with carcinogenesis for both subtypes. We performed a meta-analysis of cervical cancer-associated transcriptomic datasets considering subtype differences of samples and identified the differentially expressed genes (DEGs). Using gene signature reversal on HPV-16 and HPV-18, we performed both signature- and network-based drug reversal to identify anti-inflammatory drug candidates against inflammation-associated nodes. The anti-inflammatory drug candidates were evaluated using molecular docking to determine the potential of physical interactions between the anti-inflammatory drug and inflammation-associated nodes as drug targets. We proposed 4 novels anti-inflammatory drugs (AS-601245, betamethasone, narciclasin, and methylprednisolone) for the treatment of HPV-16, 3 novel drugs for the treatment of HPV-18 (daphnetin, phenylbutazone, and tiaprofenoic acid), and 5 novel drugs (aldosterone, BMS-345541, etodolac, hydrocortisone, and prednisolone) for the treatment of both subtypes. We proposed anti-inflammatory drug candidates that have the potential to be therapeutic agents for the prevention and/or treatment of cervical cancer.
KW - anti-inflammatory drugs
KW - cervical cancer
KW - drug repurposing
KW - human papillomavirus 16
KW - human papillomavirus 18
KW - inflammation
UR - http://www.scopus.com/inward/record.url?scp=85133461878&partnerID=8YFLogxK
U2 - 10.3389/fphar.2022.884548
DO - 10.3389/fphar.2022.884548
M3 - Article
AN - SCOPUS:85133461878
SN - 1663-9812
VL - 13
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - 884548
ER -
