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Impact of Age-Related Genetic Differences on the Therapeutic Outcome of Papillary Thyroid Cancer

 Seok-Mo Kim  ;  Soo Young Kim  ;  Cheong Soo Park  ;  Hang-Seok Chang  ;  Ki Cheong Park 
 CANCERS, Vol.12(2) : E448, 2020 
Journal Title
Issue Date
EMT ; FGFR ; Lenvatinib ; Sorafenib ; papillary thyroid carcinoma
The incidence of papillary thyroid carcinoma (PTC) has been increasing worldwide. PTC is the most common type of differentiated thyroid cancer and usually shows good prognosis. However, some PTC is driven to advanced stage by epithelial-mesenchymal transition (EMT)-mediated drug resistance, which is particularly noticeable in pediatric patients. There are limited options for systemic treatment, necessitating development of new clinical approaches. Here, we aimed to clarify genetic differences due to age of patients with PTC, and thereby aid in developing novel therapeutics. Patients with biochemically and histologically confirmed PTC were included in this study. PTC cells were acquired from young and older patients showing drug resistance, and were compared via microarray analysis. Cellular proliferation and other properties were determined after treatments with lenvatinib and sorafenib. In vivo, tumor volume and other properties were examined using a mouse xenograft model. Lenvatinib-treated group showed obvious suppression of markers of anti-apoptosis, EMT, and the FGFR signaling pathway, compared with control and Sorafenib-treated group. In the xenograft models, lenvatinib treatment induced significant tumor shrinkage and blocked the proto-oncogene Bcl-2 (B cell lymphoma/leukemia gene-2) and FGFR signaling pathway, along with reduced levels of EMT markers, compared with control and Sorafenib-treated group. Our findings clarify the age-dependent characteristics of pediatric PTC, giving insights into the relationship between young age and poor prognosis. Furthermore, it provides a basis for developing novel therapeutics tailored to the age at diagnosis.
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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Seok Mo(김석모) ORCID logo https://orcid.org/0000-0001-8070-0573
Kim, Soo Young(김수영) ORCID logo https://orcid.org/0000-0002-8919-3456
Park, Ki Cheong(박기청) ORCID logo https://orcid.org/0000-0002-3435-3985
Park, Cheong Soo(박정수)
Chang, Hang Seok(장항석) ORCID logo https://orcid.org/0000-0002-5162-103X
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