Effects of Anti-Cancer Drug Sensitivity-Related Genetic Differences on Therapeutic Approaches in Refractory Papillary Thyroid Cancer.

Hyeok Jun Yun,Ki Cheong Park,Hang-Seok Chang,Yonjung Kim,Sungsoon Fang,Minki Kim,Sang Yong Kim,Ho-Jin Chang

doi:10.3390/ijms23020699

Abstract

Thyroid cancer (TC) includes tumors of follicular cells; it ranges from well differentiated TC (WDTC) with generally favorable prognosis to clinically aggressive poorly differentiated TC (PDTC) and undifferentiated TC (UTC). Papillary thyroid cancer (PTC) is a WDTC and the most common type of thyroid cancer that comprises almost 70–80% of all TC. PTC can present as a solid, cystic, or uneven mass that originates from normal thyroid tissue. Prognosis of PTC is excellent, with an overall 10-year survival rate >90%. However, more than 30% of patients with PTC advance to recurrence or metastasis despite anti-cancer therapy; consequently, systemic therapy is limited, which necessitates expansion of improved clinical approaches. We strived to elucidate genetic distinctions due to patient-derived anti-cancer drug-sensitive or -resistant PTC, which can support in progress novel therapies. Patients with histologically proven PTC were evaluated. PTC cells were gained from drug-sensitive and -resistant patients and were compared using mRNA-Seq. We aimed to assess the in vitro and in vivo synergistic anti-cancer effects of a novel combination therapy in patient-derived refractory PTC. This combination therapy acts synergistically to promote tumor suppression compared with either agent alone. Therefore, genetically altered combination therapy might be a novel therapeutic approach for refractory PTC.

Highlights

Thyroid cancer (TC) accounts for more than 90% of endocrine cancer, which is the most common endocrine malignancy, and its onset rate has risen over the past four decades [1]
Recent research trends have proven that progress of epithelial–mesenchymal transition (EMT) in refractory cancer cells results in metastasis but is a critical causing factor in drug resistance via fibroblast growth factor receptor (FGFR) signaling [18,19]
57 medical records of patients with advanced or metastatic papillary TC (PTC) consecutively treated with paclitaxel (n = 5), lenvatinib (n = 36), or sorafenib (n = 16) at our center were analyzed

Summary

Introduction

Thyroid cancer (TC) accounts for more than 90% of endocrine cancer, which is the most common endocrine malignancy, and its onset rate has risen over the past four decades [1]. Though a few previous researchers have suggested molecular dissimilarities to describe the aggressive conduct of PTC in drugresistant patients, no investigation has yet offered an explicit account of the underlying mechanism. Even though EMT is a crucial factor in resistance to ErbB aiming composites, deficient perception of the molecular process elementary course has restrained the advance of clinical approaches aimed at drug-resistance condition [22,23]. A few investigations have established that the FGFR signaling pathway plays a decisive role in EMT mediated poor prognosis and drug-resistance of refractory cancer [24,25,26,27] by its alteration of the aggressiveness or cancer stemness of refractory tumor cells

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