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

Int J Mol Sci. 2022 Jan 9;23(2):699. 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.

Keywords: EMT; FGFR; drug-resistant papillary thyroid cancer; lenvatinib; paclitaxel; patient-derived papillary thyroid cancer; sorafenib.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Drug Resistance, Neoplasm*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Paclitaxel / therapeutic use
  • Phenylurea Compounds / therapeutic use
  • Prognosis
  • Quinolines / therapeutic use
  • RNA-Seq
  • Sorafenib / therapeutic use
  • Thyroid Cancer, Papillary / drug therapy*
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / physiopathology
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Phenylurea Compounds
  • Quinolines
  • Sorafenib
  • lenvatinib
  • Paclitaxel