Resistance of papillary thyroid cancer stem cells to chemotherapy

Abstract

Abstract. Thyroid carcinoma is the most common endocrine neoplasm, with the highest mortality rate of all the endocrine cancers. Among the endocrine malignancies, ~80% are papillary thyroid carcinomas (PTCs). In the initiation and progression of this tumor, genetic alterations in the mitogen-associated protein kinase pathway, including RAS point mutations, RET/PTC oncogene rearrangements and BRAF point mutations, play an important role, particularly in deciding targeted therapy. In the present study, a small population of thyroid tumor cells, known as tumor spheres, were isolated and characterized from PTC surgical samples. These spheres can be expanded indefinitely in vitro and give rise to differentiated adherent cells when cultivated in differentiative conditions. The present study showed by reverse transcription-polymerase chain reaction and flow cytometric analysis that the undifferentiated PTC cells exhibited a characteristic antigen expression profile of adult progenitor/stem cells. The cells were more resistant to chemotherapeutics, including bortezomib, taxol, cisplatin, etoposide, doxorubicin and vincristine, than differentiated PTC cells and the majority possessed a quiescent status, as revealed by the various cell cycle characteristics and anti-apoptotic protein expression. Such advances in cancer thyroid stem cell biology may provide relevant information for future targeted therapies.

Allicin activates autophagic cell death to alleviate the malignant development of thyroid cancer

“…The incidence of thyroid cancer is continuing to increase worldwide (20). Compared with males, females of various ethnicities demonstrate a higher incidence of thyroid cancer (21,22).…”

“…Unfortunately, it is common for these patients to develop drug resistance (23,24). Most thyroid cancer patients who develop incurable metastasis are candidates for neoadjuvant or palliative chemotherapy (20,25). However, two thirds of these patients still benefit from conventional chemotherapy.…”

“…Certain studies suggest that the pro-survival functions of autophagy decrease the efficacy of cancer therapeutics (20,25). However, other studies have demonstrated that autophagy also induced cancer cell death after various treatments (9,(28)(29)(30).…”

Retracted: LINC00311 promotes cancer stem‐like properties by targeting miR‐330‐5p/TLR4 pathway in human papillary thyroid cancer

“…Further in clinical studies, stem cell markers have been found upregulated in PTC tissues, and the expression levels of these markers were positively correlated with lymph node, tumors metastasis stage . For treatment, one study suggested that PTC was more resistant to bortezomib, taxol, cisplatin, etoposide, and other chemotherapeutics drugs . In addition, another study reported that the expression of CD15, CD44, CD166, and ALDH1 was positively independently correlated with a shorter progression‐free survival (PFS) .…”

Cancer stem cells as a potential therapeutic target in thyroid carcinoma

“…of cancer therapy (27). Therefore, increased understanding of the characteristics of thyroid CSCs and the identification of therapeutic agents that target the CSC population may lead to the development of novel treatments that specifically target ATC and advanced forms of differentiated tumors.…”