Perspectives on the Treatment of Advanced Thyroid Cancer: Approved Therapies, Resistance Mechanisms, and Future Directions

Porter, Ashleigh; Wong, Deborah Jean Lee

doi:10.3389/fonc.2020.592202

Cited by 38 publications

(42 citation statements)

References 33 publications

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“…Additionally, while the majority of DTCs can be cured with surgery followed by hormone replacement and radioactive iodine (RAI, also called I-131) [ 6 ], the management of advanced, poorly differentiated, and anaplastic TCs is far more challenging [ 19 , 20 , 21 ]. These tumors can be treated with tyrosine kinase inhibitors (TKIs) [ 22 ], such as lenvatinib and sorafenib for DTC, dabrafenib, trametinib, and vemurafenib for BRAF mutated PTC or ATC, cabozantinib and vandetanib for MTC, or selpercaptinib in RET mutated MTCs [ 10 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Opportunities and Challenges of Liquid Biopsy in Thyroid Cancer

Romano

Martorana

Pennisi

et al. 2021

IJMS

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Thyroid cancer is the most common malignancy of the endocrine system, encompassing different entities with distinct histological features and clinical behavior. The diagnostic definition, therapeutic approach, and follow-up of thyroid cancers display some controversial aspects that represent unmet medical needs. Liquid biopsy is a non-invasive approach that detects and analyzes biological samples released from the tumor into the bloodstream. With the use of different technologies, tumor cells, free nucleic acids, and extracellular vesicles can be retrieved in the serum of cancer patients and valuable molecular information can be obtained. Recently, a growing body of evidence is accumulating concerning the use of liquid biopsy in thyroid cancer, as it can be exploited to define a patient’s diagnosis, estimate their prognosis, and monitor tumor recurrence or treatment response. Indeed, liquid biopsy can be a valuable tool to overcome the limits of conventional management of thyroid malignancies. In this review, we summarize currently available data about liquid biopsy in differentiated, poorly differentiated/anaplastic, and medullary thyroid cancer, focusing on circulating tumor cells, circulating free nucleic acids, and extracellular vesicles.

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Section: Introductionmentioning

confidence: 99%

Opportunities and Challenges of Liquid Biopsy in Thyroid Cancer

Romano

Martorana

Pennisi

et al. 2021

IJMS

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“…Another feature that contributes to the exceptionality of this case is the patient's 9-year PFS, far superior to the PFS reported in most studies with vandetanib or other TKIs in metastatic MTC [5,14]. In addition, the complete disappearance of the breast metastatic lesions is truly unusual.…”

Section: Discussionmentioning

confidence: 60%

“…Selpercatinib and pralsetinib were the first RET inhibitors approved. They have shown promising results in terms of overall response rate in patients with RET-mutated MTC, even those whose tumors had progressed on TKI treatment [5].…”

Section: Introductionmentioning

confidence: 99%

An Unusual Case of Hypopituitarism as an Adverse Effect of Vandetanib and Remission of Breast Metastases in a Patient with Medullary Thyroid Cancer

et al. 2021

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Introduction: Tyrosine kinase inhibitors have been a breakthrough in the treatment of advanced medullary thyroid cancer (MTC), and they can prolong progression-free survival (PFS). Case Presentation: A patient with MTC and metastatic spread to the lymph nodes, lungs, bones, breast, and cerebellum started treatment with vandetanib. During treatment, she developed secondary adrenal insufficiency and hypogonadotropic hypogonadism. After 9 years of vandetanib therapy, the disease has not progressed and the patient maintains a complete response of the breast metastases and a partial response of the other metastatic lesions. Conclusion: To our knowledge, this is the first reported case of secondary adrenal insufficiency and hypogonadotropic hypogonadism related to therapy with vandetanib. Moreover, the prolonged PFS and the complete disappearance of some of the metastatic lesions in this patient are truly unusual.

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“…Conversely, this approach is not effective in the radioiodine refractory DTC and especially in ATC. For these extremely aggressive malignancies, promising effects are being obtained by the use of novel therapeutic approaches [ 5 , 6 , 33 ], but, in many cases, the resistance to the current treatments is still a fundamental unresolved issue.…”

Section: Discussionmentioning

confidence: 99%

“…The current management of ATC has strongly been conditioned by the advent of the molecular testing of thyroid tumors which permits to target the known genetic mutations [ 4 ] with the new molecular drugs, mainly inhibitors of tyrosine kinases [ 5 , 6 ]. However, for the tumors resistant to these new drugs and those without known detectable genetic aberrations, the current treatment is still represented by palliative surgery and systemic chemotherapy, the latter consisting in taxane monotherapy or combined with carboplatin or anthracyclines [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Dihydrotanshinone I on Proliferation and Invasiveness of Paclitaxel-Resistant Anaplastic Thyroid Cancer Cells

Allegri

Capriglione

Maggisano

et al. 2021

IJMS

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ATC is a very rare, but extremely aggressive form of thyroid malignancy, responsible for the highest mortality rate registered for thyroid cancer. In patients without known genetic aberrations, the current treatment is still represented by palliative surgery and systemic mono- or combined chemotherapy, which is often not fully effective for the appearance of drug resistance. Comprehension of the mechanisms involved in the development of the resistance is therefore an urgent issue to suggest novel therapeutic approaches for this very aggressive malignancy. In this study, we created a model of anaplastic thyroid cancer (ATC) cells resistant to paclitaxel and investigated the characteristics of these cells by analyzing the profile of gene expression and comparing it with that of paclitaxel-sensitive original ATC cell lines. In addition, we evaluated the effects of Dihydrotanshinone I (DHT) on the viability and invasiveness of paclitaxel-resistant cells. ATC paclitaxel-resistant cells highlighted an overexpression of ABCB1 and a hyper-activation of the NF-κB compared to sensitive cells. DHT treatment resulted in a reduction of viability and clonogenic ability of resistant cells. Moreover, DHT induces a decrement of NF-κB activity in SW1736-PTX and 8505C-PTX cells. In conclusion, to the best of our knowledge, the results of the present study are the first to demonstrate the antitumor effects of DHT on ATC cells resistant to Paclitaxel in vitro.

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Perspectives on the Treatment of Advanced Thyroid Cancer: Approved Therapies, Resistance Mechanisms, and Future Directions

Cited by 38 publications

References 33 publications

Opportunities and Challenges of Liquid Biopsy in Thyroid Cancer

Opportunities and Challenges of Liquid Biopsy in Thyroid Cancer

An Unusual Case of Hypopituitarism as an Adverse Effect of Vandetanib and Remission of Breast Metastases in a Patient with Medullary Thyroid Cancer

Effects of Dihydrotanshinone I on Proliferation and Invasiveness of Paclitaxel-Resistant Anaplastic Thyroid Cancer Cells

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