Sunitinib in the Treatment of Thyroid Cancer

Ferrari, Silvia; Centanni, Marco; Virili, Camilla; Miccoli, Mario; Ferrari, Paola; Ruffilli, Ilaria; Ragusa, Francesca; Antonelli, Alessandro; Fallahi, Poupak

doi:10.2174/0929867324666171006165942

Cited by 70 publications

(55 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sunitinib is a tyrosine kinase inhibitor commonly used to treat stromal tumors, renal carcinoma, and pancreatic neuroendocrine tumors [377]. Sunitinib-induced cardiotoxic effects have been reported in patients including hypertension, left ventricular systolic dysfunction, and congestive heart failure [378,379].…”

Section: Sunitinibmentioning

confidence: 99%

CYP1B1 as a therapeutic target in cardio-oncology

2020

View full text Add to dashboard Cite

Cardiovascular complications have been frequently reported in cancer patients and survivors, mainly because of various cardiotoxic cancer treatments. Despite the known cardiovascular toxic effects of these treatments, they are still clinically used because of their effectiveness as anti-cancer agents. In this review, we discuss the growing body of evidence suggesting that inhibition of the cytochrome P450 1B1 enzyme (CYP1B1) can be a promising therapeutic strategy that has the potential to prevent cancer treatment-induced cardiovascular complications without reducing their anti-cancer effects. CYP1B1 is an extrahepatic enzyme that is expressed in cardiovascular tissues and overexpressed in different types of cancers. A growing body of evidence is demonstrating a detrimental role of CYP1B1 in both cardiovascular diseases and cancer, via perturbed metabolism of endogenous compounds, production of carcinogenic metabolites, DNA adduct formation, and generation of reactive oxygen species (ROS). Several chemotherapeutic agents have been shown to induce CYP1B1 in cardiovascular and cancer cells, possibly via activating the Aryl hydrocarbon Receptor (AhR), ROS generation, and inflammatory cytokines. Induction of CYP1B1 is detrimental in many ways. First, it can induce or exacerbate cancer treatment-induced cardiovascular complications. Second, it may lead to significant chemo/radio-resistance, undermining both the safety and effectiveness of cancer treatments. Therefore, numerous preclinical studies demonstrate that inhibition of CYP1B1 protects against chemotherapy-induced cardiotoxicity and prevents chemo- and radio-resistance. Most of these studies have utilized phytochemicals to inhibit CYP1B1. Since phytochemicals have multiple targets, future studies are needed to discern the specific contribution of CYP1B1 to the cardioprotective and chemo/radio-sensitizing effects of these phytochemicals.

show abstract

Section: Sunitinibmentioning

confidence: 99%

CYP1B1 as a therapeutic target in cardio-oncology

2020

View full text Add to dashboard Cite

show abstract

“…In humans, several multikinase inhibitors have been utilized for the treatment of advanced-stage thyroid tumours. [25][26][27][28][29][30][31][32] In veterinary medicine, the multikinase inhibitor toceranib phosphate 1 was approved by the Food and Drug Administration (FDA) after it was demonstrated to have biologic activity in the treatment of canine, recurrent or nonresectable, grade 2 or 3 mast cell tumours (MCTs). [33][34][35][36] Additionally, responses were observed for a spectrum of solid tumour histotypes in a phase 1 study.…”

mentioning

confidence: 99%

Toceranib phosphate in the treatment of canine thyroid carcinoma: 42 cases (2009‐2018)

Sheppard‐Olivares

Bello

Wood

et al. 2020

Vet Comparative Oncology

View full text Add to dashboard Cite

Thyroid carcinoma is the most common endocrine malignancy in dogs. Thyroidectomy and radiation therapy control local disease, yet are not always feasible, and efficacious medical therapies need to be identified. Toceranib phosphate has been reported to provide clinical benefit (CB) in dogs with thyroid carcinoma, while its role in treatment-naïve thyroid tumours has not been well-described. The objective of this study was to describe the use of toceranib in the management of thyroid carcinomas in dogs in both the naïve-disease and prior therapy-settings. A medical record search identified 42 dogs diagnosed with thyroid carcinoma and treated with toceranib, of which 26 and 16 dogs were in settings of naïve-disease and after prior therapy, respectively. Twenty-three (88.4%) and twelve (75%) dogs experienced CB in the naïve and prior therapy settings, respectively. The median [95% confidence interval] progression free interval (PFI) for dogs in the naïve and prior therapy settings were 206 [106,740] and 1015 [92,1015] days, respectively. The median overall survival time (OST) for dogs in the naïve and prior therapy settings were 563 [246,916] and 1082 [289,1894] days, respectively. Overall, the data provided no evidence for differences in overall PFI (P > .20) or OST (P = .15) between settings. However, when asymptomatic at the time of diagnosis, dogs in the naïve setting showed poorer survival prognosis (estimated hazard ratio 17.2 [1.8, 163]) relative to dogs in the prior therapy setting. This study characterizes PFI, OST and CB with minimal AE in dogs with thyroid carcinoma treated with toceranib in both the naïve and prior therapy settings.

show abstract

“…The mechanisms of action of Sunitinib ( Figure 1A) is an MKI currently approved for the treatment of gastrointestinal stromal tumors, renal carcinoma, and pancreatic neuroendocrine tumors. It blocks the signals from VEGFR-1, -2, -3, the platelet-derived growth factor receptor (PDGFR), the stem cell factor receptor (c-KIT), FMS-like tyrosine kinase 3 (FLT-3), and RET [19][20][21].…”

Section: Int J Mol Sci 2019 20 X For Peer Review 3 Of 20mentioning

confidence: 99%

Multikinase Inhibitor Treatment in Thyroid Cancer

Ancker

Krüger

Wehland

et al. 2019

IJMS

View full text Add to dashboard Cite

Thyroid cancer is the most common endocrine malignancy. Most thyroid cancer types respond well to conventional treatment consisting of surgery and radioactive iodine (RAI) therapy. Unfortunately, some thyroid cancer types are resistant to surgical and RAI therapy. Multikinase inhibitors (MKIs) can be used in the treatment of advanced refractory thyroid cancers. The objective of this review is to give an update on MKI treatment (lenvatinib, sorafenib, sunitinib, cabozantinib, pazopanib, vandetanib) of thyroid cancer, regarding its efficacy and safety profile. We evaluated 212 articles through a PubMed search. A total of 20 articles met the inclusion and none the exclusion criteria. The studies showed promising progression-free survival rates compared to placebo treatment from earlier studies and similar or better results compared to the SELECT and DECISION trials. Adverse effects (AEs) are substantial in the treatment with MKIs. Almost all patients treated with these novel drugs experienced AEs. It is therefore crucial to focus on the management of AEs for a decent long-term outcome. The AEs are often more severe in patients with high efficacy of MKIs, which could indicate a correlation. Taken together, the novel therapeutic regimen with MKIs has shown favorable results in otherwise treatment-resistant thyroid cancer.

show abstract

Sunitinib in the Treatment of Thyroid Cancer

Abstract: Even if sunitinib is promising in the therapy of differentiated thyroid carcinoma (DTC), until now no phase III studies have been published, and additional prospective researches are necessary in order to evaluate the real efficacy of sunitinib in aggressive thyroid cancer.

Cited by 70 publications

References 71 publications

CYP1B1 as a therapeutic target in cardio-oncology

CYP1B1 as a therapeutic target in cardio-oncology

Toceranib phosphate in the treatment of canine thyroid carcinoma: 42 cases (2009‐2018)

Multikinase Inhibitor Treatment in Thyroid Cancer

Contact Info

Product

Resources

About