Targeted therapies for advanced thyroid cancer

Puxeddu, Efisio; Romagnoli, Serena; Dottorini, Massimo E.

doi:10.1097/cco.0b013e328340cf94

Cited by 22 publications

(15 citation statements)

References 52 publications

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“…A multistep model has been proposed as a mechanism for the neoplastic process in thyroid cancer, involving the main genetic mutations that provoke the tumor-initiating process in a follicular cell, and the phenomenon of oncogenic addiction to these particular mutations that makes them particularly interesting for directed therapy (Puxeddu et al 2011). One of the most important activating genetic mutations involves the RET/PTC-RAS-RAF-MAPK axis.…”

Section: Introductionmentioning

confidence: 99%

Sorafenib in metastatic thyroid cancer

Capdevila¹,

Iglesias²,

Halperín³

et al. 2012

Endocrine-Related Cancer

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Although thyroid cancer usually has an excellent prognosis, few therapeutic options are available in the refractory setting. Based on the recent results of phase II studies with tyrosine kinase inhibitors, we designed a retrospective analysis of patients with metastatic thyroid cancer treated with sorafenib in seven Spanish referral centers. Consecutive patients with progressive metastatic thyroid cancer (papillary, follicular, medullary, and anaplastic) not suitable for curative surgery, radioactive-iodine therapy, or radiotherapy were treated with sorafenib 400 mg twice a day. The primary end point was objective response rate (RR). Secondary end points included toxicity, median progression-free survival (mPFS), median overall survival (mOS), and correlation between tumor marker levels (thyroglobulin, calcitonin, and carcinoembryonic antigen) and efficacy. Between June 2006 and January 2010, 34 patients were included in the study. Sixteen patients presented differentiated thyroid carcinomas (DTC) of which seven (21%) were papillary, nine (26%) follicular, 15 (44%) medullary (MTC), and three (9%) were anaplastic (ATC). Eleven (32%) patients achieved partial response and 14 (41%) had stable disease beyond 6 months. Regarding histological subtype, RRs were 47% (seven of 15) for MTC, 19% (three of 16) for DTC, and 33% (one of three) for ATC. With a median follow-up of 11.5 months, mPFS were 13.5, 10.5, and 4.4 months for DTC, MTC, and ATC respectively. Tumor markers were evaluated in 22 patients, and a statistically significant association was observed between RR and decrease in tumor marker levels O50% (PZ0.033). In this retrospective trial, sorafenib showed antitumor efficacy in all histological subtypes of thyroid cancer, warranting further development in this setting.

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Section: Introductionmentioning

confidence: 99%

Sorafenib in metastatic thyroid cancer

Capdevila¹,

Iglesias²,

Halperín³

et al. 2012

Endocrine-Related Cancer

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“…Several small molecular inhibitors have been developed, and a few have already reached the stage of clinical trials [18]. In detail, sorafenib, a multikinase inhibitor, which targets also RAF family of kinases, has recently been tested in a phase III trial.…”

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confidence: 99%

BRAF mutation assessment in papillary thyroid cancer: are we ready to use it in clinical practice?

Puxeddu

2013

Endocrine

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“…Furthermore, the overall safety profile was acceptable and adverse events were consistent with other sorafenib trials (19). In light of these promising results, a phase III study evaluating the efficacy and safety of sorafenib in advanced/metastatic iodine refractory thyroid cancer was initiated (18). Additionally, some guidelines have begun to recommend sorafenib in patients with iodine-refractory progressive metastatic disease who are not willing or able to enter previous clinical trials.…”

Section: Squamousmentioning

confidence: 99%

“…Three phase II studies have been conducted to determine the efficacy of sorafenib in advanced follicular thyroid cancer (18). These studies showed that sorafenib had significant activity with partial responses ranging from 15-25% and stabilization of the disease occurring in an additional 34-56% of the patients.…”

Section: Squamousmentioning

confidence: 99%

Molecular targeted therapies for cancer: Sorafenib monoï¿½therapy and its combination with other therapies (Review)

Ibrahim

Walsh

et al. 2012

Oncol Rep

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Abstract. Sorafenib is an oral multikinase inhibitor that acts by inhibiting tumor growth and disrupting tumor microvasculature through antiproliferative, anti-angiogenic and proapoptotic effects. It exerts these effects via inhibition of multiple targets including Raf serine/threonine kinases, vascular endothelial growth factor receptor tyrosine kinases; VEGFR-1, VEGFR-2, VEGFR-3 and platelet-derived growth factor receptor β (PDGFR-β). Current literature shows that the deregulated signaling through these receptors is commonly seen in human tumors. In addition, sorafenib is also shown to induce apoptosis through downregulation of Mcl-1 in many cancer types. Hence, sorafenib as a single agent has shown promising activity in some cancers such as renal cell carcinoma (RCC), hepatocellular carcinoma (HCC) and thyroid cancers. Currently, the drug holds FDA approval for the treatment of advanced RCC and unresectable HCC. However, many clinical studies have indicated several limitations to the application of sorafenib as a single agent in various other cancers. Owing to these reasons and the potential of sorafenib to synergize with other anticancer therapies, its combination with other targeted agents and chemotherapy has been widely explored with promising results. In addition, it has also shown synergistic results when combined with radiation. This review summarizes the current basic and clinical studies on the effects and mechanisms of sorafenib either administered alone or in combination with other anticancer treatments. IntroductionSince the 1980s, the field of cancer treatment has experienced a major paradigm shift from broad-spectrum cytotoxic chemotherapeutics to the development of targeted therapies tailored to inhibit cancer-specific pathways (1). This change was prompted by the limitations of the treatment mainstays in those days, which were surgery, chemotherapy and radiotherapy. Surgery was limited to early non-metastatic diseases, however, research demonstrates that solid tumors are frequently metastatic at presentation (2). Radiation and chemotherapy has limited capacity to discriminate between cancerous and normal cells and hence, results in severe side effects (3). Furthermore, solid tumors are inherently resistant to both radiation and chemotherapy. Therefore, the rationale for development of molecular targeted therapies was to overcome drug resistance, to make malignant cells more susceptible to suppression and damage whilst avoiding substantial toxicity to the rest of the body tissues and also to provide a higher therapeutic index.The molecular targeted therapies include monoclonal antibodies, tyrosine kinase inhibitors, rapamycin pathway inhibitors, proteasome inhibitors and inhibitors of Raf kinase (4). Many of these drugs have shown therapeutic benefit in various cancers, however, several challenges are yet to be conquered by the developers. These include overcoming certain amount of acquired resistance in cancer cells, selecting suitable dosage schedules, determining the stage to start treatmen...

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Targeted therapies for advanced thyroid cancer

Cited by 22 publications

References 52 publications

Sorafenib in metastatic thyroid cancer

Sorafenib in metastatic thyroid cancer

BRAF mutation assessment in papillary thyroid cancer: are we ready to use it in clinical practice?

Molecular targeted therapies for cancer: Sorafenib monoï¿½therapy and its combination with other therapies (Review)

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