Effects and Role of Multikinase Inhibitors in Thyroid Cancer

Laursen, Rasmus; Wehland, Markus; Kopp, Sascha; Pietsch, Jessica; Infanger, Manfred; Grosse, Jirka; Grimm, Daniela

doi:10.2174/1381612822666160614084943

Cited by 40 publications

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“…It decreases angiogenesis and lymphogenesis, stunts tumor growth and damages the tumor’s microenvironment [11,22]. VEGFR (vascular endothelial growth factor receptor), PDGFR (platelet derived growth factor receptor), FGFR (fibroblast growth factor receptor), RET (rearranged during transfection), RAS (rat sarcoma), PI3K (phosphatidylinositol-3-kinase), AKT (protein kinase B), mTOR (mammalian target of rapamycin), RAF (rapidly accelerated fibrosarcoma kinase), MAPKK (mitogen activated protein kinase kinase), ERK (extracellular signal regulated kinase).…”

Section: Figurementioning

confidence: 99%

“…Regrettably, about 20% of patients experience recurrence of the disease. The recurrent form of thyroid cancer is poorly differentiated and thereby more malignant; this makes it for example resistant to RAI ablation because due to an inability to take up iodine [11]. …”

Section: Introductionmentioning

confidence: 99%

“…Sunitinib (Sunitinib malate; Sutent; Pfizer, New York, USA) is a multi-targeted TKI used in the treatment of metastatic renal cell carcinomas (RCC) and gastrointestinal stromal tumors, and is under evaluation for other malignancies [11]. It inhibits VEGFR-1 and -2, platelet-derived growth factor receptors, stem cell factor receptor (c-KIT), FLT3 as well as RET kinases.…”

Section: Introductionmentioning

confidence: 99%

“…Sunitinib acts on VEGF receptors and on RET and is therefore a suitable drug to treat RAI-refractory thyroid cancer. Sunitinib is still not approved for thyroid cancer therapy by the FDA, and therefore therapy approaches applying sunitinib are still off-label [11]. …”

Section: Introductionmentioning

confidence: 99%

“…The agent has an anti-proliferative effect and an anti-angiogenic activity by blocking the intracellular signal transduction of VEGFR2 in endothelial cells [11]. Sorafenib is a FDA-approved drug for patients with RAI-refractory metastatic thyroid cancer.…”

Section: Introductionmentioning

confidence: 99%

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The Adverse Effect of Hypertension in the Treatment of Thyroid Cancer with Multi-Kinase Inhibitors

Ancker

Wehland

Bauer

et al. 2017

IJMS

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Abstract:The treatment of thyroid cancer has promising prospects, mostly through the use of surgical or radioactive iodine therapy. However, some thyroid cancers, such as progressive radioactive iodine-refractory differentiated thyroid carcinoma, are not remediable with conventional types of treatment. In these cases, a treatment regimen with multi-kinase inhibitors is advisable. Unfortunately, clinical trials have shown a large number of patients, treated with multi-kinase inhibitors, being adversely affected by hypertension. This means that treatment of thyroid cancer with multi-kinase inhibitors prolongs progression-free and overall survival of patients, but a large number of patients experience hypertension as an adverse effect of the treatment. Whether the prolonged lifetime is sufficient to develop sequelae from hypertension is unclear, but late-stage cancer patients often have additional diseases, which can be complicated by the presence of hypertension. Since the exact mechanisms of the rise of hypertension in these patients are still unknown, the only available strategy is treating the symptoms. More studies determining the pathogenesis of hypertension as a side effect to cancer treatment as well as outcomes of dose management of cancer drugs are necessary to improve future therapy options for hypertension as an adverse effect to cancer therapy with multi-kinase inhibitors.

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Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Adverse Effect of Hypertension in the Treatment of Thyroid Cancer with Multi-Kinase Inhibitors

Ancker

Wehland

Bauer

et al. 2017

IJMS

Self Cite

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Predictors of recurrence after total thyroidectomy plus neck dissection and radioactive iodine ablation for high‐risk papillary thyroid carcinoma

Kim

Roh

Song

et al. 2020

Journal of Surgical Oncology

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Background American Thyroid Association (ATA) proposed management guidelines for differentiated thyroid cancer, including a three‐tiered risk stratification system for structural recurrence. This study aimed to compare the various 2015 ATA criteria for the strength of association with the recurrence of high‐risk papillary thyroid carcinoma (PTC). Study Design This study included 545 consecutive patients who underwent total thyroidectomy plus neck dissection and radioactive iodine ablation (RAI) for previously untreated high‐risk PTC. The association of recurrence‐free survival (RFS) with clinicopathological factors was evaluated by univariate and multivariate Cox proportional hazard regression analyses. Results During a follow‐up median period of 89 months, 90 (16.5%) patients had any‐site recurrence. Of the high‐risk factors, high stimulated thyroglobulin (sTg) level and >3‐cm sized lymph nodes (LNs) were significantly associated with recurrence (all P < .005). Sex, tumor size, lymphovascular invasion, multifocality, number of positive LNs, extranodal extension, T and N classifications, and overall tumor‐node‐metastasis stage were also significantly associated with recurrence (all P < .05). In multivariate analyses, high sTg level [adjusted hazard ratio (HR) = 7.18] and N1b (adjusted HR = 3.27) were independent factors predictive of recurrence (all P ≤ .001). Conclusions Postoperative high serum sTg level might be the most important predictor of PTC recurrence after total thyroidectomy plus neck dissection and RAI.

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Novel therapeutic clues in thyroid carcinomas: The role of targeting cancer stem cells

Antonelli

Motta

2017

Medicinal Research Reviews

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Thyroid carcinomas (TCs), the most common endocrine tumors, represent the eighth most common cancer diagnosed worldwide in both women and men. To treat these malignancies, several drugs are now available and a number of novel ones have been enrolling in clinical trials, addressing both oncogenic pathways in cancer cells and angiogenic pathways in tumor endothelial cells. However, their use is not devoid of serious toxicities and their efficacy is limited, being dependent on carcinoma typology and the occurrence of acquired resistance. Accordingly, it is time to recast therapeutic strategies against these types of tumors to get to newer and fully effective drugs. In this perspective, latest findings demonstrate that cancer stem cells (CSCs) represent a challenging target to strike. They possess core traits of self-renewal and differentiation, being resistant to the effects of chemotherapy and radiation and playing a key role in mediating metastasis. Therefore, basic molecular elements sustaining both development of thyroid cancer stem cells and their residence in the stemness condition represent a set of innovative and still unexplored targets to address. In this review, a thorough literature survey has been accomplished, to take stock of mechanisms governing thyroid carcinomas and to point out both their currently available treatments and the novel forthcoming ones. Pubmed, Scifinder and ClinicalTrials.gov were exploited as research applications and registry database, respectively. Original articles, reviews, and editorials published within the last ten years, as well as open clinical investigations in the field, were analyzed to suggest new exciting therapeutic opportunities for people affected by TCs.

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Effects and Role of Multikinase Inhibitors in Thyroid Cancer

Abstract: The frequently adverse effects seen in TKI treatment require further investigation. A well-adjusted balance between efficacy and adverse effects is desirable. No effects on overall survival were reported. Therefore, further studies are required.

Cited by 40 publications

References 0 publications

The Adverse Effect of Hypertension in the Treatment of Thyroid Cancer with Multi-Kinase Inhibitors

The Adverse Effect of Hypertension in the Treatment of Thyroid Cancer with Multi-Kinase Inhibitors

Predictors of recurrence after total thyroidectomy plus neck dissection and radioactive iodine ablation for high‐risk papillary thyroid carcinoma

Novel therapeutic clues in thyroid carcinomas: The role of targeting cancer stem cells

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