md-medicaldata

Authors

Rastko Prlić ¹, Mihailo Bezmarević ^1,2, Ivana Živić <sup>3

1</sup>Univerzitet odbrane, Medicinski fakultet Vojnomedicinske akademije, Beograd
²Klinika za opštu hirurgiju, Vojnomedicinska akademija, Beograd
³Ministarstvo odbrane Republike Srbije

 

UDK: 613.71/.74

The paper was received / Rad primljen 22.08.2025.

Accepted / Rad prihvaćen: 20.09.2025.

 

Correspondence to:

Rastko Prlić
Medicinski fakultet Vojnomedicinske akademije,
Beograd, Crnotravska 17
Tel:0643940003
e-mail: rastkoprlic@yahoo.co.uk

 

 

Sažetak

 

 

Medularni karcinom štitaste žlezde predstavlja neoplazmu koja potiče od parafolikularnih C- ćelija. Postoje dve forme medularnog karcinoma štitaste žlezde: nasledna i sporadična forma. Za nastanak nasledne forme medularnog karcinoma zaslužna je genetska mutacija na RET genu, a značajan procenat sporadičnih medularnih karcinoma u osnovi svoje patogeneze sadrži takođe mutacije RET gena. Postojanje velikog broja pacijenata sa uznapredovalim formama ovog karcinoma, gde je hirurški modalitet lečenja gotovo nemoguć, podstaklo je razvoj novih terapijskih linija. Upravo mutacija RET gena, poslužila je kao osnova za razvoj sistemske terapije. Nakon inicijalnog otkrića, potom proizvodnje multikinaznih inhibitora tirozin kinaza, danas su odobreni i u primeni kabozantinib i vandetanib. Česta nepodnošljivost terapije ovim lekovima i pojava rezistencije, dovela je do razvoja selektivnih inhibitora tirozin kinaze. Među selektivnim inhibitorima koriste se selperkatinib i pralsetinib, koji danas predstavljaju najnoviju formu terapije koja je pokazala izuzetne rezultate. Postojanje rezistencije i na selektivne inhibitore predstavlja najnoviji izazov u pronalaženju efikasnog farmakološkog agensa, kod pacijenata obolelih od medularnog karcinoma štitaste žlezde. Trenutno su u fazi istraživanja TPX-0046 i vepafestinib, kao i kombinacije selektivnih inhibitora sa određenim lekovima. Inovativna terapija medularnog karcinoma štitaste žlezde, koja je u proteklim godinama postala deo kliničke prakse u svetu, još uvek nije implementirana u zdravstvenom sistemu Republike Srbije. Cilj ovog rada jeste da prikaže dosadašnje pozitivne kliničke ishode i ukaže na terapijski potencijal ovog modaliteta lečenja, posebno za pacijente kod kojih su terapijske mogućnosti do sada bile ograničene na palijativni pristup, a iscrpljene su mogućnosti hirurškog lečenja. Trenutno je u Republici Srbiji od pomenutih TKI jedino registrovan kabozantinib i to za lečenje hepatocelularnog karcinoma (Hepatocellular Carcinoma - HCC) i karcinoma bubrežnih ćelija (Renal Cell Carcinoma – RCC).

 

Ključne reči:

medularni karcinom, rearranged in transfection (RET), sistemska terapija

 

 

 

Abstract

 

Medullary thyroid carcinoma is a neoplasm originating from parafollicular C cells. There are two forms of medullary thyroid carcinoma: hereditary and sporadic. The hereditary form of medullary carcinoma is caused by a gene mutation in the RET gene, and a significant percentage of sporadic medullary carcinomas also contains RET gene mutations in their pathogenesis. The existence of a large number of patients with advanced forms of this carcinoma, where surgical treatment is inadequate, has encouraged the development of new therapeutic lines. It is the RET gene mutation that served as the basis for the development of systemic therapy. First, multikinase tyrosine kinase inhibitors were developed, among which cabozantinib and vandetanib are currently approved. Frequent side effects associated with these drugs and the emergence of resistance led to the development of selective tyrosine kinase inhibitors. Among the selective inhibitors used, selpercatinib and pralsetinib are used as the latest form of therapy and have shown exceptional results. The onset of resistance to selective inhibitors represents the latest challenge in finding an effective pharmacological treatment modality in patients with medullary thyroid carcinoma. TPX-0046 and vepafestinib are currently under development , as well as combinations of selective inhibitors with certain drugs. The innovative therapy for medullary thyroid carcinoma, which in the past years has become part of clinical practice in the world, has not yet been implemented in the healthcare system of the Republic of Serbia. The aim of this review article is to show the positive clinical outcomes that have been documented recently and point out the therapeutic potential of this treatment modality, especially for patients whose therapeutic options have been limited to a palliative approach, when surgical treatment options have been exhausted. Currently, cabozantinib is the only registered TKI in the Republic of Serbia for the therapy of hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC).

 

Key words:

medullary carcinoma, rearranged in transfection (RET), systemic therapy

 

 

 

 

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