A promising therapeutic strategy for metastatic gestational trophoblastic disease: Engineered anticancer gene‑expressing stem cells to selectively target choriocarcinoma (Review)

Abstract

Gestational trophoblastic disease (GTD) is an unusual disease occurring in pregnancy that originates from abnormal trophoblastic cells and comprises a group of diseases with different properties of invasion, metastasis and recurrence. The GTD group includes hydatidiform moles and gestational trophoblastic neoplasms (GTNs), with GTNs being divided into invasive moles, choriocarcinoma, placental site trophoblastic tumors and epithelioid trophoblastic tumors. The present review focuses on current effective treatments for GTD, including conventional and novel promising direct enzyme prodrug therapies (DEPTs). Conventional therapies, such as chemotherapy and hysterectomy, are currently used in a clinical setting; however, the use of diverse DEPTs, including antibody-DEPT and gene-DEPT is also being attempted to cure GTNs. In addition, gene delivery tools using genetically engineered neural stem cells (NSCs) are presently being examined for the treatment of GTNs. The tumor-tropism of NSCs by chemoattractant factors is a unique characteristic of these cells and can serve as a vehicle to deliver anticancer agents. Previous studies have demonstrated that injection with NSC-expressing suicide genes into xenograft animal models has a significant inhibitory effect on tumor growth. Stem cells can be genetically engineered to express anticancer genes, which migrate to the metastatic sites and selectively target cancer cells, and are considered to effectively target metastatic GTNs. However, the safety issue of stem cell therapy, such as tumorigenesis, remains a challenge. Novel therapies comprising a combination of conventional and novel promising treatments are anticipated to be definitive treatments for metastasized and/or recurrent patients with GTNs.

Trophoblastic Disease: Review of the Literature

“…Ši išvisa gali metastazuoti į kitus organus, pavyzdžiui, į makštį, vulvą, plaučius. Dažniausi invazyvios pūslinės išvisos klinikiniai požymiai: gimdos padidėjimas ir kraujavimas iš gimdos, kai nenustatoma kitų galimų priežasčių [4].…”

“…Choriokarcinoma -retas onkologinis susirgimas, linkęs metastazuoti į kitus organus hematogeniškai. Pagrindinis simptomas -ūminis kraujavimas iš makšties [4].…”

“…Epitelioidiniai trofoblastiniai navikai (ETN) -gana reta patologija, būdingesnė moterims, kurioms jau buvo nustatyta pūslinė išvisa ar patyrusioms savaiminių persileidimų. Šie navikai auga lėtai ir yra itin atsparūs chemoterapijai [4].…”

“…Atlikti keli klinikiniai tyrimai atskleidė, kad profilaktinės chemoterapijos taikymas smarkiai sumažino pasikartojančios ar gydymui atsparios gestacinės trofoblastinės ligos atsiradimo riziką. Minėtinas G. S. Kimo ir bendraautorių [4] atliktas tyrimas. Tyrimo metu 262 pacientės, kurioms diagnozuota didelės rizikos pūslinė išvisa, suskirstytos į dvi tiriamųjų grupes: pirmosios grupės pacientėms (n = 50) taikyta profilaktinė vieno vaisto chemoterapija, likusios pacientės sudarė antrąją, t. y. kontrolinę, grupę.…”

Doxorubicin resistant choriocarcinoma cell line derived spheroidal cells exhibit stem cell markers but reduced invasion

“…In fact, choriocarcinoma is a malignant tumour of the uterus which originates in the foetal chorion. It is characterized by abnormal proliferation of trophoblast without the formation of chorionic villi (Greaves and Maley 2012 ; Kim et al 2019 ). This gestational cancer is chemotherapy-sensitive but metastatic (Braga et al 2019 ).…”