Human-Derived Model Systems in Gynecological Cancer Research

Abstract

The human female reproductive tract (FRT) is a complex system that combines series of organs, including ovaries, fallopian tubes, uterus, cervix, vagina, and vulva; each of which possesses unique cellular characteristics and functions. This versatility, in turn, allows for the development of a wide range of epithelial gynecological cancers with distinct features. Thus, reliable model systems are required to better understand the diverse mechanisms involved in the regional pathogenesis of the reproductive tract and improve treatment strategies. Here, we review the current human-derived model systems available to study the multitude of gynecological cancers, including ovarian, endometrial, cervical, vaginal, and vulvar cancer, and the recent advances in the push towards personalized therapy.

Application of Ovarian Cancer Organoids in Precision Medicine: Key Challenges and Current Opportunities

“…Although PDXs show remarkable preservation for histological characteristics and molecular heterogeneity of original tumor in previous OC research ( Aparicio et al, 2015 ), the genomic stability over multiple generations has also been recently questioned by a study that reported accumulated genetic changes of copy number alterations over passages ( Ben-David et al, 2017 ). Additionally, because of the slow speed of tumor growth, low engraftment rates, and high costs, the PDX platform application is limited for high-throughput screening and large-scale clinical applications ( Lohmussaar et al, 2020a ). Moreover, PDXs based on immunocompromised mice are limited in experiments of immunomodulatory compounds ( Chen and Mellman, 2017 ).…”

“…OC organoids can closely recapitulate primary tissue in terms of structures and functions, as promising mini-replicas of cancer tissues ( Maru et al, 2019a ). Moreover, OC organoids can maintain a genomic landscape and tumor heterogeneity of original cells to a large extent, thus serving as an amazing in vitro tool to discover the underlying mechanism of cancer processes in preclinical research ( Lohmussaar et al, 2020a ). Despite these strengths, OC organoids also have several limitations.…”

Patient-derived organoids and high grade serous ovarian cancer: from disease modeling to personalized medicine

“…In this scenario, an emerging technology that holds promise of significantly impacting the clinical management of patients in the near future is represented by patient-derived Organoids (PDOs). Indeed, elegant studies carried out in the past 2-3 years have clearly indicated that HGSOC PDOs have the potential to faithfully reproduce many of the challenging characteristics of the tumor from which they derive in a reasonable time frame and at sustainable costs [6][7][8][9][10]. This technology may offer the possibility of attaining truly personalized drug-based therapy.…”

Organoids and epithelial ovarian cancer ‑ a future tool for personalized treatment decisions?

“…Patients' tumor biopsies are dissociated into fragments and cells, embedded in a 3D extracellular matrix scaffold (such as Matrigel) and cultured in a cocktail of growth and signaling factors, which must be defined and optimized for each cancer type (26). Organoids have evolved through the last decade and now closely reflect primary tissue's biology and pathology, enabling their use in a broad range of applications, such as drug development and drug screening (22,(27)(28)(29).…”

“…Multiple organoids may be generated from different tumor areas to mimic tumor heterogeneity (30,31). Of note, tumor organoids capture inter-and intratumor heterogeneity (29). The establishment of tumor-derived organoids from various cancer types such as colon, pancreatic, gastric, prostate, breast, esophageal, bladder and endometrial cancers has been reported (30)(31)(32)(33)(34)(35)(36)(37).…”