RESUMEN
Ovarian cancer (OC) is a major cause of gynecological cancer mortality, necessitating enhanced research. Organoids, cellular clusters grown in 3D model, have emerged as a disruptive paradigm, transcending the limitations inherent to conventional models by faithfully recapitulating key morphological, histological, and genetic attributes. This review undertakes a comprehensive exploration of the potential in organoids derived from murine, healthy population, and patient origins, encompassing a spectrum that spans foundational principles to pioneering applications. Organoids serve as preclinical models, allowing us to predict how patients will respond to treatments and guiding the development of personalized therapies. In the context of evaluating new drugs, organoids act as versatile platforms, enabling thorough testing of innovative combinations and novel agents. Remarkably, organoids mimic the dynamic nature of OC progression, from its initial formation to the spread to other parts of the body, shedding light on intricate details that hold significant importance. By functioning at an individualized level, organoids uncover the complex mechanisms behind drug resistance, revealing strategic opportunities for effective treatments.
Asunto(s)
Ginecología , Neoplasias Ováricas , Humanos , Femenino , Animales , Ratones , Medicina de Precisión , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Organoides/patologíaRESUMEN
Endometrial cancer (EC) is the most common female reproductive tract cancer and its incidence has been continuously increasing in recent years. The underlying mechanisms of EC tumorigenesis remain unclear, and efficient target therapies are lacking, for both of which feasible endometrial cancer animal models are essential but currently limited. Here, an organoid and genome editing-based strategy to generate primary, orthotopic, and driver-defined ECs in mice is reported. These models faithfully recapitulate the molecular and pathohistological characteristics of human diseases. The authors names these models and similar models for other cancers as organoid-initiated precision cancer models (OPCMs). Importantly, this approach can conveniently introduce any driver mutation or a combination of driver mutations. Using these models,it is shown that the mutations in Pik3ca and Pik3r1 cooperate with Pten loss to promote endometrial adenocarcinoma in mice. In contrast, the Kras G12D mutati led to endometrial squamous cell carcinoma. Then, tumor organoids are derived from these mouse EC models and performed high-throughput drug screening and validation. The results reveal distinct vulnerabilities of ECs with different mutations. Taken together, this study develops a multiplexing approach to model EC in mice and demonstrates its value for understanding the pathology of and exploring the potential treatments for this malignancy.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Endometriales , Femenino , Animales , Ratones , Humanos , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Mutación/genética , Modelos AnimalesRESUMEN
Fluorescence-guided surgery has emerged as a promising imaging technique for real-time intraoperative tumour delineation and visualisation of submillimetre tumour masses in cytoreductive surgery for epithelial ovarian cancer (EOC). Researchers have developed several EOC-targeted fluorescent probes, most of which are currently in the preclinical stage. Interestingly, imaging devices designed for open surgery are proof of concept. This review summarises the recent advances in EOC-targeted fluorescent probes and open-field fluorescence imaging strategies and discusses the challenges and potential solutions for clinical translation.