Patient-derived tumoroids of high-grade neuroendocrine neoplasms for more personalised therapies

12 Mar 2024
Patient-derived tumoroids of high-grade neuroendocrine neoplasms for more personalised therapies

A recent study published in npj Precision Oncology suggests that a precision oncology approach using PD tumoroids could provide personalised therapeutic options for patients with advanced high-grade gastroenteropancreatic neuroendocrine neoplasms.

In the context of rare cancers like high-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN), there are significant challenges in discovering and validating therapeutic targets due to the lack of predictive biomarkers and representative preclinical models. Therapy selection for these cancers relies heavily on clinical experience rather than large clinical trials.

To address this, researchers established patient-derived tumoroids (PD tumoroids) from stored tissue samples of advanced high-grade GEP-NEN patients. Using these tumoroids, they conducted rapid ex vivo testing of drugs, genetic sequencing, and profiling of responses to treatment. These tumoroids accurately mirrored patient responses to standard chemotherapies, suggesting their utility in personalised treatment selection.

The study compared the drug responses of tumoroids outside the body to the responses of patients undergoing chemotherapy. By doing so, the researchers were able to identify stress responses induced by the treatment. This analysis helped in identifying potential synergies between certain drugs and led to the discovery of new therapeutic targets.

The study highlighted the scarcity of preclinical disease models for rare cancers and emphasized the importance of patient-derived models like PD tumoroids for studying such conditions. These tumoroids retained key biological features of high-grade GEP-NEN and reflected inter-patient molecular patterns, demonstrating their relevance in mimicking the disease. Despite the small sample size, the study's results aligned with findings from similar-sized studies in other cancer types, indicating the clinical applicability of patient-derived models.

The research introduced an efficient workflow for processing low-abundant GEP-NEN tissues, ensuring rapid turnaround times for ex vivo drug testing. This approach facilitates personalised screening of treatment efficacy, particularly crucial for patients with aggressive cancers who require prompt intervention. Moreover, the study identified potential therapeutic targets, including Lysine Demethylase 5 A (KDM5A) and interferon-beta 1 (IFNB1), which showed synergistic effects with cisplatin in combination therapy. Further validation in larger cohorts is needed to confirm the efficacy and specificity of these combinations, along with understanding their underlying mechanisms.

Overall, the study's findings contribute to advancing personalised clinical protocols for later-line therapies in patients with high-grade GEP-NEN, offering new avenues for treatment selection and combination strategies.

Source: npj Precision Oncology