Onco-PDO test utilizing patient-derived organoids (PDOs) and next-generation precision oncology in breast cancer.
Authors: Dantes Zahra , Huang Linda , Slawska Jolanta , Manjunath Apoorva , Zormaier Sandra , Ferreira Luciana , Steininger Anja , Mandlmeier Florian , Steiger Katja , Pfarr Nicole , Kiechle Marion , Rosell Rafael , Dantes Maurice , Lindner Kathrin , Weichert Wilko , Peschel Christian , Paepke Stefan 
Published: June 2023

e13594 Background: Facilitating personalized medicine and applying precision oncology in treating breast cancer (BC) requires in vitro model systems that mimic the disease's heterogeneity and the clinical response to cancer treatment. The capability of patient-derived organoids (PDOs) to serve as a paramount model in this regard has been shown. Nonetheless, offering this model in a clinically relevant timeframe to support clinical decisions persists challenging. Methods: To examine the feasibility of PDOs as a precision oncology platform to guide treatment decisions in the clinic, we are conducting a prospective exploratory study to establish PDOs from core needle biopsies and surgical samples and evaluate Onco-PDO drug testing in a short timeframe (10-14 days) after biopsy. In addition, PDOs are further expanded and characterized histologically, genomically, and biobanked. More importantly, the clinical response of patients is monitored and correlated with the PDO drug response. Results: To date, 85 tumor samples from the primary tumor (n=64) and lymph node metastases (n=21) were received from 73 patients recruited in our ongoing prospective exploratory study in the Invitrocue Munich laboratory. The median age stands at 51 years (range 28-85). The success rate of PDO generation holds at 90%. Up to now, the Onco-PDO test has been successfully performed in 75% of cases (n=64) and failed in 25% (n=21). A broad spectrum of standard-of-care chemotherapeutic and targeted drugs in BC were tested, resulting in 942 readouts. The heatmap of drug screening indicates the highest sensitivity to anthracyclines such as epirubicin (E) and doxorubicin (D) as a single agent or in combination with cyclophosphamide (EC and DC). In other drugs a higher variability in the range of drug sensitivity has been observed: i.e., paclitaxel (T; 0-98%), carboplatin (C; 0-99%), and the combination (TC; 0-99%), as well as 5-FU (0-100%) and vinorelbine (0-95%). Thus far, the analysis of clinical correlation could be performed in patients who received epirubicin resulting in a significant difference (p=0.03) in the IC-50 of epirubicin between responder and non-responder patients. Conclusions: The prospective exploratory study using Onco-PDO test by Invitrocue could overcome the previous challenges concerning the implementation of PDOs in clinical practice by standardizing the methodology for PDO generation especially from small starting material such as core needle biopsies and drug testing more rapidly and efficiently, leading to providing results within a clinically relevant timeframe of 14 days after obtaining a biopsy. The onco-PDO test might serve as an ideal test enabling precision oncology by identifying effective treatments and sparing unnecessary side effects from ineffective treatments.