Pancreatic Ductal Adenocarcinoma (PDAC) Organoids: The Shining Light at the End of the Tunnel for Drug Response Prediction and Personalized Medicine

Abstract

Pancreatic ductal adenocarcinoma (PDAC) represents 90% of pancreatic malignancies. In contrast to many other tumor entities, the prognosis of PDAC has not significantly improved during the past thirty years. Patients are often diagnosed too late, leading to an overall five-year survival rate below 10%. More dramatically, PDAC cases are on the rise and it is expected to become the second leading cause of death by cancer in western countries by 2030. Currently, the use of gemcitabine/nab-paclitaxel or FOLFIRINOX remains the standard chemotherapy treatment but still with limited efficiency. There is an urgent need for the development of early diagnostic and therapeutic tools. To this point, in the past 5 years, organoid technology has emerged as a revolution in the field of PDAC personalized medicine. Here, we are reviewing and discussing the current technical and scientific knowledge on PDAC organoids, their future perspectives, and how they can represent a game change in the fight against PDAC by improving both diagnosis and treatment options.

The Anti-Dysenteric Drug Fraxetin Enhances Anti-Tumor Efficacy of Gemcitabine and Suppresses Pancreatic Cancer Development by Antagonizing STAT3 Activation

“…Interestingly, we found that fraxetin can enhance the sensitivity of PCCs to the chemotherapy drug gemcitabine. Gemcitabine is accepted as the standard treatment for patients with locally or metastatic advanced PDA, but the problem of its drug resistance has become increasingly prominent [39]. How to solve the weakening of its anti-tumor effect due to drug resistance is an important task now.…”

Does the Microenvironment Hold the Hidden Key for Functional Precision Medicine in Pancreatic Cancer?

“…Furthermore, most PDX models involve subcutaneous implantation of patient tumour tissue into immune-compromised mice which is a poor representation of the tumour microenvironment and low take rates can bias more aggressive disease [ 26 ]. Recently, organoids have gained much traction as a rapid and efficient model of interpatient heterogeneity with potential to guide functional precision medicine for PDAC [ 27 , 28 ].…”

“…Despite the many advantages of the tumour organoid model, many of the microenvironmental features discussed above are not recapitulated. Several studies have recently attempted to co-culture organoids with CAFs or immune cells, as reviewed recently [ 27 , 28 ], but the CAFs added to the organoids are not matched to the same patient and these co-culture systems also lack the presence of an ECM that matches human disease.…”

Endoscopic Ultrasound-Guided Sampling for Personalized Pancreatic Cancer Treatment

“…They showed PDOS drug screening with 100% sensitivity, 93% specificity, 88% positive predictive value, and 100% negative predictive value in forecasting response to targeted agents or chemotherapy in patients [ 16 ]. Several pilot studies on PDAC drug screening related to clinical data have been vigorously pursued based on this milestone study [ 56 , 62 , 77 ]. The report by Tiriac et al is currently the largest study of drug screening using PDOs [ 62 ].…”

“…In addition, Frappart et al also reported a drug screening study for 22 anticancer drugs in patients with PDAC [ 77 ]. In the representative cases presented in this study, the screening test result was clarified five days after the initial treatment of FORFIRINOX for metastatic PDAC.…”