Speaker
Description
In the last twenty years, the systemic cytotoxic chemotherapy approach left gradually place to a more personalized clinical concept, aiming to identify and target tumor peculiarities which make one tumor different from another. The lack of coherence between experimental results and in vivo effectiveness confirmed the limitation of using clonal 2D cell cultures to predict the efficacy of compounds in clinical applications. To overcome this model inadequacy, mainly in non-small cell lung cancer (NSCLC) classified as a complex disease with intra- and inter-tumor heterogeneity, the use of patient-derived tumor organoids could be an encouraging tool for precision medicine, due to model ability in retaining most of the original phenotype and genotype.
Our early-stage NSCLC organoids collection (PDO), enriched in both tumor and healthy cultures from each patient, accounts for almost 200 cases. A subset of PDOs has been widely characterized, recalling primary tissue traits and native genomic alterations, even after long-term cultures and freezing/thawing processing.
Drug sensitivity tests revealed extreme variability in PDO responses to a spectrum of compounds used in NSCLC clinical practice, including platinum-derivates and anti-folate agents. Differential responses were also identified when PDO, harboring well defined gene alterations, were treated with corresponding target drugs, confirming that the only presence of the same mutation does not guarantee uniform therapeutic efficacy. Likewise, in vitro testing of PDOs with the same chemotherapeutic compounds administered in vivo, reflected the patients’ clinical response.
Tumor organoids represent a promising in vitro model to study NSCLC complexity and to predict patients’ clinical outcomes.