A breast cancer Patient-Derived Xenograft biobank to study tumour heterogeneity and mechanisms of resistance

A study from Italian researchers of Centro di Riferimento Oncologico in Aviano, in collaboration with Fondazione Michelangelo, has been published on The Journal of Pathology and shows that a breast cancer Patient-Derived Xenograft library can be used to help in the identification and development of more successful therapies in advanced luminal breast cancer.

Authors established a comprehensive Patient-Derived Xenograft (PDX) biobank, focusing particularly on luminal estrogen receptor-positive and young premenopausal patients for whom PDX models are currently scarce, to study the high heterogeneity of these tumours and understand the molecular mechanisms driving tumor progression and drug resistance. The success rate in establishing PDX was 17% and PDX faithfully mirrored morphologic and genetic features of primitive breast cancers, serving as a reliable model to investigate drug resistance and test different therapeutic strategies. As authors say, «Our PDX models may serve as robust tools to elucidate the molecular basis of breast cancer disease progression and provide the possibility to simultaneously test different therapies on the same tumor, potentially surmounting treatment resistance». Researchers focused on mechanisms of resistance to CDK4/6 inhibitors, finding that some tumours might regrow under a treatment with palbociclib despite initial shrinkage because they become refractory to CDK4/6 inhibitor both at a biological and molecular level, with a significant enrichment in proliferation pathways; targeting of these molecular processes can be a successful strategy to overcome resistance, as showed in organoids derived from these PDX. As authors conclude, «Considering the substantial number of luminal breast cancer patients experiencing recurrence, the frequent emergence of drug resistance, and the increasing number of young patients, it is imperative to generate appropriate models to investigate resistance mechanisms and identify more effective treatment approaches. By establishing this biobank of breast cancer specimens and PDX, we have generated living tools for future basic, translational and preclinical research».