Breast cancer: organoids to develop more effective drugs

Obtained for the first time from metastases, with organoids it will be possible to develop targeted and effective drugs

di Beatrice Passarelli

August 4, 2022 - The breast cancer it is the most frequent neoplasm in women and in 6-7% of cases it is already metastatic at diagnosis. Metastases are responsible for 90% of all cancer deaths, including breast cancer. Studying them, therefore, is an increasingly urgent need in the therapeutic management of patients with breast cancer.

In this direction has moved the Molecular Medicine and Biotechnology Laboratory ofUniversità Campus Bio-Medico di Roma which, thanks to a lively and fruitful collaboration, which lasted about two years, with theTranslational Oncological Research Unit of the IRCCS Regina Elena National Cancer Institute (IRE) and other prestigious Italian research groups, conducted the research "A PIK3CA-mutant breast cancer metastatic patient-derived organoid approach to evaluate alpelisib treatment for multiple secondary lesions", published in the journal Molecular Cancer (IF JCR >41) and of which la Dr. Sara Donzelli (IRE) and the dr. Mario Cioce (UCBM).

Researchers have shown that it is possible to create three-dimensional cell cultures, calls organoids, from breast cancer metastases located in the brain, liver, bone, lung, skin and treat them quickly with drugs aimed at the common molecular lesion, regardless of the site of metastasis.

Organoids represent a kind of miniature tumour which faithfully reflects, in terms of transcriptional, mutational and proteomic profile, the tumor lesions from which it originated and in part also the histological complexity of the individual metastases.

Given that metastatic disease is the leading cause of treatment failure and mortality, this approach can represent a new and powerful weapon to fight tumors, allowing the pharmaceutical industry and individual oncologists to develop increasingly targeted and effective therapies and protocols.

"The importance of this work – explains the doctor. Mario Cioce - lies in the fact that, for the first time, appropriate experimental conditions have been identified to grow, with high efficiency, organoids from metastatic material and in a patient-specific manner. The use of metastatic material to make these cultures is an important innovation, together with the demonstrated possibility of being able to treat these structures by targeting the molecular lesion that supports them".

A further step forward, therefore, towards the most advanced frontier of precision medicine, applied to a real therapeutic dilemma such as breast cancer metastases.

"Having direct information from metastases, responsible for tumor progression and negative outcome of therapy, provides an even more powerful weapon to predict tumor evolution and response to therapy, to choose more valid and specific approaches for the individual patient . This great opportunity for scientific progress also represents a shining example of collaboration between heterogeneous and multidisciplinary research groups from Rome, Milan and Padua”concluded the teacher. Vito Michele Fazio, director of the Laboratory of Molecular Medicine and Biotechnology UCBM, which for years has been dealing with the intra-tumor heterogeneity of neoplastic cells and with the identification of molecular traits that condition the metastasis process in order to identify therapeutic targets.