Published ahead of print last week in Cell, a study led by Carlos Caldas, Cancer Research UK Cambridge Institute, first authored by Alejandra Bruna from the same institute, and carried out in collaboration with VHIO researchers and colleagues from other cancer research center of excellence, describes a powerful new platform that can rapidly test over 100 different anti-cancer therapies at the same time and in different combinations using preclinical breast cancer models.
Findings evidence the promise of a´live´biobank of patient-derived xenograft (PDX) mouse models generated for the mass screening of anti-cancer therapies in conditions preserving tumor genomic and microenvironmental heterogeneity of human breast cancers. Violeta Serra, Principal Investigator of VHIO´s Experimental Therapies Group, and Javier Cortés, Associate Translational Investigator of VHIO´s Breast Cancer and Melanoma Group – led by Cristina Saura, and Medical Oncologist and Head of the Breast Cancer and Gynecological Tumors of Service of the Ramón and Cajal University Hospital (Madrid), as internationally renowned experts in PDX models and the clinical development of targeted therapies against breast cancer, both co-authored this important study.
This multi-center collaboration successfully generated a biobank comprising 83 PDX breast cancer models, representative of both the majority of identified subtypes of breast cancer as well as the clinical and molecular diversity of the disease.
“We have shown that despite the successive transplantation of tumors in mice, both the genetic characteristics and tumor cell morphology of the original tumor are maintained – namely its histology, tumor cell composition, and the same genetic heterogeneity associated with breast cancers. PDX models therefore recapitulate the most important biological characteristics of human cancer and consequently represent optimal predictive preclinical cancer models,” observes Violeta Serra.
The second key aspect of this study was the generation of ex vivo cell cultures from cells which retained the molecular characteristics of the original tumors. Moreover, these ex vivo cell models proved their value as a powerful and novel tool for high-throughput mass screening and determining tumor response to various anti-cancer agents either as monotherapy or in combination.
“This approach represents a significant forward step in pharmacogenomics since it enables us to test many more agents and different combinations at the same time. Importantly too, as we strive to collectively advance cancer research and medicine across borders, our data is completely open access so that colleagues elsewhere around the world can both consult and benefit from our data,” concludes Violeta.
The authors used ex vivo cell culture models to test over 100 compounds. They selected 40 positive responses to be assayed in 8 different PDX models. In 82.5% of cases, PDX and ex vivo models showed the same pharmacological response, validating the predictive value of this novel screening program using patient-derived models.
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