Abstract IA010: Patient-derived and genetically engineered models of Ductal Carcinoma in Situ


 Ductal Carcinoma in Situ (DCIS) is a non-invasive non-obligate precursor of invasive breast cancer (IBC). DCIS is usually treated by surgery combined with radiotherapy, which can have a large impact on the life of patients. However, many of these DCIS lesions would never progress into IBC. To reduce the overtreatment of DCIS, but assure proper treatment for high-risk DCIS, it is crucial to understand the biology underlying DCIS. Therefore, we established patient-derived xenograft (PDX) mouse models of DCIS by intraductally injecting patient DCIS material into the mammary ducts of female immunocompromised mice. In addition, we used somatic engineering approaches to establish genetically engineered rat models of DCIS. Together, these preclinical in vivo model platforms enable us to (i) identify biomarkers able to distinguish high-risk from low-risk DCIS, (ii) functionally validate candidate DCIS genes, (iii) study the contribution of tumor cell-intrinsic and -extrinsic processes to DCIS progression, and (iv) study the response to targeted therapeutics.
 Citation Format: Jos Jonkers. Patient-derived and genetically engineered models of Ductal Carcinoma in Situ [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr IA010.