Final Report Summary - KIDNEY CANCER (Molecular mechanisms underlying control of renal epithelial proliferative homeostasis)
This research project investigated the molecular and cellular mechanisms that underlying the formation of clear cell renal cell carcinoma and in the context of this research goal it also involved the generation of two new approaches that facilitate the generation of new mouse models of cancer and facilitate the identification of appropriate therapeutic targets. The major findings of this research are:
1. Development of the first mouse models that develop cystic and neoplastic renal carcinoma precursor lesions and identification of the genetic dependency of the initiation of these lesions on the Hif-1α and Hif-2 α transcription factors (EMBO Mol. Med. 2013, JASN 2015, Cancer Research, 2016)
2. Development of the first autochthonous mouse model of clear cell renal cell carcinoma (manuscript in preparation)
3. Establishment of a new experimental workflow based on primary mouse renal epithelial cells that allows the reverse engineering of different molecular forms of clear cell renal cell carcinoma. This research identified the involvement of the Myc oncogene in cooperative cellular transformation together with Vhl and Trp53 mutations (manuscript in preparation).
4. Establishment of a high throughput genetic system allowing combinatorial somatic genetics and its use to generate a series of autochthonous metastatic pleomorphic sarcoma models (JCI 2015)
5. Development of a lentiviral library-based screening system and identification of CK2 as a novel therapeutic target for PTEN deficient prostate carcinoma (Nature Communications 2015).
1. Development of the first mouse models that develop cystic and neoplastic renal carcinoma precursor lesions and identification of the genetic dependency of the initiation of these lesions on the Hif-1α and Hif-2 α transcription factors (EMBO Mol. Med. 2013, JASN 2015, Cancer Research, 2016)
2. Development of the first autochthonous mouse model of clear cell renal cell carcinoma (manuscript in preparation)
3. Establishment of a new experimental workflow based on primary mouse renal epithelial cells that allows the reverse engineering of different molecular forms of clear cell renal cell carcinoma. This research identified the involvement of the Myc oncogene in cooperative cellular transformation together with Vhl and Trp53 mutations (manuscript in preparation).
4. Establishment of a high throughput genetic system allowing combinatorial somatic genetics and its use to generate a series of autochthonous metastatic pleomorphic sarcoma models (JCI 2015)
5. Development of a lentiviral library-based screening system and identification of CK2 as a novel therapeutic target for PTEN deficient prostate carcinoma (Nature Communications 2015).