The core intellectual foundation of this application rests on a very simple and yet very novel idea not yet developed and implemented in any center in the world which we term for brevity "the Co-Clinical Project". The past years have seen tremendous advances in technology that have allowed us to gain powerful insight into the molecular and genetic determinants that drive cancer. However, by comparison, the rate at which this advanced knowledge has been translated into effective therapeutics is pitifully slow. In order to fill this void we have come up with "The Co-Clinical Project" idea. The "Co-Clinical Project" stems from the realization of the tremendous power of preclinical testing of new drugs, novel drug combinations and novel therapeutic modalities in mouse models of human cancer. In a nut-shell, what we propose with the "Co-Clinical Project" is that each clinical trial at the participating Institutions will be run "in parallel" with pre-clinical trials in appropriate, faithful and genetically relevant mouse models, and that the clinical, biological and pharmacological information (i.e. somatic mutational background, germline single nucleotide polymorphism (SNP) variations, responsiveness to specific regimens;imaging, microarray and proteomics profiles) will be accrued, analyzed in parallel and integrated in order to facilitate the identification of biomarkers that predict response to specific treatments. These studies will ultimately bring the advances in technology and our understanding of cancer to a strong translational forum, rapidly leading to patient stratification criteria based on molecular and genetic information. We describe here how this "Leadership team" envisions the factual realization of this exciting and ambitious endeavor.
This application will have a defining impact on how cancer clinical trials are designed and carried out. The development of the "Co-Clinical Trial" Project will put in place a blue print for the rapid development and subsequent translation of novel cancer therapies from bench to bedside, enabling a more coordinated and rational effort between basic research and clinical scientists towards the eradication of cancer.
|Song, Su Jung; Pandolfi, Pier Paolo (2014) MicroRNAs in the pathogenesis of myelodysplastic syndromes and myeloid leukaemia. Curr Opin Hematol 21:276-82|
|Lunardi, Andrea; Nardella, Caterina; Clohessy, John G et al. (2014) Of model pets and cancer models: an introduction to mouse models of cancer. Cold Spring Harb Protoc 2014:17-31|
|Hata, Aaron N; Yeo, Alan; Faber, Anthony C et al. (2014) Failure to induce apoptosis via BCL-2 family proteins underlies lack of efficacy of combined MEK and PI3K inhibitors for KRAS-mutant lung cancers. Cancer Res 74:3146-56|
|Song, Su Jung; Ito, Keisuke; Ala, Ugo et al. (2013) The oncogenic microRNA miR-22 targets the TET2 tumor suppressor to promote hematopoietic stem cell self-renewal and transformation. Cell Stem Cell 13:87-101|
|Corcoran, Ryan B; Cheng, Katherine A; Hata, Aaron N et al. (2013) Synthetic lethal interaction of combined BCL-XL and MEK inhibition promotes tumor regressions in KRAS mutant cancer models. Cancer Cell 23:121-8|
|Lunardi, Andrea; Ala, Ugo; Epping, Mirjam T et al. (2013) A co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer. Nat Genet 45:747-55|
|Payton, Sarah (2013) Prostate cancer: of mice and men--a co-clinical approach to CRPC. Nat Rev Urol 10:429|
|Zhao, Song; Nelson, Peter S (2013) Leveraging the species barrier to advance cancer therapy. Nat Genet 45:718-20|
|Corcoran, Ryan B; Ebi, Hiromichi; Turke, Alexa B et al. (2012) EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib. Cancer Discov 2:227-35|
|Katayama, Ryohei; Shaw, Alice T; Khan, Tahsin M et al. (2012) Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers. Sci Transl Med 4:120ra17|
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