Dissecting and Targeting Latent Metastasis
Annual rept. 1 Sep 2012-31 Aug 2013
SLOAN-KETTERING INST FOR CANCER RESEARCH NEW YORK
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The overall goal of this project is to identify genes and pathways that support the viability of LMBC in host tissues. We have made progress under each of the three Tasks planned for year 01 in the original Statement of Work. Task 1 to develop novel model systems of LMBC has been fully accomplished in year 01, as planned. From triple-negative breast tumors and HER2-positive breast tumors we have derived cell lines that abundantly proliferate in vitro but have the capacity to enter a state of long-term latency after infiltrating target organs including lungs, the bone marrow, kidneys or the brain in mice. The resulting cell lines will be subjected to analysis during year 02 in order to decipher the genes and pathways that support LMBC cells in host tissues. Task 2 to identify genes that support the viability of disseminated breast cancer cells, has been initiated in year 01 as planned. Progress includes the implementation of tagged ribosome affinity purification TRAP and, independently, the identification of genes that support the early survival of breast cancer cells that infiltrate the brain. Task 4 to establish the functional relevance of LMBC genes and pathways has also been initiated in year 01 as planned, with the identification of IGF1CXCL12 signaling as an important mechanism for the initial survival of breast cancer cells that infiltrated the bone marrow. The studies and progress in the first year therefore represent highly promising progress towards the overall goal of delineating the biology of LMBC.
- Medicine and Medical Research