Accession Number : ADA616398


Title :   Dissecting and Targeting Latent Metastasis


Descriptive Note : Annual rept. 1 Sep 2013-31 Aug 2014


Corporate Author : SLOAN-KETTERING INST FOR CANCER RESEARCH NEW YORK


Personal Author(s) : Massague, Joan


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a616398.pdf


Report Date : Sep 2014


Pagination or Media Count : 85


Abstract : Metastasis is physically and psychologically devastating, frequently incurable, and the cause of 90% of deaths from breast cancer. Invasive breast tumors release cancer cells from the outset, and thousands of these cells infiltrate distant organs before the primary tumor is diagnosed and removed. Microscopic cancer colonies that remain in a patient's organs after the removal of a breast tumor constitute latent metastasis of breast cancer (LMBC). These cells retain the potential to form overt metastasis for years. Targeting LMBC with new drugs offers an untapped opportunity to prevent metastasis. This research project aims at identifying the cell types, organ sites, tissue niches, metastasis genes, and signaling functions that support the survival and fitness of LMBC cells. In year 02 we made progress in isolating latent metastatic cells from breast cancer and lung cancer. We implemented transcriptional analysis of selected cancer cell populations in highly heterogeneous tumor microenvironments. We identified L1CAM as a mediator of vascular cooption by disseminated metastasis-initiating cells in different organs, and as a potential therapeutic target against metastasis. We identified connexin 43 (Cx43) and protocadherin 7 (PCDH7) as components of gap junctions that mediate survival and colony initiation in breast cancer cells that infiltrate the brain. We showed that gap junction modulators can be safely used as inhibitors of brain metastasis of breast cancer.


Descriptors :   *BREAST CANCER , *CELLS(BIOLOGY) , *METASTASIS , COLONIES(BIOLOGY) , DORMANCY , DRUGS , GENES , HETEROGENEITY , INHIBITORS , LUNG CANCER , MAMMARY GLANDS , MICROSCOPY , NEOPLASMS , ORGANS(ANATOMY) , PATIENTS , PROPAGATION , REMOVAL , SIGNALS , THERAPY


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE