Translational Medicine
Open Access
ISSN: 2161-1025
+44 1223 790975
ISSN: 2161-1025
+44 1223 790975
Jose M. Silva
AcceptedAbstracts: Transl Med
One of the major challenges for modern cancer treatments is the ability to eliminate tumor cells without affecting normal cell homeostasis. We propose to identify the �Achilles� heel� of cancer cells using the novel concept of the �non-cancer addition�. Additionally to alterations in bona-fide cancer genes, in a tumor cell, multiple normal regulatory networks have been rearranged in order to adapt to the tumorigenic state. As consequence of this divergence, survival of cancer cells also depends on non- cancer genes that are essential to maintain the tumor homeostasis. Therefore, we postulate that interfering with these non-cancer dependencies will result in system failure, that is, the cessation of the tumorigenic state. We are using the state-of-the-art RNAi- genetic approaches to block the function of every gene in the entire genome to find genetic synthetic lethal interactions between non-cancer genes and bona-fide cancer genes. The use of our pioneering RNA interference (RNAi) technology to exanimate this novel genetic concept represents a highly innovative approach that could dramatically influence the design of cancer treatments. Recently, we have applied this strategy searching for novel therapeutic alternatives for ErbB2 positive breast cancer patients. ErbB2 is a receptor tyrosine kinase found overexpressed in 20-40% of breast tumors (ErbB2+ tumors) and correlates with poor prognosis. Different targeted therapies have been developed to specifically inhibit its activity. Unfortunately, the majority of these patient tumors eventually progress acquiring resistance. Thus, there is the need to find alternative tumor targets to develop specific, more efficient, treatments for these patients. By combining genome-wide RNAi loss-of-function screens with system biology interactome models we have recently found that the JAK/STAT3 pathway is activated in ErbB2 overexpressing breast cancers through an autocrine loop mediated by the secretion of Interleukin-6 (IL-6). Importantly, blockage of this pathway strongly reduced the viability of ErbB2+ cancer cells. The identification of Stat3 as a tumor target in ErbB2+ tumors opens new avenues for patients which tumors have become refractory to standard protocols.
Jose Silva is an assistant professor at the Irving Cancer Research Center of Columbia University. He has authored more than 50 publications in reputed journals. He has pioneered the development of RNAi genetic tools to perform loss-of-function studies at a genome wide level in mammalian cells. Currently, his work is focused on using this state-of-the art RNAi technology for identification of oncogene an non-oncogene addictions in breast cancer cells as anticancer strategy.