|Name:||Andy Minn, M.D., Ph.D.|
|Title/Titles:||Assistant Professor, Radiation Oncology
Abramson Family Cancer Research Institute
The two most daunting obstacles in the clinical management of cancer are metastasis, or the spread of tumor cells from its origin to distant sites in the body, and resistance to chemotherapy and/or radiation, which are two primary means of treating the disease. Unfortunately, the molecular mechanisms that drive these central and elusive problems in oncology have remained poorly understood. Our laboratory is focused on understanding how cancer cells acquire metastatic and treatment resistant phenotypes. Recent evidence suggests that these two traits are acquired during tumorigenesis by antagonistic forces encountered as tumors grow and interact with their environment. Key among these selective pressures include inflammation, overcoming senescence and apoptosis, and barriers imposed by surrounding stroma. Because the biology of these selective pressures can overlap with molecular mechanisms involved in metastasis and treatment resistance, genetic alterations that occur as a response to these pressures may predispose tumors to acquire a metastatic and/or treatment-resistant phenotype.
In order to better understand the basis for metastasis and treatment resistance, we utilize a multi-disciplinary approach towards both experimental and translational research goals. Hypothesis generation and testing relies on a systems biology paradigm that incorporates animal models, molecular biology, genomics, bioinformatics, and clinical correlation. Using these methods we and colleagues have identified gene expression signatures and signaling pathways that not only predict but also regulate cancer phenotypes such as aggressive organ-selective metastasis and resistance to DNA damaging agents (chemotherapy and radiation). Some of these signatures and pathways are expressed across multiple common human cancers including breast and brain cancer. Genes that regulate the expression or function of the signatures include microRNAs, interferon-related genes, and ubiquitin modifiers. Thus, gene signatures and the signaling pathways that control them point toward relevant biology that can be dissected and provide clinical tools for prognosis, prediction, and potential therapeutic targeting.
View Minn biographical sketch
Ishwaran Hemant, Kogalur Udaya B, Gorodeski Eiran Z, Minn Andy J, Lauer Michael S: High Dimensional Variable Selection for Survival Data. Journal of the American statistical association 105: 205-17, March 2010.
Bos Paula D, Zhang Xiang H-F, Nadal Cristina, Shu Weiping, Gomis Roger R, Nguyen Don X, Minn Andy J, van de Vijver Marc J, Gerald William L, Foekens John A, Massagué Joan: Genes that mediate breast cancer metastasis to the brain. Nature 459(7249): 1005-9, Jun 2009.
Dangi-Garimella Surabhi, Yun Jieun, Eves Eva M, Newman Martin, Erkeland Stefan J, Hammond Scott M, Minn Andy J, Rosner Marsha Rich: Raf kinase inhibitory protein suppresses a metastasis signalling cascade involving LIN28 and let-7. The EMBO journal 28(4): 347-58, Feb 2009.
Weichselbaum Ralph R, Ishwaran Hemant, Yoon Taewon, Nuyten Dimitry S A, Baker Samuel W, Khodarev Nikolai, Su Andy W, Shaikh Arif Y, Roach Paul, Kreike Bas, Roizman Bernard, Bergh Jonas, Pawitan Yudi, van de Vijver Marc J, Minn Andy J: An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer. Proceedings of the National Academy of Sciences of the United States of America 105(47): 18490-5, Nov 2008.
Martin Richard W, Orelli Brian J, Yamazoe Mitsuyoshi, Minn Andy J, Takeda Shunichi, Bishop Douglas K: RAD51 up-regulation bypasses BRCA1 function and is a common feature of BRCA1-deficient breast tumors. Cancer research 67(20): 9658-65, Oct 2007.
Khodarev Nikolai N, Minn Andy J, Efimova Elena V, Darga Thomas E, Labay Edwardine, Beckett Michael, Mauceri Helena J, Roizman Bernard, Weichselbaum Ralph R: Signal transducer and activator of transcription 1 regulates both cytotoxic and prosurvival functions in tumor cells. Cancer research 67(19): 9214-20, Oct 2007.
Minn Andy J, Gupta Gaorav P, Padua David, Bos Paula, Nguyen Don X, Nuyten Dimitry, Kreike Bas, Zhang Yi, Wang Yixin, Ishwaran Hemant, Foekens John A, van de Vijver Marc, Massagué Joan: Lung metastasis genes couple breast tumor size and metastatic spread. Proceedings of the National Academy of Sciences of the United States of America 104(16): 6740-5, Apr 2007.
Le Hong-Van, Minn Andy J, Massagué Joan: Cyclin-dependent kinase inhibitors uncouple cell cycle progression from mitochondrial apoptotic functions in DNA-damaged cancer cells. The Journal of biological chemistry 280(36): 32018-25, Sep 2005.
Minn Andy J, Gupta Gaorav P, Siegel Peter M, Bos Paula D, Shu Weiping, Giri Dilip D, Viale Agnes, Olshen Adam B, Gerald William L, Massagué Joan: Genes that mediate breast cancer metastasis to lung. Nature 436(7050): 518-24, Jul 2005.
Minn Andy J, Kang Yibin, Serganova Inna, Gupta Gaorav P, Giri Dilip D, Doubrovin Mikhail, Ponomarev Vladimir, Gerald William L, Blasberg Ronald, Massagué Joan: Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors. The Journal of clinical investigation 115(1): 44-55, Jan 2005.