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Michael B Lilly, MD
Professor of Medicine
Hematology/Oncology
College of Medicine
MUSC

Email: lillym@musc.edu
 
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Michael B Lilly, MD

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Research Interest:

My research efforts are focused on ways to improve the care of patients with advanced prostate cancer. Cancer treatments often induce survival responses in cancer cells, resulting in limited efficacy. These survival responses are mediated in part by PIM kinases, enzymes that regulate cancer cells’ survival machinery. Current studies are looking at the biochemical events that are regulated by PIM1 kinase, using both experimental and bioinformatics approaches. These studies suggest that PIM1 regulates a network of other kinases which coordinate expression of multiple survival genes. My laboratory is also studying mutations in the PIM1 kinase that occur in cancer patients. These mutant enzymes show unique patterns of sensitivity to known PIM1 kinase inhibitors that may be relevant to the choice of cancer treatments. In addition to laboratory studies, I also conduct clinical trials in patients with advanced prostate cancer. My primary interest is in investigator-initiated, early phase clinical trials. A recent trial studied the use of dasatinib, an oral medicine that inhibits kinases (growth promoting enzymes) in cancer cells. This study documented that dasatinib has activity against advanced prostate cancer, possibly by inhibiting the expression of a tumor growth factor called IL-6. Current studies combine standard chemotherapy drugs with nutritional supplements or with antibodies that destroy tumor blood vessels. Treatment of younger patients with aggressive prostate cancer is a particular interest of mine. My clinical studies examine the potential benefits of chemotherapy treatment given immediately after surgery for young, high-risk prostate cancer patients.

Positions:
Associate Director of Translational Research, Hollings Cancer Center, Medical University of South Carolina

Selected Publications:

1.Wang L, Li W, Lin M, Garcia M, Mulholland D, Lilly M, Martins-Green M. Luteolin, Ellagic Acid and Punicic Acid are Natural Products that Inhibit Prostate Cancer Metastasis. Carcinogenesis. ., 2014.
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2.Jia Z, Lilly MB, Koziol JA, Chen X, Xia XQ, Wang Y, Skarecky D, Sutton M, Sawyers A, Ruckle H, Carpenter PM, Wang-Rodriguez J, Jiang J, Deng M, Pan C, Zhu JG, McLaren CE, Gurley MJ, Lee C, McClelland M, Ahlering T, Kattan MW, Mercola D. Generation of "virtual" control groups for single arm prostate cancer adjuvant trials. PLoS One. .9(1):e85010, 2014. PMCID: PMC3897405
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3.Twardowski PW, Beumer JH, Chen CS, Kraft AS, Chatta GS, Mitsuhashi M, Ye W, Christner SM, Lilly MB. A phase II trial of dasatinib in patients with metastatic castration-resistant prostate cancer treated previously with chemotherapy. Anticancer Drugs. .24(7):743-53, 2013.
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4.Khan S, Jutzy JM, Valenzuela MM, Turay D, Aspe JR, Ashok A, Mirshahidi S, Mercola D, Lilly MB, Wall NR. Plasma-derived exosomal survivin, a plausible biomarker for early detection of prostate cancer. PLoS One. .7(10):e46737, 2012. PMCID: PMC3473028
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5.Janes MR, Vu C, Mallya S, Shieh MP, Limon JJ, Li LS, Jessen KA, Martin MB, Ren P, Lilly MB, Sender LS, Liu Y, Rommel C, Fruman DA. Efficacy of the investigational mTOR kinase inhibitor MLN0128/INK128 in models of B-cell acute lymphoblastic leukemia. Leukemia. .27(3):586-94, 2012. PMCID: PMC3593948
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6.Li X, Liu Z, Xu X, Blair CA, Sun Z, Xie J, Lilly MB, Zi X. Kava components down-regulate expression of AR and AR splice variants and reduce growth in patient-derived prostate cancer xenografts in mice. PLoS One. .7(2):e31213, 2012. PMCID: PMC3276576
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7.Romero Rosales K, Singh G, Wu K, Chen J, Janes MR, Lilly MB, Peralta ER, Siskind LJ, Bennett MJ, Fruman DA, Edinger AL. Sphingolipid-based drugs selectively kill cancer cells by down-regulating nutrient transporter proteins. Biochem J. .439(2):299-311, 2011. PMCID: PMC3454501
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8.Kraft AS, Garrett-Mayer E, Wahlquist AE, Golshayan A, Chen CS, Butler W, Bearden J, Lilly M. Combination therapy of recurrent prostate cancer with the proteasome inhibitor bortezomib plus hormone blockade. Cancer Biol Ther. .12(2):119-24, 2011.
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9.Shieh MP, Mitsuhashi M, Lilly M. Moving on up: Second-Line Agents as Initial Treatment for Newly-Diagnosed Patients with Chronic Phase CML. Clin Med Insights Oncol. .5:185-99, 2011. PMCID: PMC3140277
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10.Tang Y, Parmakhtiar B, Simoneau AR, Xie J, Fruehauf J, Lilly M, Zi X. Lycopene enhances docetaxel's effect in castration-resistant prostate cancer associated with insulin-like growth factor I receptor levels. Neoplasia. .13(2):108-19, 2011. PMCID: PMC3033590
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11.Basu A, Banerjee H, Rojas H, Martinez SR, Roy S, Jia Z, Lilly MB, De León M, Casiano CA. Differential expression of peroxiredoxins in prostate cancer: consistent upregulation of PRDX3 and PRDX4. Prostate. .71(7):755-65, 2010. PMCID: PMC3107902
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12.Cen B, Mahajan S, Zemskova M, Beharry Z, Lin YW, Cramer SD, Lilly MB, Kraft AS. Regulation of Skp2 levels by the Pim-1 protein kinase. J Biol Chem. .285(38):29128-37, 2010. PMCID: PMC2937943
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13.Zemskova M, Lilly MB, Lin YW, Song JH, Kraft AS. p53-dependent induction of prostate cancer cell senescence by the PIM1 protein kinase. Mol Cancer Res. .8(8):1126-41, 2010. PMCID: PMC3407470
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14.Lilly MB, Ottmann OG, Shah NP, Larson RA, Reiffers JJ, Ehninger G, Müller MC, Charbonnier A, Bullorsky E, Dombret H, Brigid Bradley-Garelik M, Zhu C, Martinelli G. Dasatinib 140 mg once daily versus 70 mg twice daily in patients with Ph-positive acute lymphoblastic leukemia who failed imatinib: Results from a phase 3 study. Am J Hematol. .85(3):164-70, 2010.
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15.Janes MR, Limon JJ, So L, Chen J, Lim RJ, Chavez MA, Vu C, Lilly MB, Mallya S, Ong ST, Konopleva M, Martin MB, Ren P, Liu Y, Rommel C, Fruman DA. Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor. Nat Med. .16(2):205-13, 2010. PMCID: PMC4017764
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16.Nga ME, Swe NN, Chen KT, Shen L, Lilly MB, Chan SP, Salto-Tellez M, Das K. PIM-1 kinase expression in adipocytic neoplasms: diagnostic and biological implications. Int J Exp Pathol. .91(1):34-43, 2009. PMCID: PMC2812726
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17.Mediavilla-Varela M, Pacheco FJ, Almaguel F, Perez J, Sahakian E, Daniels TR, Leoh LS, Padilla A, Wall NR, Lilly MB, De Leon M, Casiano CA. Docetaxel-induced prostate cancer cell death involves concomitant activation of caspase and lysosomal pathways and is attenuated by LEDGF/p75. Mol Cancer. .8:68, 2009. PMCID: PMC2741463
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18.Zhang F, Beharry ZM, Harris TE, Lilly MB, Smith CD, Mahajan S, Kraft AS. PIM1 protein kinase regulates PRAS40 phosphorylation and mTOR activity in FDCP1 cells. Cancer Biol Ther. .8(9):846-53, 2009.
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19.Kharas MG, Janes MR, Scarfone VM, Lilly MB, Knight ZA, Shokat KM, Fruman DA. Ablation of PI3K blocks BCR-ABL leukemogenesis in mice, and a dual PI3K/mTOR inhibitor prevents expansion of human BCR-ABL+ leukemia cells. J Clin Invest. .118(9):3038-50, 2008. PMCID: PMC2515380
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20.Shah N, Pang B, Yeoh KG, Thorn S, Chen CS, Lilly MB, Salto-Tellez M. Potential roles for the PIM1 kinase in human cancer - a molecular and therapeutic appraisal. Eur J Cancer. .44(15):2144-51, 2008.
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21.Zemskova M, Sahakian E, Bashkirova S, Lilly M. The PIM1 kinase is a critical component of a survival pathway activated by docetaxel and promotes survival of docetaxel-treated prostate cancer cells. J Biol Chem. .283(30):20635-44, 2008. PMCID: PMC3258959
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22.Zhou J, Pan M, Xie Z, Loh SL, Bi C, Tai YC, Lilly M, Lim YP, Han JH, Glaser KB, Albert DH, Davidsen SK, Chen CS. Synergistic antileukemic effects between ABT-869 and chemotherapy involve downregulation of cell cycle-regulated genes and c-Mos-mediated MAPK pathway. Leukemia. .22(1):138-46, 2007.
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23.Holder S, Lilly M, Brown ML. Comparative molecular field analysis of flavonoid inhibitors of the PIM-1 kinase. Bioorg Med Chem. .15(19):6463-73, 2007.
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24.Hansen JE, Fischer LK, Chan G, Chang SS, Baldwin SW, Aragon RJ, Carter JJ, Lilly M, Nishimura RN, Weisbart RH, Reeves ME. Antibody-mediated p53 protein therapy prevents liver metastasis in vivo. Cancer Res. .67(4):1769-74, 2007.
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25.Ma J, Arnold HK, Lilly MB, Sears RC, Kraft AS. Negative regulation of Pim-1 protein kinase levels by the B56beta subunit of PP2A. Oncogene. .26(35):5145-53, 2007.
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26.Holder S, Zemskova M, Zhang C, Tabrizizad M, Bremer R, Neidigh JW, Lilly MB. Characterization of a potent and selective small-molecule inhibitor of the PIM1 kinase. Mol Cancer Ther. .6(1):163-72, 2007.
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27.Zemskova M, Wechter W, Bashkirova S, Chen CS, Reiter R, Lilly MB. Gene expression profiling in R-flurbiprofen-treated prostate cancer: R-Flurbiprofen regulates prostate stem cell antigen through activation of AKT kinase. Biochem Pharmacol. .72(10):1257-67, 2006.
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28.Chen WW, Chan DC, Donald C, Lilly MB, Kraft AS. Pim family kinases enhance tumor growth of prostate cancer cells. Mol Cancer Res. .3(8):443-51, 2005.
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29.Kim KT, Baird K, Ahn JY, Meltzer P, Lilly M, Levis M, Small D. Pim-1 is up-regulated by constitutively activated FLT3 and plays a role in FLT3-mediated cell survival. Blood. .105(4):1759-67, 2004.
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30.Yan B, Zemskova M, Holder S, Chin V, Kraft A, Koskinen PJ, Lilly M. The PIM-2 kinase phosphorylates BAD on serine 112 and reverses BAD-induced cell death. J Biol Chem. .278(46):45358-67, 2003.
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31.Lilly MB, Zemskova M, Frankel AE, Salo J, Kraft AS. Distinct domains of the human granulocyte-macrophage colony-stimulating factor receptor alpha subunit mediate activation of Jak/Stat signaling and differentiation. Blood. .97(6):1662-70, 2001.
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32.Lilly M, Sandholm J, Cooper JJ, Koskinen PJ, Kraft A. The PIM-1 serine kinase prolongs survival and inhibits apoptosis-related mitochondrial dysfunction in part through a bcl-2-dependent pathway. Oncogene. .18(27):4022-31, 1999.
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33.Frankel AE, Lilly M, Kreitman R, Hogge D, Beran M, Freedman MH, Emanuel PD, McLain C, Hall P, Tagge E, Berger M, Eaves C. Diphtheria toxin fused to granulocyte-macrophage colony-stimulating factor is toxic to blasts from patients with juvenile myelomonocytic leukemia and chronic myelomonocytic leukemia. Blood. .92(11):4279-86, 1998.
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34.Matsuguchi T, Lilly MB, Kraft AS. Cytoplasmic domains of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor beta chain (hbetac) responsible for human GM-CSF-induced myeloid cell differentiation. J Biol Chem. .273(31):19411-8, 1998.
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