Charles Rudin, M.D., PhD.
My laboratory focuses on the development of novel treatment for lung cancer, the leading cancer killer of both men and women. We are investigating a variety of approaches, including inducing re-expression of genes silenced in cancer, targeting of cancer cell death pathways, systemic administration of a cancer-specific virus, and targeting of embryonic developmental signaling pathways. These are investigated (1) at a mechanistic level in cell lines and in vitro systems, (2) at a preclinical level in transgenic and xenograft models of lung cancer, and (3) at the clinical level, through early phase treatment trials in lung cancer patients.
Graduate students in the laboratory generally choose a novel therapeutic strategy to pursue, and while the primary focus of their work is likely to be in the first 2 of these 3 levels of investigation, they also have the opportunity to participate actively in translational clinical research as well.
- Rudin CM, Poirier JT, Senzer NN, Stephenson J, Loesch D, Burroughs KD, Reddy PS, Hann CL, Hallenbeck PL. Phase I clinical study of Seneca Valley Virus (SVV-001), a replication-competent picornavirus, in advanced solid tumors with neuroendocrine features. Clin Cancer Res 2011; 17:888-95.
- Gandhi L, Camidge DR, Ribeiro de Oliveira M, Bonomi P, Gandara D, Khaira D, Hann CL, McKeegan EM, Litvinovich E, Hemken PM, Dive C, Enschede SH, Nolan C, Chiu Y-L, Busman T, Xiong H, Krivoshik AP, Humerickhouse R, Shapiro GI, Rudin CM. A phase I study of Navitoclax (ABT-263), a novel Bcl-2 family inhibitor, in subjects with small cell lung cancer and other solid tumors. J Clin Oncol 2011; 29:909-16.
- Graham RA, Lum BL, Cheeti S, Jin JY, Jorga K, Von Hoff DD, Rudin CM, Reddy JC, Low JA, LoRusso PM. Pharmacokinetics of hedgehog pathway inhibitor GDC-0449 in patients with refractory locally advanced or metastatic solid tumors: the role of alpha-1-acid glycoprotein binding. Clin Cancer Res 2011; 17:2512-20.
- LoRusso PM, Rudin CM, Reddy JC, Tibes R, Weiss GL, Borad MJ, Hann CL, Brahmer JR, Chang I, Darbonne WC, Graham RA, Zerivitz KL, Low JA, Von Hoff DD. Phase I trial of hedgehog pathway inhibitor GDC-0449 in patients with refractory, locally advanced or metastatic solid tumors. Clin Cancer Res 2011; 17:2502-11.
- Rudin CM, Mauer A, Smakal M, Juergens R, Spelda S, Wertheim M, Coates A, McKeegan E, Ansell P, Zhou X, Qian J, Pradhan R, Dowell B, Krivoshik A, Gordon G. A phase I/II study of pemetrexed with or without ABT-751 in advanced or metastatic non-small cell lung cancer. J Clin Oncol 2011; 29:1075-82.
- Aftab BT, Dobromilskaya I, Liu JO, Rudin CM. Itraconazole inhibits angiogenesis and tumor growth in non-small cell lung cancer. Cancer Res 2011; 71:6764-72.
- Juergens RA, Wrangle J, Vendetti FP, Murphy SC, Zhao M, Coleman B, Sebree R, Rodgers K, Hooker CM, Franco N, Lee B, Tsai S, Delgado IE, Rudek MA, Belinsky SA, Herman JG, Baylin SB, Brock MV, Rudin CM. Combination epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancer Cancer Discovery 2011; 1:598-607.
- Shi W, Nacev BA, Aftab BT, Head S, Rudin CM, Liu J. Itraconazole side chain analogues: structure-activity relationship studies for inhibition of endothelial cell proliferation, vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, and hedgehog signaling. J Med Chem 2011; 54:7363-74.
- Osanyingbemi-Obidi J, Dobromilskaya I, Illei PB, Hann CL, Rudin, CM. Notch signaling contributes to lung cancer clonogenic capacity in vitro but may be circumvented in tumorigenesis in vivo. Mol Cancer Res 2011; 9:1746-54.
- Chena V, Hu C, Pramanik D, Aftab BT, Karikari C, Campbell NR, Hong S-M, Zhao M, Rudek MA, Khan SR, Rudin CM, Maitra A. A polymeric nanoparticle encapsulated small molecule inhibitor of hedgehog signaling (NanoHHI) bypasses secondary mutational resistance to Smoothened antagonists. Mol Cancer Ther 2012; 11:165-73.
- Tran PT, Shroff E, Thijagarajan S, Burns T, Das S, Zabuawala T, Chen J, Cho Y-J, Luong R, Tamayo P, Salih T, Aziz K, Adam S, Vincent S, Nielsen C, Withofs N, Sweet-Corder0 A, Gambhir S, Rudin CM, Felsher DW. Twist1 suppresses senescence programs and thereby accelerates and maintains mutant Kras-induced lung tumorigenesis. PLoS Genetics 2012 e1002650.
- Rudin CM, Hann CL, Garon EB, Ribeiro de Oliveira M, Bonomi PD, Camidge DR, Chu Q, Giaccone G, Khaira D, Ramalingam SS, Ranson MR, Dive C, McKeegan EM, Chyla BJ, Dowell BJ, Chakravartty A, Nolan CE, Rudersdorf N, Busman TA, Mabry MH, Krivoshik AP, Humerickhouse RA, Shapiro GI, Gandhi L. Phase 2 study of single agent navitoclax (ABT-263) and biomarker correlates in patients with relapsed small cell lung cancer. Clin Cancer Res 2012; 18:3163-9.
- Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, Solomon JA, Yoo S, Arron ST, Freidlander PA, Marmur E, Rudin CM, Chang ALS, Low JA, Mackey HM, Yauch RL, Graham RA, Reddy JC, Hauschild A. Efficacy and safety of vismodegib in advanced basal cell carcinoma. N Engl J Med 2012; 366:2171-9.
- Zeng J, Aziz K, Chettiar ST, Aftab BT, Armour M, Gajula R, Gandhi N, Salih T, Herman JM, Wong J, Rudin CM, Tran PT, Kales RK. Hedgehog pathway inhibition radiosensitizes non-small cell lung cancers. Int J Rad Onc Bio Phys 2012 (in press).
- Rudin CM, Durinck S, Stawiski E, Poirier JT, Modrusan Z, Shames D, Bergbower EA, Guan Y, Shin J, Guillory J, Sanchez Rivers C, Foo C, Dhatt D, Stinson J, Gnad F, Haverty PM, Gentleman R, Chaudhuri S, Janakiraman V, Jaiswal B, Parikh C, Yuan W, Zhang Z, Koeppen H, Wu TD, Stern HM, Yauch RL, Huffman KE, Paskulin DD, Illei PB, Varella-Garcia M, Gazdar AF, de Sauvage FJ, Bourgon R, Minna JD, Brock MV, Seshagiri S. Comprehensive genomic and expression profiling of small cell lung cancers identifies SOX2 as a frequently amplified gene regulating proliferation and correlating with clinical stage. Nat Genet 2012 (in press)