William Pao, M.D., Ph.D.
Cornelius Abernathy Craig Professor of Medical & Surgical Oncology
Professor and Director of Hematology/Oncology
Professor of Cancer Biology and Pathology/Microbiology/Immunology
Director, Personalized Cancer Medicine
Patient Contact Information:
Henry-Joyce Cancer Clinic
1301 Medical Center Drive, Suite 1710
Nashville, Tennessee 37232-7415
Phone: 615-936-8422 or 1-877-936-8422
Healthcare Provider Contact Information:
2220 Pierce Avenue
777 Preston Research Building
Nashville, TN 37232-6307
Dr. Pao is a physician-scientist with a special interest in thoracic oncology. Dr. Pao's research focuses on identification of genes involved in the pathogenesis of lung tumors and stratifying tumors into clinically relevant molecular subsets. Using information derived from these experiments, Dr. Pao seeks to improve treatment for patients with non-small cell lung cancer. His research has yielded important insights into mechanisms of lung tumor sensitivity and resistance to inhibitors of the epidermal growth factor receptor.
Dr. Pao is the author of over 50 publications, is actively involved innumerous professional associations including the American Association for Cancer Research (AACR) and the American Society of Clinical Oncology (ASCO), and has served as a journal editor for PLoS Medicine, Cancer Research, and the Journal of Clinical Oncology.
The Pao Laboratory aims to perform translational research in the area of solid tumor biology, using lung cancer as a paradigm. The overall goal is to develop molecularly-tailored treatments for patients with lung cancer.
Lung cancer is the leading cause of cancer-related death in the U.S and worldwide. Most cases arise in former or current smokers, but about 10% of cases also occur in individuals who smoked less than 100 cigarettes in a lifetime (“never smokers”). Lung cancers are currently classified by histopathological techniques as either small-cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC). In North America, adenocarcinoma (a type of NSCLC) is the most frequent type of histological tumor, accounting for 40% of all cases of lung cancer.
New “targeted” epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) like gefitinib (Iressa) and erlotinib (Tarceva) have given us a window of opportunity to elucidate clinically relevant molecular subsets of lung adenocarcinomas. For example, clinical trials have shown that gefitinib has an overall response rate of 10% in American and European populations, and 28% in Japanese patients. Retrospective analyses suggested that gefitinib is most efficacious in “never smokers” with adenocarcinoma histology. Such findings can now be largely accounted for by research from our group and others showing the relatively high incidence of mutations in the gene encoding EGFR in these respective populations and the association of EGFR mutations with increased sensitivity to both gefitinib and erlotinib.
While EGFR mutations are common in tumors from never smokers, mutations in KRAS, which encodes a signaling molecule downstream of EGFR, more commonly occur in individuals with substantial cigarette use. Moreover, EGFR and KRAS mutations appear to be mutually exclusive, suggesting that EGFR and KRAS mutations within lung epithelia are equivalent in their tumorigenic effects. We found that mutations in KRAS are associated with primary resistance to these drugs. This suggests that pre-treatment mutational profiling of both EGFR and KRAS may help guide treatment decisions regarding the use of these agents.
Unfortunately, virtually all patients who initially respond to gefitinib and erlotinib eventually develop acquired resistance. We have shown that tumor cells from patients whose disease progresses after initial responses on therapy with these agents frequently harbor second-site mutations in EGFR. The predominant second mutation substitutes methionine for threonine at position 790 in EGFR, which is predicted to block binding of gefitinib and erlotinib to the ATP-binding pocket of the kinase. Interestingly, the T790M amino acid change is analogous to changes seen in other kinases targeted by a related kinase inhibitor, imatinib (Gleevec), in patients that develop acquired resistance to that drug. Using a genomic approach, we have also recently found that tumor samples from patients with acquired resistance to gefitinib or erlotinib harbor amplification of MET, which encodes another tyrosine kinase. MET amplification appears to occur independently of T790M mutations. Importantly, MET inhibitors are currently being developed in the clinic.
The Pao Laboratory is now focused on the following:
1) Defining further molecular subsets of lung cancers, based primarily upon mutational profiling of the oncogenome in tumor samples.
2) Elucidating other mechanisms of sensitivity and resistance to EGFR inhibitors in lung cancer. For example, we recently showed that in drug-sensitive EGFR mutant lung cancer cells, induction of BIM is essential for apoptosis triggered by EGFR kinase inhibitors. These data imply that the intrinsic pathway of caspase activation may influence sensitivity and/or resistance of EGFR mutant lung tumor cells to EGFR kinase inhibition.
3) Identifying ways to overcome resistance to gefitinib and erlotinib. We have generated mouse lung tumor models driven by EGFR T790M mutants and which are resistant to erlotinib. We are now using these models to uncover agents and strategies that overcome acquired resistance to the T790M amino acid change.
Clincial Research Description:
The identification of genetic abnormalities that initiate and sustain cancers has paved the way to a new era of personalized anti-cancer therapies which are more effective than current approaches with fewer side effects. We aim to shape the practice of cancer medicine, envisioning a day when anti-cancer treatment will be assigned according to the genetic makeup of patients' tumors rather than on an empiric basis.
- Ohashi, K, Sequist, LV, Arcila, ME, Lovly, CM, Chen, X, Rudin, CM, Moran, T, Camidge, DR, Vnencak-Jones, CL, Berry, L, Pan, Y, Sasaki, H, Engelman, JA, Garon, EB, Dubinett, SM, Franklin, WA, Riely, GJ, Sos, ML, Kris, MG, Dias-Santagata, D, Ladanyi, M, Bunn, PA, Pao, W Characteristics of Lung Cancers Harboring NRAS Mutations. Clin Cancer Res, 19(9), 2584-2591, 2013.
- Abramson, RG, Abramson, VG, Chan, E, Horn, L, Keedy, VL, Pao, W, Sosman, JA Complications of targeted drug therapies for solid malignancies: manifestations and mechanisms. AJR Am J Roentgenol, 200(3), 475-83, 2013.
- Yeh, P, Chen, H, Andrews, J, Naser, R, Pao, W, Horn, L DNA-Mutation Inventory to Refine and Enhance Cancer Treatment (DIRECT): a catalog of clinically relevant cancer mutations to enable genome-directed anticancer therapy. Clin Cancer Res, 19(7), 1894-901, 2013.
- Brewer, MR, Pao, W Maximizing the benefits of off-target kinase inhibitor activity. Cancer Discov, 3(2), 138-40, 2013.
- Jia, P, Jin, H, Meador, CB, Xia, J, Ohashi, K, Liu, L, Pirazzoli, V, Dahlman, KB, Politi, K, Michor, F, Zhao, Z, Pao, W Next-generation sequencing of paired tyrosine kinase inhibitor-sensitive and -resistant EGFR mutant lung cancer cell lines identifies spectrum of DNA changes associated with drug resistance. Genome Res, 2013.
- Dahlman, KB, Xia, J, Hutchinson, K, Ng, C, Hucks, D, Jia, P, Atefi, M, Su, Z, Branch, S, Lyle, P, Hicks, DJ, Bozon, V, Glaspy, JA, Rosen, N, Solit, DB, Netterville, JL, Vnencak-Jones, CL, Sosman, JA, Ribas, A, Zhao, Z, Pao, W BRAF L597 mutations in melanoma are associated with sensitivity to MEK inhibitors. Cancer Discov, 2012.
- Jia, P, Li, F, Xia, J, Chen, H, Ji, H, Pao, W, Zhao, Z Consensus rules in variant detection from next-generation sequencing data. PLoS One, 7(6), e38470, 2012.
- Yatabe, Y, Pao, W, Jett, JR Encouragement to Submit Data of Clinical Response to EGFR-TKIs in Patients With Uncommon EGFR Mutations. J Thorac Oncol, 7(5), 775-6, 2012.
- Lovly, CM, Pao, W Escaping ALK inhibition: mechanisms of and strategies to overcome resistance. Sci Transl Med, 4(120), 120ps2, 2012.
- Takezawa, K, Pirazzoli, V, Arcila, ME, Nebhan, CA, Song, X, de Stanchina, E, Ohashi, K, Janjigian, YY, Spitzler, PJ, Melnick, MA, Riely, GJ, Kris, MG, Miller, VA, Ladanyi, M, Politi, K, Pao, W HER2 amplification: a potential mechanism of acquired resistance to EGFR inhibition in EGFR-mutant lung cancers that lack the second-site EGFRT790M mutation. Cancer Discov, 2(10), 922-33, 2012.
- Ohashi, K, Sequist, LV, Arcila, ME, Moran, T, Chmielecki, J, Lin, YL, Pan, Y, Wang, L, de Stanchina, E, Shien, K, Aoe, K, Toyooka, S, Kiura, K, Fernandez-Cuesta, L, Fidias, P, Yang, JC, Miller, VA, Riely, GJ, Kris, MG, Engelman, JA, Vnencak-Jones, CL, Dias-Santagata, D, Ladanyi, M, Pao, W Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1. Proc Natl Acad Sci U S A, 109(31), E2127-33, 2012.
- Xia, J, Wang, Q, Jia, P, Wang, B, Pao, W, Zhao, Z NGS catalog: A database of next generation sequencing studies in humans. Hum Mutat, 33(6), E2341-55, 2012.
- Pao, W New approaches to targeted therapy in lung cancer. Proc Am Thorac Soc, 9(2), 72-3, 2012.
- Lovly, CM, Dahlman, KB, Fohn, LE, Su, Z, Dias-Santagata, D, Hicks, DJ, Hucks, D, Berry, E, Terry, C, Duke, M, Su, Y, Sobolik-Delmaire, T, Richmond, A, Kelley, MC, Vnencak-Jones, CL, Iafrate, AJ, Sosman, J, Pao, W Routine multiplex mutational profiling of melanomas enables enrollment in genotype-driven therapeutic trials. PLoS One, 7(4), e35309, 2012.
- Levy, MA, Lovly, CM, Pao, W Translating genomic information into clinical medicine: lung cancer as a paradigm. Genome Res, 22(11), 2101-8, 2012.
- Li, J, Su, Z, Ma, ZQ, Slebos, RJ, Halvey, P, Tabb, DL, Liebler, DC, Pao, W, Zhang, B A bioinformatics workflow for variant Peptide detection in shotgun proteomics. Mol Cell Proteomics, 10(5), M110.006536, 2011.
- Ohashi, K, Pao, W A new target for therapy in squamous cell carcinoma of the lung. Cancer Discov, 1(1), 23-4, 2011.
- Su, Z, Dias-Santagata, D, Duke, M, Hutchinson, K, Lin, YL, Borger, DR, Chung, CH, Massion, PP, Vnencak-Jones, CL, Iafrate, AJ, Pao, W A platform for rapid detection of multiple oncogenic mutations with relevance to targeted therapy in non-small-cell lung cancer. J Mol Diagn, 13(1), 74-84, 2011.
- Oxnard, GR, Arcila, ME, Sima, CS, Riely, GJ, Chmielecki, J, Kris, MG, Pao, W, Ladanyi, M, Miller, VA Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation. Clin Cancer Res, 17(6), 1616-22, 2011.
- Pao, W, Iafrate, AJ, Su, Z Genetically informed lung cancer medicine. J Pathol, 223(2), 230-40, 2011.
- Janjigian, YY, Park, BJ, Zakowski, MF, Ladanyi, M, Pao, W, D''Angelo, SP, Kris, MG, Shen, R, Zheng, J, Azzoli, CG Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor EGFR mutations. J Thorac Oncol, 6(3), 569-75, 2011.
- Lovly, CM, Heuckmann, JM, de Stanchina, E, Chen, H, Thomas, RK, Liang, C, Pao, W Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors. Cancer Res, 2011.
- Rizvi, NA, Rusch, V, Pao, W, Chaft, JE, Ladanyi, M, Miller, VA, Krug, LM, Azzoli, CG, Bains, M, Downey, R, Flores, R, Park, B, Singh, B, Zakowski, M, Heelan, RT, Shen, R, Kris, MG Molecular Characteristics Predict Clinical Outcomes: Prospective Trial Correlating Response to the EGFR Tyrosine Kinase Inhibitor Gefitinib with the Presence of Sensitizing Mutations in the Tyrosine Binding Domain of the EGFR Gene. Clin Cancer Res, 17(10), 3500-6, 2011.
- Pao, W, Girard, N New driver mutations in non-small-cell lung cancer. Lancet Oncol, 12(2), 175-80, 2011.
- Janjigian, YY, Azzoli, CG, Krug, LM, Pereira, LK, Rizvi, NA, Pietanza, MC, Kris, MG, Ginsberg, MS, Pao, W, Miller, VA, Riely, GJ Phase I/II trial of cetuximab and erlotinib in patients with lung adenocarcinoma and acquired resistance to erlotinib. Clin Cancer Res, 17(8), 2521-7, 2011.
- Johnson, ML, Riely, GJ, Rizvi, NA, Azzoli, CG, Kris, MG, Sima, CS, Ginsberg, MS, Pao, W, Miller, VA Phase II Trial of Dasatinib for Patients with Acquired Resistance to Treatment with the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Erlotinib or Gefitinib. J Thorac Oncol, 6(6), 1128-31, 2011.
- Arcila, ME, Oxnard, GR, Nafa, K, Riely, GJ, Solomon, SB, Zakowski, MF, Kris, MG, Pao, W, Miller, VA, Ladanyi, M Rebiopsy of lung cancer patients with acquired resistance to EGFR inhibitors and enhanced detection of the T790M mutation using a locked nucleic acid-based assay. Clin Cancer Res, 17(5), 1169-80, 2011.
- Sengsayadeth, S, Montgomery, J, Pao, W T4 or MI. J Thorac Oncol, 6(3), 632, 2011.
- Garrett, JT, Olivares, MG, Rinehart, C, Granja-Ingram, ND, SÃ¡nchez, V, Chakrabarty, A, Dave, B, Cook, RS, Pao, W, McKinely, E, Manning, HC, Chang, J, Arteaga, CL Transcriptional and posttranslational up-regulation of HER3 (ErbB3) compensates for inhibition of the HER2 tyrosine kinase. Proc Natl Acad Sci U S A, 108(12), 5021-6, 2011.
- Zhao, B, Oxnard, GR, Moskowitz, CS, Kris, MG, Pao, W, Guo, P, Rusch, VM, Ladanyi, M, Rizvi, NA, Schwartz, LH A pilot study of volume measurement as a method of tumor response evaluation to aid biomarker development. Clin Cancer Res, 16(18), 4647-53, 2010.
- Girard, N, Lou, E, Azzoli, CG, Reddy, R, Robson, M, Harlan, M, Orlow, I, Yatabe, Y, Nafa, K, Ladanyi, M, Viale, A, Kris, MG, Riely, G, Miller, V, Klein, RJ, Matsuo, K, Pao, W Analysis of genetic variants in never-smokers with lung cancer facilitated by an Internet-based blood collection protocol: a preliminary report. Clin Cancer Res, 16(2), 755-63, 2010.
- Jackman, D, Pao, W, Riely, GJ, Engelman, JA, Kris, MG, JÃ¤nne, PA, Lynch, T, Johnson, BE, Miller, VA Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J Clin Oncol, 28(2), 357-60, 2010.
- Sun, YH, Fang, R, Gao, B, Han, XK, Zhang, JH, Pao, W, Chen, HQ, Ji, HB Comparable rate of EGFR kinase domain mutation in lung adenocarcinomas from Chinese male and female never-smokers. Acta Pharmacol Sin, 31(5), 647-8, 2010.
- Solomon, SB, Zakowski, MF, Pao, W, Thornton, RH, Ladanyi, M, Kris, MG, Rusch, VW, Rizvi, NA Core needle lung biopsy specimens: adequacy for EGFR and KRAS mutational analysis. AJR Am J Roentgenol, 194(1), 266-9, 2010.
- Yeo, WL, Riely, GJ, Yeap, BY, Lau, MW, Warner, JL, Bodio, K, Huberman, MS, Kris, MG, Tenen, DG, Pao, W, Kobayashi, S, Costa, DB Erlotinib at a dose of 25 mg daily for non-small cell lung cancers with EGFR mutations. J Thorac Oncol, 5(7), 1048-53, 2010.
- Weiss, J, Sos, ML, Seidel, D, Peifer, M, Zander, T, Heuckmann, JM, Ullrich, RT, Menon, R, Maier, S, Soltermann, A, Moch, H, Wagener, P, Fischer, F, Heynck, S, Koker, M, SchÃ¶ttle, J, Leenders, F, Gabler, F, Dabow, I, Querings, S, Heukamp, LC, Balke-Want, H, AnsÃ©n, S, Rauh, D, Baessmann, I, AltmÃ¼ller, J, Wainer, Z, Conron, M, Wright, G, Russell, P, Solomon, B, Brambilla, E, Brambilla, C, Lorimier, P, Sollberg, S, Brustugun, OT, Engel-Riedel, W, Ludwig, C, Petersen, I, SÃ¤nger, J, Clement, J, Groen, H, Timens, W, Sietsma, H, Thunnissen, E, Smit, E, Heideman, D, Cappuzzo, F, Ligorio, C, Damiani, S, Hallek, M, Beroukhim, R, Pao, W, Klebl, B, Baumann, M, Buettner, R, Ernestus, K, Stoelben, E, Wolf, J, NÃ¼rnberg, P, Perner, S, Thomas, RK Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Transl Med, 2(62), 62ra93, 2010.
- Pao, W, Iafrate, AJ, Su, Z Genetically informed lung cancer medicine. J Pathol, 2010.
- Clarke, JL, Pao, W, Wu, N, Miller, VA, Lassman, AB High dose weekly erlotinib achieves therapeutic concentrations in CSF and is effective in leptomeningeal metastases from epidermal growth factor receptor mutant lung cancer. J Neurooncol, 99(2), 283-6, 2010.
- Sun, Y, Ren, Y, Fang, Z, Li, C, Fang, R, Gao, B, Han, X, Tian, W, Pao, W, Chen, H, Ji, H Lung adenocarcinoma from East Asian never-smokers is a disease largely defined by targetable oncogenic mutant kinases. J Clin Oncol, 28(30), 4616-20, 2010.
- Price, KA, Azzoli, CG, Krug, LM, Pietanza, MC, Rizvi, NA, Pao, W, Kris, MG, Riely, GJ, Heelan, RT, Arcila, ME, Miller, VA Phase II trial of gefitinib and everolimus in advanced non-small cell lung cancer. J Thorac Oncol, 5(10), 1623-9, 2010.
- Pao, W, Chmielecki, J Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer. Nat Rev Cancer, 10(11), 760-74, 2010.
- Veeriah, S, Taylor, BS, Meng, S, Fang, F, Yilmaz, E, Vivanco, I, Janakiraman, M, Schultz, N, Hanrahan, AJ, Pao, W, Ladanyi, M, Sander, C, Heguy, A, Holland, EC, Paty, PB, Mischel, PS, Liau, L, Cloughesy, TF, Mellinghoff, IK, Solit, DB, Chan, TA Somatic mutations of the Parkinson''s disease-associated gene PARK2 in glioblastoma and other human malignancies. Nat Genet, 42(1), 77-82, 2010.
- Gao, B, Sun, Y, Zhang, J, Ren, Y, Fang, R, Han, X, Shen, L, Liu, XY, Pao, W, Chen, H, Ji, H Spectrum of LKB1, EGFR, and KRAS mutations in chinese lung adenocarcinomas. J Thorac Oncol, 5(8), 1130-5, 2010.
- Chmielecki, J, Peifer, M, Jia, P, Socci, ND, Hutchinson, K, Viale, A, Zhao, Z, Thomas, RK, Pao, W Targeted next-generation sequencing of DNA regions proximal to a conserved GXGXXG signaling motif enables systematic discovery of tyrosine kinase fusions in cancer. Nucleic Acids Res, 38(20), 6985-96, 2010.
- Redente, EF, Dwyer-Nield, LD, Merrick, DT, Raina, K, Agarwal, R, Pao, W, Rice, PL, Shroyer, KR, Malkinson, AM Tumor progression stage and anatomical site regulate tumor-associated macrophage and bone marrow-derived monocyte polarization. Am J Pathol, 176(6), 2972-85, 2010.
- Girard, N, Deshpande, C, Azzoli, CG, Rusch, VW, Travis, WD, Ladanyi, M, Pao, W Use of epidermal growth factor receptor/Kirsten rat sarcoma 2 viral oncogene homolog mutation testing to define clonal relationships among multiple lung adenocarcinomas: comparison with clinical guidelines. Chest, 137(1), 46-52, 2010.
- Chitale D*, Gong Y*, Taylor BS*, Broderick S*, Brennan C, Somwar R, Golas B, Wang L, Motoi N, Szoke J, Reinersman JM, Major J, Sander C, Seshan VE, Zakowski MF, Rusch V, Pao W, Gerald W, Ladanyi M. "An integrated genomic analysis of lung cancer reveals loss of DUSP4 in EGFR-mutant tumors.." Oncogene, (28), 2773-2783, 2009.
- Girard N, Shen R, Guo T, Zakowski MF, Heguy A, Riely GJ, Huang J, Lau C, Lash AE, Ladanyi M, Viale A, Antonescu CR, Travis WD, Rusch VW, Kris MG, Pao W. "Comprehensive genomic analysis reveals clinically relevant molecular distinctions between thymic carcinomas and thymomas.." Clinical Cancer Research, (15), 6790-6799, 2009.
- Girard N, Deshpande C, Lau C, Finley D, Rusch V, Pao W, Travis WD. "Comprehensive histologic assessment helps to differentiate multiple lung primary non-small cell carcinomas from metastases.." Am J Surg Pathol, (33), 1752-1764, 2009.
- Regales L, Gong Y, Shen R, de Stanchina E, Vivanco I, Goel A, Koutcher JA, Spassove M, Ouerfelli O, Mellinghoff IK, Zakowski MF, Politi KA, Pao W. "Dual targeting of EGFR can overcome a major drug resistance mutation in mouse models of EGFR mutant lung cancer.." J Clin Invest, (119), 3000-3010, 2009.
- Girard N, Ostrovnaya I, Lau C, Park B, Ladanyi M, Finley D, Deshpande C, Rusch V, Orlow I, Travis WD, Pao W*, Begg CB*. "Genomic and mutational profiling to assess clonal relationships between multiple non-small cell lung cancers.." Clinical Cancer Research, (15), 5184-5190, 2009.
- Gong Y, Yao E, Shen R, Goel A, Arcila M, Teruya-Feldstein J, Zakowski M, Frankel S, Peifer M, Thomas RK, Ladanyi M, and Pao W. "High expression levels of total IGF-1R and sensitivity of NSCLC cells in vitro to an anti-IGF-1R antibody (R1507).." PLoS One, (4), 7273, 2009.
- Sos ML, Fischer S, Ullrich R, Peifer M, Heuckmann JM, Koker M, Heynck S, StÃ¼ckrath I, Weiss J, Fischer F, Michel K, Goel A, Regales L, Politi KA, Perera S, Getlik M, Heukamp LC, AnsÃ©n S, Zander T, Beroukhim R, Kashkar H, Shokat KM, Sellers WR, Rauh D, Orr C, Hoeflich KP, Friedman L, Wong KK, Pao W, Thomas RK. "Identifying genotype-dependent efficacy of single and combined PI3K- and MAPK-pathway inhibition in cancer.." Proc Natl Acad Scie USA, (106), 18351-18356, 2009.
- Pao, W, Kris, MG, Iafrate, AJ, Ladanyi, M, JÃ¤nne, PA, Wistuba, II, Miake-Lye, R, Herbst, RS, Carbone, DP, Johnson, BE, Lynch, TJ Integration of molecular profiling into the lung cancer clinic. Clin Cancer Res, 15(17), 5317-22, 2009.
- Zakowski, MF, Hussain, S, Pao, W, Ladanyi, M, Ginsberg, MS, Heelan, R, Miller, VA, Rusch, VW, Kris, MG Morphologic features of adenocarcinoma of the lung predictive of response to the epidermal growth factor receptor kinase inhibitors erlotinib and gefitinib. Arch Pathol Lab Med, 133(3), 470-7, 2009.
- Sos ML, Koker M, Weir BA, Heynck S, Rabinovsky R, Zander T, Seeger JM, Weiss J, Fischer F, Frommolt P, Michel K, Peifer M, Mermel C, Girard L, Peyton M, Gazdar A, Minna JD, Garraway LA, Kashkar H, Pao W, Meyerson M, Thomas RK "PTEN loss contributes to erlotinib resistance in EGFR-mutant lung cancer by activation of Akt and EGFR.." Cancer Research, 693256-3261, 2009.
- Veeriah S, Brennan C, Meng S, Singh B, Fagin JA, Solit DB, Paty PB, Rohle D, Vivanco I, Chmielecki J, Pao W, Ladanyi M, Gerald WL, Liau L, Cloughesy TC, Mischel PS, Sander C, Taylor B, Schultz N, Major J, Heguy A, Fang F, Mellinghoff IK, Chan TA. "The tyrosine phosphatase PTPRD is a tumor suppressor that is frequently inactivated and mutated in glioblastoma and other human cancers.." Proc Natl Acad Sci USA, (106), 9435-9440, 2009.
- Bean, J, Riely, GJ, Balak, M, Marks, JL, Ladanyi, M, Miller, VA, Pao, W Acquired resistance to epidermal growth factor receptor kinase inhibitors associated with a novel T854A mutation in a patient with EGFR-mutant lung adenocarcinoma. Clin Cancer Res, 14(22), 7519-25, 2008.
- Lyustikman, Y, Momota, H, Pao, W, Holland, EC Constitutive activation of Raf-1 induces glioma formation in mice. Neoplasia, 10(5), 501-10, 2008.
- Marks, JL, Golas, B, Kirchoff, T, Miller, VA, Riely, GJ, Offit, K, Pao, W EGFR mutant lung adenocarcinomas in patients with germline BRCA mutations. J Thorac Oncol, 3(7), 805, 2008.
- Li, AR, Chitale, D, Riely, GJ, Pao, W, Miller, VA, Zakowski, MF, Rusch, V, Kris, MG, Ladanyi, M EGFR mutations in lung adenocarcinomas: clinical testing experience and relationship to EGFR gene copy number and immunohistochemical expression. J Mol Diagn, 10(3), 242-8, 2008.
- Costa, DB, Nguyen, KS, Cho, BC, Sequist, LV, Jackman, DM, Riely, GJ, Yeap, BY, Halmos, B, Kim, JH, JÃ¤nne, PA, Huberman, MS, Pao, W, Tenen, DG, Kobayashi, S Effects of erlotinib in EGFR mutated non-small cell lung cancers with resistance to gefitinib. Clin Cancer Res, 14(21), 7060-7, 2008.
- Riely, GJ, Kris, MG, Rosenbaum, D, Marks, J, Li, A, Chitale, DA, Nafa, K, Riedel, ER, Hsu, M, Pao, W, Miller, VA, Ladanyi, M Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma. Clin Cancer Res, 14(18), 5731-4, 2008.
- Pratilas, CA, Hanrahan, AJ, Halilovic, E, Persaud, Y, Soh, J, Chitale, D, Shigematsu, H, Yamamoto, H, Sawai, A, Janakiraman, M, Taylor, BS, Pao, W, Toyooka, S, Ladanyi, M, Gazdar, A, Rosen, N, Solit, DB Genetic predictors of MEK dependence in non-small cell lung cancer. Cancer Res, 68(22), 9375-83, 2008.
- Ladanyi, M, Pao, W Lung adenocarcinoma: guiding EGFR-targeted therapy and beyond. Mod Pathol, 21 Suppl 2S16-22, 2008.
- Miller, VA, Riely, GJ, Zakowski, MF, Li, AR, Patel, JD, Heelan, RT, Kris, MG, Sandler, AB, Carbone, DP, Tsao, A, Herbst, RS, Heller, G, Ladanyi, M, Pao, W, Johnson, DH Molecular characteristics of bronchioloalveolar carcinoma and adenocarcinoma, bronchioloalveolar carcinoma subtype, predict response to erlotinib. J Clin Oncol, 26(9), 1472-8, 2008.
- Azzoli, CG, Park, BJ, Pao, W, Zakowski, M, Kris, MG Molecularly tailored adjuvant chemotherapy for resected non-small cell lung cancer: a time for excitement and equipoise. J Thorac Oncol, 3(1), 84-93, 2008.
- Marks, JL, Gong, Y, Chitale, D, Golas, B, McLellan, MD, Kasai, Y, Ding, L, Mardis, ER, Wilson, RK, Solit, D, Levine, R, Michel, K, Thomas, RK, Rusch, VW, Ladanyi, M, Pao, W Novel MEK1 mutation identified by mutational analysis of epidermal growth factor receptor signaling pathway genes in lung adenocarcinoma. Cancer Res, 68(14), 5524-8, 2008.
- Marks, JL, Broderick, S, Zhou, Q, Chitale, D, Li, AR, Zakowski, MF, Kris, MG, Rusch, VW, Azzoli, CG, Seshan, VE, Ladanyi, M, Pao, W Prognostic and therapeutic implications of EGFR and KRAS mutations in resected lung adenocarcinoma. J Thorac Oncol, 3(2), 111-6, 2008.
- Yang, CH, Yu, CJ, Shih, JY, Chang, YC, Hu, FC, Tsai, MC, Chen, KY, Lin, ZZ, Huang, CJ, Shun, CT, Huang, CL, Bean, J, Cheng, AL, Pao, W, Yang, PC Specific EGFR mutations predict treatment outcome of stage IIIB/IV patients with chemotherapy-naive non-small-cell lung cancer receiving first-line gefitinib monotherapy. J Clin Oncol, 26(16), 2745-53, 2008.
- Weir, BA, Woo, MS, Getz, G, Perner, S, Ding, L, Beroukhim, R, Lin, WM, Province, MA, Kraja, A, Johnson, LA, Shah, K, Sato, M, Thomas, RK, Barletta, JA, Borecki, IB, Broderick, S, Chang, AC, Chiang, DY, Chirieac, LR, Cho, J, Fujii, Y, Gazdar, AF, Giordano, T, Greulich, H, Hanna, M, Johnson, BE, Kris, MG, Lash, A, Lin, L, Lindeman, N, Mardis, ER, McPherson, JD, Minna, JD, Morgan, MB, Nadel, M, Orringer, MB, Osborne, JR, Ozenberger, B, Ramos, AH, Robinson, J, Roth, JA, Rusch, V, Sasaki, H, Shepherd, F, Sougnez, C, Spitz, MR, Tsao, MS, Twomey, D, Verhaak, RG, Weinstock, GM, Wheeler, DA, Winckler, W, Yoshizawa, A, Yu, S, Zakowski, MF, Zhang, Q, Beer, DG, Wistuba, II, Watson, MA, Garraway, LA, Ladanyi, M, Travis, WD, Pao, W, Rubin, MA, Gabriel, SB, Gibbs, RA, Varmus, HE, Wilson, RK, Lander, ES, Meyerson, M Characterizing the cancer genome in lung adenocarcinoma. Nature, 450(7171), 893-8, 2007.
- Regales, L, Balak, MN, Gong, Y, Politi, K, Sawai, A, Le, C, Koutcher, JA, Solit, DB, Rosen, N, Zakowski, MF, Pao, W Development of new mouse lung tumor models expressing EGFR T790M mutants associated with clinical resistance to kinase inhibitors. PLoS ONE, 2(8), e810, 2007.
- Pao, W, Ladanyi, M Epidermal growth factor receptor mutation testing in lung cancer: searching for the ideal method. Clin Cancer Res, 13(17), 4954-5, 2007.
- Gong, Y, Somwar, R, Politi, K, Balak, M, Chmielecki, J, Jiang, X, Pao, W Induction of BIM is essential for apoptosis triggered by EGFR kinase inhibitors in mutant EGFR-dependent lung adenocarcinomas. PLoS Med, 4(10), e294, 2007.
- Bean, J, Brennan, C, Shih, JY, Riely, G, Viale, A, Wang, L, Chitale, D, Motoi, N, Szoke, J, Broderick, S, Balak, M, Chang, WC, Yu, CJ, Gazdar, A, Pass, H, Rusch, V, Gerald, W, Huang, SF, Yang, PC, Miller, V, Ladanyi, M, Yang, CH, Pao, W MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci U S A, 104(52), 20932-7, 2007.
- Marks, JL, McLellan, MD, Zakowski, MF, Lash, AE, Kasai, Y, Broderick, S, Sarkaria, IS, Pham, D, Singh, B, Miner, TL, Fewell, GA, Fulton, LL, Mardis, ER, Wilson, RK, Kris, MG, Rusch, VW, Varmus, H, Pao, W Mutational analysis of EGFR and related signaling pathway genes in lung Adenocarcinomas identifies a novel somatic kinase domain mutation in FGFR4. PLoS ONE, 2(5), e426, 2007.
- Gao, SP, Mark, KG, Leslie, K, Pao, W, Motoi, N, Gerald, WL, Travis, WD, Bornmann, W, Veach, D, Clarkson, B, Bromberg, JF Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas. J Clin Invest, 117(12), 3846-56, 2007.
- Milton, DT, Riely, GJ, Azzoli, CG, Gomez, JE, Heelan, RT, Kris, MG, Krug, LM, Pao, W, Pizzo, B, Rizvi, NA, Miller, VA Phase 1 trial of everolimus and gefitinib in patients with advanced nonsmall-cell lung cancer. Cancer, 110(3), 599-605, 2007.
- Riely, GJ, Kris, MG, Zhao, B, Akhurst, T, Milton, DT, Moore, E, Tyson, L, Pao, W, Rizvi, NA, Schwartz, LH, Miller, VA Prospective assessment of discontinuation and reinitiation of erlotinib or gefitinib in patients with acquired resistance to erlotinib or gefitinib followed by the addition of everolimus. Clin Cancer Res, 13(17), 5150-5, 2007.
- Milton, DT, Azzoli, CG, Heelan, RT, Venkatraman, E, Gomez, JE, Kris, MG, Krug, LM, Pao, W, Rizvi, NA, Dunne, M, Miller, VA A phase I/II study of weekly high-dose erlotinib in previously treated patients with nonsmall cell lung cancer. Cancer, 107(5), 1034-41, 2006.
- Christiani, DC, Pao, W, DeMartini, JC, Linnoila, RI, Malkinson, AM, Onn, A, Politi, KA, Sharp, M, Wong, KK, Kim, K BAC consensus conference, November 4-6, 2004: epidemiology, pathogenesis, and preclinical models. J Thorac Oncol, 1(9 Suppl), S2-7, 2006.
- Riely, GJ, Pao, W, Pham, D, Li, AR, Rizvi, N, Venkatraman, ES, Zakowski, MF, Kris, MG, Ladanyi, M, Miller, VA Clinical course of patients with non-small cell lung cancer and epidermal growth factor receptor exon 19 and exon 21 mutations treated with gefitinib or erlotinib. Clin Cancer Res, 12(3 Pt 1), 839-44, 2006.
- Pao, W Defining clinically relevant molecular subsets of lung cancer. Cancer Chemother Pharmacol, 58 Suppl 1s11-5, 2006.
- Politi, K, Zakowski, MF, Fan, PD, Schonfeld, EA, Pao, W, Varmus, HE Lung adenocarcinomas induced in mice by mutant EGF receptors found in human lung cancers respond to a tyrosine kinase inhibitor or to down-regulation of the receptors. Genes Dev, 20(11), 1496-510, 2006.
- Milton, DT, Riely, GJ, Pao, W, Miller, VA, Kris, MG, Heelan, RT Molecular on/off switch. J Clin Oncol, 24(30), 4940-2, 2006.
- Pao, W Monitoring EGFR-mutant lung cancers by means of the blood. J Thorac Oncol, 1(3), 199-200, 2006.
- Balak, MN, Gong, Y, Riely, GJ, Somwar, R, Li, AR, Zakowski, MF, Chiang, A, Yang, G, Ouerfelli, O, Kris, MG, Ladanyi, M, Miller, VA, Pao, W Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin Cancer Res, 12(21), 6494-501, 2006.
- Riely, GJ, Politi, KA, Miller, VA, Pao, W Update on epidermal growth factor receptor mutations in non-small cell lung cancer. Clin Cancer Res, 12(24), 7232-41, 2006.
- Pham, D, Kris, MG, Riely, GJ, Sarkaria, IS, McDonough, T, Chuai, S, Venkatraman, ES, Miller, VA, Ladanyi, M, Pao, W, Wilson, RK, Singh, B, Rusch, VW Use of cigarette-smoking history to estimate the likelihood of mutations in epidermal growth factor receptor gene exons 19 and 21 in lung adenocarcinomas. J Clin Oncol, 24(11), 1700-4, 2006.
- Pao, W, Miller, VA, Politi, KA, Riely, GJ, Somwar, R, Zakowski, MF, Kris, MG, Varmus, H Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med, 2(3), e73, 2005.
- Riely, GJ, Pao, W Combining EGFR targeted therapy with chemotherapy in pancreatic cancer: is timing important. Cancer Biol Ther, 4(10), 1096-7, 2005.
- Ren, GP, Wang, TY, Pan, QL, Pao, W, Huai, J Epidermal growth factor receptor mutations detected in tumors from Chinese "never smokers" with lung adenocarcinoma. Chin Med J (Engl), 118(9), 769-71, 2005.
- Pao, W, Miller, VA Epidermal growth factor receptor mutations, small-molecule kinase inhibitors, and non-small-cell lung cancer: current knowledge and future directions. J Clin Oncol, 23(11), 2556-68, 2005.
- Pao, W, Ladanyi, M, Miller, VA, , Erlotinib in lung cancer. N Engl J Med, 353(16), 1739-41; author reply 1739-41, 2005.
- Carter, TA, Wodicka, LM, Shah, NP, Velasco, AM, Fabian, MA, Treiber, DK, Milanov, ZV, Atteridge, CE, Biggs, WH, Edeen, PT, Floyd, M, Ford, JM, Grotzfeld, RM, Herrgard, S, Insko, DE, Mehta, SA, Patel, HK, Pao, W, Sawyers, CL, Varmus, H, Zarrinkar, PP, Lockhart, DJ Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases. Proc Natl Acad Sci U S A, 102(31), 11011-6, 2005.
- Pao, W, Wang, TY, Riely, GJ, Miller, VA, Pan, Q, Ladanyi, M, Zakowski, MF, Heelan, RT, Kris, MG, Varmus, HE KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med, 2(1), e17, 2005.
- Lassman, AB, Rossi, MR, Raizer, JJ, Razier, JR, Abrey, LE, Lieberman, FS, Grefe, CN, Lamborn, K, Pao, W, Shih, AH, Kuhn, JG, Wilson, R, Nowak, NJ, Cowell, JK, DeAngelis, LM, Wen, P, Gilbert, MR, Chang, S, Yung, WA, Prados, M, Holland, EC Molecular study of malignant gliomas treated with epidermal growth factor receptor inhibitors: tissue analysis from North American Brain Tumor Consortium Trials 01-03 and 00-01. Clin Cancer Res, 11(21), 7841-50, 2005.
- Varmus, H, Pao, W, Politi, K, Podsypanina, K, Du, YC Oncogenes come of age. Cold Spring Harb Symp Quant Biol, 701-9, 2005.
- Shah, NT, Kris, MG, Pao, W, Tyson, LB, Pizzo, BM, Heinemann, MH, Ben-Porat, L, Sachs, DL, Heelan, RT, Miller, VA Practical management of patients with non-small-cell lung cancer treated with gefitinib. J Clin Oncol, 23(1), 165-74, 2005.
- Pan, Q, Pao, W, Ladanyi, M Rapid polymerase chain reaction-based detection of epidermal growth factor receptor gene mutations in lung adenocarcinomas. J Mol Diagn, 7(3), 396-403, 2005.
- Pao, W, Miller, VA, Kris, MG ''Targeting'' the epidermal growth factor receptor tyrosine kinase with gefitinib (Iressa) in non-small cell lung cancer (NSCLC). Semin Cancer Biol, 14(1), 33-40, 2004.
- Miller, VA, Kris, MG, Shah, N, Patel, J, Azzoli, C, Gomez, J, Krug, LM, Pao, W, Rizvi, N, Pizzo, B, Tyson, L, Venkatraman, E, Ben-Porat, L, Memoli, N, Zakowski, M, Rusch, V, Heelan, RT Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer. J Clin Oncol, 22(6), 1103-9, 2004.
- Pao, W, Miller, V, Zakowski, M, Doherty, J, Politi, K, Sarkaria, I, Singh, B, Heelan, R, Rusch, V, Fulton, L, Mardis, E, Kupfer, D, Wilson, R, Kris, M, Varmus, H EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A, 101(36), 13306-11, 2004.
- Pao, W, Miller, VA, Venkatraman, E, Kris, MG Predicting sensitivity of non-small-cell lung cancer to gefitinib: is there a role for P-Akt. J Natl Cancer Inst, 96(15), 1117-9, 2004.
- Cong, F, Zhang, J, Pao, W, Zhou, P, Varmus, H A protein knockdown strategy to study the function of beta-catenin in tumorigenesis. BMC Mol Biol, 410, 2003.
- Zhang, F, Pao, W, Umphress, SM, Jakowlew, SB, Meyer, AM, Dwyer-Nield, LD, Nielsen, LD, Takeda, K, Gelfand, EW, Fisher, JH, Zhang, L, Malkinson, AM, Mason, RJ Serum levels of surfactant protein D are increased in mice with lung tumors. Cancer Res, 63(18), 5889-94, 2003.
- Pao, W, Klimstra, DS, Fisher, GH, Varmus, HE Use of avian retroviral vectors to introduce transcriptional regulators into mammalian cells for analyses of tumor maintenance. Proc Natl Acad Sci U S A, 100(15), 8764-9, 2003.
- Khan, KM, Pao, W, Kendler, J Epidural abscess and vertebral osteomyelitis caused by Listeria monocytogenes: case report and literature review. Scand J Infect Dis, 33(9), 714-6, 2001.
- Girard N, Ostrovnaya I, Lau C, Park B, Ladanyi M, Finley D, Deshpande C, Rusch V, Orlow I, Travis WD, Pao W*, Begg CB*. "Genomic and mutational profiling to assess clonal relationships between multiple non-small cell lung cancers.." Clinical Cancer Research, (15), 5184-5190, 2001.
- Pao, W, Duncan, KO, Bolognia, JL, Carroll, CB, Hotez, PJ, Bessen, DE Numerous eruptive lesions of panniculitis associated with group A streptococcus bacteremia in an immunocompetent child. Clin Infect Dis, 27(3), 430-3, 1998.
- Wen, L, Barber, DF, Pao, W, Wong, FS, Owen, MJ, Hayday, A Primary gamma delta cell clones can be defined phenotypically and functionally as Th1/Th2 cells and illustrate the association of CD4 with Th2 differentiation. J Immunol, 160(4), 1965-74, 1998.
- Passoni, L, Hoffman, ES, Kim, S, Crompton, T, Pao, W, Dong, MQ, Owen, MJ, Hayday, AC Intrathymic delta selection events in gammadelta cell development. Immunity, 7(1), 83-95, 1997.
- Mallick-Wood, CA, Pao, W, Cheng, AM, Lewis, JM, Kulkarni, S, Bolen, JB, Rowley, B, Tigelaar, RE, Pawson, T, Hayday, AC Disruption of epithelial gamma delta T cell repertoires by mutation of the Syk tyrosine kinase. Proc Natl Acad Sci U S A, 93(18), 9704-9, 1996.
- Pao, W, Wen, L, Smith, AL, Gulbranson-Judge, A, Zheng, B, Kelsoe, G, MacLennan, IC, Owen, MJ, Hayday, AC Gamma delta T cell help of B cells is induced by repeated parasitic infection, in the absence of other T cells. Curr Biol, 6(10), 1317-25, 1996.
- Dianda, L, Gulbranson-Judge, A, Pao, W, Hayday, AC, MacLennan, IC, Owen, MJ Germinal center formation in mice lacking alpha beta T cells. Eur J Immunol, 26(7), 1603-7, 1996.
- Wen, L, Pao, W, Wong, FS, Peng, Q, Craft, J, Zheng, B, Kelsoe, G, Dianda, L, Owen, MJ, Hayday, AC Germinal center formation, immunoglobulin class switching, and autoantibody production driven by "non alpha/beta" T cells. J Exp Med, 183(5), 2271-82, 1996.
- Cheng, AM, Rowley, B, Pao, W, Hayday, A, Bolen, JB, Pawson, T Syk tyrosine kinase required for mouse viability and B-cell development. Nature, 378(6554), 303-6, 1995.
- Kyes, S, Pao, W, Hayday, A Influence of site of expression on the fetal gamma delta T-cell receptor repertoire. Proc Natl Acad Sci U S A, 88(17), 7830-3, 1991.
- Ph.D. - Yale University, 1998
- M.D. - Yale University, 1990
- Fellowship - Memorial Sloan-Kettering Cancer Center, 2005
- Fellowship - Memorial Sloan-Kettering Cancer Center, 2004
- Internship - New York Presbyterian Hospital, 2000
- Residency - New York Presbyterian Hospital, 2000