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Last Name
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Daniel Botelho Costa, M.D.

TitleAssistant Professor of Medicine
InstitutionBeth Israel Deaconess Medical Center
DepartmentMedicine
AddressBeth Israel Deaconess Med Ctr
Hematology/Oncology Division, SC 913
330 Brookline Ave
Boston MA 02215
Phone617/667-9236
Fax617/975-5665

 Biography 
 awards and honors
1995 - 2000MD
2001 - 2004Intern and Resident in Internal Medicine
2004 - 2007Fellow in Hematology/Oncology
2004 - 2008PhD
2007 - 2009MMSc - Clinical Investigator Training Program
2007 - 2010Staff Physician and Instructor in Medicine
2010 - Staff Physician and Assistant Professor of Medicine

 Overview 
 overview
Lung cancer is the leading cause of death from cancer in the United States. Better understanding of oncogenes and tumor suppressor genes involved in lung cancer hold the promise of improving clinical care of afflicted patients.

Prior work from our group has focused on transcription factors involved in lung cancer and mechanisms of sensitivity/resistance of oncogene kinases (such as EGFR, ALK, KRAS, ROS1) to tyrosine kinase inhibitors in non-small-cell lung cancer.

Our group is also part of the clinical research effort at DFHCC, with a focus in non-small-cell lung cancer. We are part of the NIH/NCI-funded SPORE in Lung Cancer at DFHCC.

(co-investigators: Daniel G. Tenen, MD, Mark Huberman, MD and Susumu Kobayashi, MD, PhD)


 Bibliographic 
 selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Yasuda H, Park E, Yun CH, Sng NJ, Lucena-Araujo AR, Yeo WL, Huberman MS, Cohen DW, Nakayama S, Ishioka K, Yamaguchi N, Hanna M, Oxnard GR, Lathan CS, Moran T, Sequist LV, Chaft JE, Riely GJ, Arcila ME, Soo RA, Meyerson M, Eck MJ, Kobayashi SS, Costa DB. Structural, Biochemical, and Clinical Characterization of Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations in Lung Cancer. Sci Transl Med. 2013 Dec 18; 5(216):216ra177.
    View in: PubMed
  2. Oxnard GR, Nguyen KS, Costa DB. Germline mutations in driver oncogenes and inherited lung cancer risk independent of smoking history. J Natl Cancer Inst. 2014 Jan 1; 106(1):djt361.
    View in: PubMed
  3. Folch E, Yamaguchi N, Vanderlaan PA, Kocher ON, Boucher DH, Goldstein MA, Huberman MS, Kent MS, Gangadharan SP, Costa DB, Majid A. Adequacy of lymph node transbronchial needle aspirates using convex probe endobronchial ultrasound for multiple tumor genotyping techniques in non-small-cell lung cancer. J Thorac Oncol. 2013 Nov; 8(11):1438-44.
    View in: PubMed
  4. Brunner AM, Costa DB, Heist RS, Garcia E, Lindeman NI, Sholl LM, Oxnard GR, Johnson BE, Hammerman PS. Treatment-Related Toxicities in a Phase II Trial of Dasatinib in Patients with Squamous Cell Carcinoma of the Lung. J Thorac Oncol. 2013 Nov; 8(11):1434-7.
    View in: PubMed
  5. Yamaguchi N, Lucena-Araujo AR, Nakayama S, de Figueiredo-Pontes LL, Gonzalez DA, Yasuda H, Kobayashi S, Costa DB. Dual ALK and EGFR inhibition targets a mechanism of acquired resistance to the tyrosine kinase inhibitor crizotinib in ALK rearranged lung cancer. Lung Cancer. 2014 Jan; 83(1):37-43.
    View in: PubMed
  6. Yamaguchi N, Vanderlaan PA, Folch E, Boucher DH, Canepa HM, Kent MS, Gangadharan SP, Majid A, Kocher ON, Goldstein MA, Huberman MS, Costa DB. Smoking status and self-reported race affect the frequency of clinically relevant oncogenic alterations in non-small-cell lung cancers at a United States-based academic medical practice. Lung Cancer. 2013 Oct; 82(1):31-7.
    View in: PubMed
  7. Costa DB. Identification of somatic genomic alterations in circulating tumors cells: another step forward in non-small-cell lung cancer? J Clin Oncol. 2013 Jun 20; 31(18):2236-9.
    View in: PubMed
  8. Srivastava N, Vanderlaan PA, Kelly CP, Costa DB. Esophagitis: A Novel Adverse Event of Crizotinib in a Patient with ALK-Positive Non-Small-Cell Lung Cancer. J Thorac Oncol. 2013 Mar; 8(3):e23-4.
    View in: PubMed
  9. Klempner SJ, Costa DB, Wu PA, Ariyabuddhiphongs KD. Safety of cupping during bevacizumab therapy. J Altern Complement Med. 2013 Aug; 19(8):729-31.
    View in: PubMed
  10. Kobayashi S, Canepa HM, Bailey AS, Nakayama S, Yamaguchi N, Goldstein MA, Huberman MS, Costa DB. Compound EGFR Mutations and Response to EGFR Tyrosine Kinase Inhibitors. J Thorac Oncol. 2013 Jan; 8(1):45-51.
    View in: PubMed
  11. Gaughan EM, Cryer SK, Yeap BY, Jackman DM, Costa DB. Family history of lung cancer in never smokers with non-small-cell lung cancer and its association with tumors harboring EGFR mutations. Lung Cancer. 2013 Mar; 79(3):193-7.
    View in: PubMed
  12. Ackerman A, Goldstein MA, Kobayashi S, Costa DB. EGFR delE709_T710insD: a rare but potentially EGFR inhibitor responsive mutation in non-small-cell lung cancer. J Thorac Oncol. 2012 Oct; 7(10):e19-20.
    View in: PubMed
  13. Camidge DR, Bang YJ, Kwak EL, Iafrate AJ, Varella-Garcia M, Fox SB, Riely GJ, Solomon B, Ou SH, Kim DW, Salgia R, Fidias P, Engelman JA, Gandhi L, Jänne PA, Costa DB, Shapiro GI, Lorusso P, Ruffner K, Stephenson P, Tang Y, Wilner K, Clark JW, Shaw AT. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol. 2012 Oct; 13(10):1011-9.
    View in: PubMed
  14. Shaw AT, Varghese AM, Solomon BJ, Costa DB, Novello S, Mino-Kenudson M, Awad MM, Engelman JA, Riely GJ, Monica V, Yeap BY, Scagliotti GV. Pemetrexed-based chemotherapy in patients with advanced, ALK-positive non-small cell lung cancer. Ann Oncol. 2013 Jan; 24(1):59-66.
    View in: PubMed
  15. Yasuda H, de Figueiredo-Pontes LL, Kobayashi S, Costa DB. Preclinical rationale for use of the clinically available multitargeted tyrosine kinase inhibitor crizotinib in ROS1-translocated lung cancer. J Thorac Oncol. 2012 Jul; 7(7):1086-90.
    View in: PubMed
  16. Heon S, Yeap BY, Lindeman NI, Joshi VA, Butaney M, Britt GJ, Costa DB, Rabin MS, Jackman DM, Johnson BE. The impact of initial gefitinib or erlotinib versus chemotherapy on central nervous system progression in advanced non-small cell lung cancer with EGFR mutations. Clin Cancer Res. 2012 Aug 15; 18(16):4406-14.
    View in: PubMed
  17. Chen Z, Cheng K, Walton Z, Wang Y, Ebi H, Shimamura T, Liu Y, Tupper T, Ouyang J, Li J, Gao P, Woo MS, Xu C, Yanagita M, Altabef A, Wang S, Lee C, Nakada Y, Peña CG, Sun Y, Franchetti Y, Yao C, Saur A, Cameron MD, Nishino M, Hayes DN, Wilkerson MD, Roberts PJ, Lee CB, Bardeesy N, Butaney M, Chirieac LR, Costa DB, Jackman D, Sharpless NE, Castrillon DH, Demetri GD, Jänne PA, Pandolfi PP, Cantley LC, Kung AL, Engelman JA, Wong KK. A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response. Nature. 2012 Mar 29; 483(7391):613-7.
    View in: PubMed
  18. Costa DB, Kobayashi S. Acquired resistance to the ALK inhibitor crizotinib in the absence of an ALK mutation. J Thorac Oncol. 2012 Mar; 7(3):623-5.
    View in: PubMed
  19. Basseres DS, D'Alò F, Yeap BY, Löwenberg EC, Gonzalez DA, Yasuda H, Dayaram T, Kocher ON, Godleski JJ, Richards WG, Meyerson M, Kobayashi S, Tenen DG, Halmos B, Costa DB. Frequent downregulation of the transcription factor Foxa2 in lung cancer through epigenetic silencing. Lung Cancer. 2012 Jul; 77(1):31-7.
    View in: PubMed
  20. Nguyen KS, Sanford RA, Huberman MS, Goldstein MA, McDonald DM, Farquhar M, Gangadharan SP, Kent MS, Michaud G, Majid A, Berman SM, Aronovitz JA, Nedea EA, Boiselle PM, Cohen DW, Kobayashi S, Costa DB. Patterns of care for non-small-cell lung cancer at an academic institution affiliated with a national cancer institute-designated cancer center. J Oncol Pract. 2012 Jan; 8(1):57-62.
    View in: PubMed
  21. Costa DB. More than just an oncogene translocation and a kinase inhibitor: Kevin's story. J Clin Oncol. 2012 Jan 1; 30(1):110-2.
    View in: PubMed
  22. Shaw AT, Yeap BY, Solomon BJ, Riely GJ, Gainor J, Engelman JA, Shapiro GI, Costa DB, Ou SH, Butaney M, Salgia R, Maki RG, Varella-Garcia M, Doebele RC, Bang YJ, Kulig K, Selaru P, Tang Y, Wilner KD, Kwak EL, Clark JW, Iafrate AJ, Camidge DR. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol. 2011 Oct; 12(11):1004-12.
    View in: PubMed
  23. Klempner SJ, Cohen DW, Costa DB. ALK translocation in non-small cell lung cancer with adenocarcinoma and squamous cell carcinoma markers. J Thorac Oncol. 2011 Aug; 6(8):1439-40.
    View in: PubMed
  24. Yasuda H, Kobayashi S, Costa DB. EGFR exon 20 insertion mutations in non-small-cell lung cancer: preclinical data and clinical implications. Lancet Oncol. 2012 Jan; 13(1):e23-31.
    View in: PubMed
  25. Sequist LV, von Pawel J, Garmey EG, Akerley WL, Brugger W, Ferrari D, Chen Y, Costa DB, Gerber DE, Orlov S, Ramlau R, Arthur S, Gorbachevsky I, Schwartz B, Schiller JH. Randomized phase II study of erlotinib plus tivantinib versus erlotinib plus placebo in previously treated non-small-cell lung cancer. J Clin Oncol. 2011 Aug 20; 29(24):3307-15.
    View in: PubMed
  26. Britt GJ, Gaughan EM, Nguyen KS, Warner JL, Goldstein MA, Huberman MS, Costa DB. Case series of treatment approaches in fit nonagenarians with stage IV non-small-cell lung cancer. J Thorac Dis. 2011 Jun; 3(2):141-3.
    View in: PubMed
  27. Gaughan EM, Costa DB. Genotype-driven therapies for non-small cell lung cancer: focus on EGFR, KRAS and ALK gene abnormalities. Ther Adv Med Oncol. 2011 May; 3(3):113-25.
    View in: PubMed
  28. Costa DB, Kobayashi S, Pandya SS, Yeo WL, Shen Z, Tan W, Wilner KD. CSF concentration of the anaplastic lymphoma kinase inhibitor crizotinib. J Clin Oncol. 2011 May 20; 29(15):e443-5.
    View in: PubMed
  29. Ortiz TM, Cohen DW, Kent MS, Jänne PA, Costa DB. KRAS mutation analysis helps to differentiate between pulmonary metastasis from colon adenocarcinoma in situ and primary lung adenocarcinoma. J Thorac Oncol. 2011 Jan; 6(1):220-2.
    View in: PubMed
  30. Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Jänne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, Iafrate AJ. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010 Oct 28; 363(18):1693-703.
    View in: PubMed
  31. Heon S, Yeap BY, Britt GJ, Costa DB, Rabin MS, Jackman DM, Johnson BE. Development of central nervous system metastases in patients with advanced non-small cell lung cancer and somatic EGFR mutations treated with gefitinib or erlotinib. Clin Cancer Res. 2010 Dec 1; 16(23):5873-82.
    View in: PubMed
  32. Cheng H, Xu X, Costa DB, Powell CA, Halmos B. Molecular testing in lung cancer: the time is now. Curr Oncol Rep. 2010 Sep; 12(5):335-48.
    View in: PubMed
  33. Costa DB, Kobayashi S, Yeo WL, Hamada A. Serum concentrations of Erlotinib at a dose of 25 mg daily. J Thorac Oncol. 2010 Aug; 5(8):1311-2.
    View in: PubMed
  34. 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. 2010 Jul; 5(7):1048-53.
    View in: PubMed
  35. Will B, Siddiqi T, Jordà MA, Shimamura T, Luptakova K, Staber PB, Costa DB, Steidl U, Tenen DG, Kobayashi S. Apoptosis induced by JAK2 inhibition is mediated by Bim and enhanced by the BH3 mimetic ABT-737 in JAK2 mutant human erythroid cells. Blood. 2010 Apr 8; 115(14):2901-9.
    View in: PubMed
  36. Shaw AT, Yeap BY, Mino-Kenudson M, Digumarthy SR, Costa DB, Heist RS, Solomon B, Stubbs H, Admane S, McDermott U, Settleman J, Kobayashi S, Mark EJ, Rodig SJ, Chirieac LR, Kwak EL, Lynch TJ, Iafrate AJ. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol. 2009 Sep 10; 27(26):4247-53.
    View in: PubMed
  37. Honma HN, De Capitani EM, Barbeiro Ade S, Costa DB, Morcillo A, Zambon L. Polymorphism of the CYP1A1*2A gene and susceptibility to lung cancer in a Brazilian population. J Bras Pneumol. 2009 Aug; 35(8):767-72.
    View in: PubMed
  38. Nguyen KS, Kobayashi S, Costa DB. Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancers dependent on the epidermal growth factor receptor pathway. Clin Lung Cancer. 2009 Jul; 10(4):281-9.
    View in: PubMed
  39. Costa DB, Kobayashi S. Gefitinib plus docetaxel in non-small-cell lung cancer. Lancet. 2009 Feb 14; 373(9663):541; author reply 542.
    View in: PubMed
  40. Costa DB, Nguyen KS, Cho BC, Sequist LV, Jackman DM, Riely GJ, Yeap BY, Halmos B, Kim JH, Jänne 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. 2008 Nov 1; 14(21):7060-7.
    View in: PubMed
  41. Germano CM, Castro Md, Rorato R, Costa DB, Antunes-Rodrigues J, Elias CF, Elias LL. Downregulation of melanocortin-4 receptor during refeeding and its modulation by adrenalectomy in rats. Horm Metab Res. 2008 Dec; 40(12):842-7.
    View in: PubMed
  42. Costa DB, Schumer ST, Tenen DG, Kobayashi S. Differential responses to erlotinib in epidermal growth factor receptor (EGFR)-mutated lung cancers with acquired resistance to gefitinib carrying the L747S or T790M secondary mutations. J Clin Oncol. 2008 Mar 1; 26(7):1182-4; author reply 1184-6.
    View in: PubMed
  43. Honma HN, De Capitani EM, Perroud MW, Barbeiro AS, Toro IF, Costa DB, Lima CS, Zambon L. Influence of p53 codon 72 exon 4, GSTM1, GSTT1 and GSTP1*B polymorphisms in lung cancer risk in a Brazilian population. Lung Cancer. 2008 Aug; 61(2):152-62.
    View in: PubMed
  44. Costa DB, Kobayashi S. Response of intracranial metastases to epidermal growth factor receptor tyrosine kinase inhibitors: it may all depend on EGFR mutations. J Clin Oncol. 2008 Feb 1; 26(4):686.
    View in: PubMed
  45. Costa DB, Kobayashi S, Schumer ST. Erlotinib-associated alopecia in a lung cancer patient. J Thorac Oncol. 2007 Dec; 2(12):1136-8.
    View in: PubMed
  46. Costa DB, Halmos B, Kumar A, Schumer ST, Huberman MS, Boggon TJ, Tenen DG, Kobayashi S. BIM mediates EGFR tyrosine kinase inhibitor-induced apoptosis in lung cancers with oncogenic EGFR mutations. PLoS Med. 2007 Oct; 4(10):1669-79; discussion 1680.
    View in: PubMed
  47. Steidl U, Steidl C, Ebralidze A, Chapuy B, Han HJ, Will B, Rosenbauer F, Becker A, Wagner K, Koschmieder S, Kobayashi S, Costa DB, Schulz T, O'Brien KB, Verhaak RG, Delwel R, Haase D, Trümper L, Krauter J, Kohwi-Shigematsu T, Griesinger F, Tenen DG. A distal single nucleotide polymorphism alters long-range regulation of the PU.1 gene in acute myeloid leukemia. J Clin Invest. 2007 Sep; 117(9):2611-20.
    View in: PubMed
  48. Costa DB, Kobayashi S, Tenen DG, Huberman MS. Pooled analysis of the prospective trials of gefitinib monotherapy for EGFR-mutant non-small cell lung cancers. Lung Cancer. 2007 Oct; 58(1):95-103.
    View in: PubMed
  49. Costa DB. To re-treat or not with gefitinib/erlotinib: This is the question for tyrosine kinase inhibitor-responsive lung cancers that progress. Lung Cancer. 2007 Aug; 57(2):251-2.
    View in: PubMed
  50. Costa DB, Li S, Kocher O, Feins RH, Keller SM, Schiller JH, Johnson DH, Tenen DG, Halmos B. Immunohistochemical analysis of C/EBPalpha in non-small cell lung cancer reveals frequent down-regulation in stage II and IIIA tumors: a correlative study of E3590. Lung Cancer. 2007 Apr; 56(1):97-103.
    View in: PubMed
  51. Costa DB, Kobayashi S. Are exon 19 deletions and L858R EGFR mutations in non-small-cell lung cancer clinically different? Br J Cancer. 2007 Jan 29; 96(2):399; author reply 400.
    View in: PubMed
  52. Steidl U, Rosenbauer F, Verhaak RG, Gu X, Ebralidze A, Otu HH, Klippel S, Steidl C, Bruns I, Costa DB, Wagner K, Aivado M, Kobbe G, Valk PJ, Passegué E, Libermann TA, Delwel R, Tenen DG. Essential role of Jun family transcription factors in PU.1 knockdown-induced leukemic stem cells. Nat Genet. 2006 Nov; 38(11):1269-77.
    View in: PubMed
  53. Costa DB, Huberman MS. Improvement of type 2 diabetes in a lung cancer patient treated with Erlotinib. Diabetes Care. 2006 Jul; 29(7):1711.
    View in: PubMed
  54. Costa DB, Miksad RA, Buff MS, Wang Y, Dezube BJ. Case of fatal sickle cell intrahepatic cholestasis despite use of exchange transfusion in an African-American patient. J Natl Med Assoc. 2006 Jul; 98(7):1183-7.
    View in: PubMed
  55. Costa DB, Dayaram T, D'Alo F, Wouters BJ, Tenen DG, Meyerson M, Tsao MS, Halmos B. C/EBP alpha mutations in lung cancer. Lung Cancer. 2006 Aug; 53(2):253-4.
    View in: PubMed
  56. Costa DB, Schumer ST. Three-year survival in metastatic non-small cell lung cancer treated with gefitinib. Lung Cancer. 2006 Jul; 53(1):123-4.
    View in: PubMed
  57. Costa DB, Fisher CA, Miller KB, Pihan GA, Steensma DP, Gibbons RJ, Higgs DR. 5-Azacytidine treatment of the patient with ATMDS. Eur J Haematol. 2006; 76:453.
  58. Costa DB. Recurrent infections in multiple myeloma. Mayo Clin Proc. 2006 Apr; 81(4):567-8; author reply 568.
    View in: PubMed
  59. Costa DB, Fisher CA, Miller KB, Pihan GA, Steensma DP, Gibbons RJ, Higgs DR. A novel mutation in the last exon of ATRX in a patient with alpha-thalassemia myelodysplastic syndrome. Eur J Haematol. 2006 May; 76(5):432-5, 453.
    View in: PubMed
  60. Costa DB, Stuart KE, Inzucchi SE. Hyperglycemia and biliary tract adenocarcinoma. J Gastroenterol Hepatol. 2006 Feb; 21(2):484-5.
    View in: PubMed
  61. Costa DB, Parker JA, Schumer ST. Modern treatment of lung cancer: case 3. Non-metastatic bilateral F-18 fluorodeoxyglucose avid adrenal glands in non-small-cell lung cancer. J Clin Oncol. 2005 Oct 20; 23(30):7740-2.
    View in: PubMed
  62. Costa DB, Lozovatsky L, Gallagher PG, Forget BG. A novel splicing mutation of the alpha-spectrin gene in the original hereditary pyropoikilocytosis kindred. Blood. 2005 Dec 15; 106(13):4367-9.
    View in: PubMed
  63. Bonon SH, Menoni SM, Rossi CL, De Souza CA, Vigorito AC, Costa DB, Costa SC. Surveillance of cytomegalovirus infection in haematopoietic stem cell transplantation patients. J Infect. 2005 Feb; 50(2):130-7.
    View in: PubMed
  64. Costa DB, Shin B, Cooper DL. Pneumococcemia as the presenting feature of multiple myeloma. Am J Hematol. 2004 Nov; 77(3):277-81.
    View in: PubMed
  65. Costa DB, Chen AA, Marginean EC, Inzucchi SE. Diabetes mellitus as the presenting feature of extrahepatic cholangiocarcinoma in situ: case report and review of literature. Endocr Pract. 2004 Sep-Oct; 10(5):417-23.
    View in: PubMed
  66. Costa DB, Aguiar JF, Varanda WA. Diversity of ion channels in HCl secreting cells of Rana castebeiana. Annals of the VI Symposium of Scientific Initiation of the University of Sao Paulo (USP). 1998; 1:(abstract 9.16):142. .
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