Photo of Daniel B. Costa,  M.D., Ph.D, M.MSc.

Daniel B. Costa, M.D., Ph.D, M.MSc.

Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center
Phone: (617) 667-9236
Fax: (617) 975-5665

Daniel B. Costa, M.D., Ph.D, M.MSc.

Beth Israel Deaconess Medical Center


  • Associate Professor, Medicine, Harvard Medical School
  • Medical Staff, Hematology/Oncology, Beth Israel Deaconess Medical Center



  • Member, Center Scientific Council

Research Abstract

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, RET among others) 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 at BIDMC: Susumu Kobayashi, MD, PhD, Daniel G. Tenen, MD; Mark Huberman, MD and Deepa Rangachari, MD)

(co-investigators at DFCI: Pasi Janne, MD, PhD; Geoffrey Oxnard, MD; David Jackman, MD; Michael Eck, MD, PhD; Peter Hammerman, MD, PhD; Matthew Meyerson, MD, PhD; Kwok-Kin Wong, MD, PhD; and Bruce Johnson, MD)

(co-investigators at MGH: Lecia V. Sequist, MD, MPH; Alice Shaw, MD, PhD and Jeffrey Engelman, MD, PhD)


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  • Klempner SJ, Ignatius Ou SH, Costa DB, VanderLaan PA, Sanford EM, Schrock A, Gay L, Ali SM, Miller VA. The Clinical Use of Genomic Profiling to Distinguish Intrapulmonary Metastases From Synchronous Primaries in Non-Small-Cell Lung Cancer: A Mini-Review. Clin Lung Cancer 2015. PubMed
  • Le X, Freed JA, VanderLaan PA, Huberman MS, Rangachari D, Jorge SE, Lucena-Araujo AR, Kobayashi SS, Balasubramanian S, He J, Chudnovksy Y, Miller VA, Ali SM, Costa DB. Detection of Crizotinib-Sensitive Lung Adenocarcinomas With MET, ALK, and ROS1 Genomic Alterations via Comprehensive Genomic Profiling. Clin Lung Cancer 2015. PubMed
  • Le X, Desai NV, Majid A, Karp RS, Huberman MS, Rangachari D, Kent MS, Gangadharan SP, Folch E, VanderLaan PA, Costa DB. De novo pulmonary small cell carcinomas and large cell neuroendocrine carcinomas harboring EGFR mutations: Lack of response to EGFR inhibitors. Lung Cancer 2015. PubMed
  • Rangachari D, Yamaguchi N, VanderLaan PA, Folch E, Mahadevan A, Floyd SR, Uhlmann EJ, Wong ET, Dahlberg SE, Huberman MS, Costa DB. Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers. Lung Cancer 2015. PubMed
  • Costa DB, Shaw AT, Ou SH, Solomon BJ, Riely GJ, Ahn MJ, Zhou C, Shreeve SM, Selaru P, Polli A, Schnell P, Wilner KD, Wiltshire R, Camidge DR, Crinò L. Clinical Experience With Crizotinib in Patients With Advanced ALK-Rearranged Non-Small-Cell Lung Cancer and Brain Metastases. J Clin Oncol 2015. PubMed
  • Niederst MJ, Sequist LV, Poirier JT, Mermel CH, Lockerman EL, Garcia AR, Katayama R, Costa C, Ross KN, Moran T, Howe E, Fulton LE, Mulvey HE, Bernardo LA, Mohamoud F, Miyoshi N, VanderLaan PA, Costa DB, Jänne PA, Borger DR, Ramaswamy S, Shioda T, Iafrate AJ, Getz G, Rudin CM, Mino-Kenudson M, Engelman JA. RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer. Nat Commun 2015; 6:6377. PubMed
  • Cai Y, Hirata A, Nakayama S, VanderLaan PA, Levantini E, Yamamoto M, Hirai H, Wong KK, Costa DB, Watanabe H, Kobayashi SS. CCAAT/Enhancer Binding Protein 硫 Is Dispensable for Development of Lung Adenocarcinoma. PLoS ONE 2015; 10:e0120647. PubMed
  • Costa DB. Clinical development and approval of second generation ALK inhibitors for ALK rearranged lung cancer. Transl Lung Cancer Res 2015; 3:373-5. PubMed
  • Nakayama S, Sng N, Carretero J, Welner R, Hayashi Y, Yamamoto M, Tan AJ, Yamaguchi N, Yasuda H, Li D, Soejima K, Soo RA, Costa DB, Wong KK, Kobayashi SS. 硫-Catenin Contributes to Lung Tumor Development Induced by EGFR Mutations. Cancer Res 2014; 74:5891-902. PubMed
  • Shaw AT, Ou SH, Bang YJ, Camidge DR, Solomon BJ, Salgia R, Riely GJ, Varella-Garcia M, Shapiro GI, Costa DB, Doebele RC, Le LP, Zheng Z, Tan W, Stephenson P, Shreeve SM, Tye LM, Christensen JG, Wilner KD, Clark JW, Iafrate AJ. Crizotinib in ROS1-Rearranged Non-Small-Cell Lung Cancer. N Engl J Med 2014. PubMed
  • Honma HN, Perroud MW, Leme MS, Barbeiro AS, Saad BA, Morcillo AM, Vassallo J, Costa DB, Zambon L. EGFR activating mutations and their association with response to platinum-doublet chemotherapy in Brazilian non-small cell lung cancer patients. Target Oncol 2014. PubMed
  • Vanderlaan PA, Yamaguchi N, Folch E, Boucher DH, Kent MS, Gangadharan SP, Majid A, Goldstein MA, Huberman MS, Kocher ON, Costa DB. Success and failure rates of tumor genotyping techniques in routine pathological samples with non-small-cell lung cancer. Lung Cancer 2014; 84:39-44. PubMed
  • de Figueiredo-Pontes LL, Wong DW, Tin VP, Chung LP, Yasuda H, Yamaguchi N, Nakayama S, Jänne PA, Wong MP, Kobayashi SS, Costa DB. Identification and characterization of ALK kinase splicing isoforms in non-small-cell lung cancer. J Thorac Oncol 2014; 9:248-53. PubMed
  • Oxnard GR, Nguyen KS, Costa DB. Germline mutations in driver oncogenes and inherited lung cancer risk independent of smoking history. Journal of the National Cancer Institute 2014; 106:djt361. PubMed
  • 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; 83:37-43. PubMed
  • Gerber DE, Gandhi L, Costa DB. Management and future directions in non-small cell lung cancer with known activating mutations. Am Soc Clin Oncol Educ Book 2014; 34:e353-65. PubMed
  • 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; 5:216ra177. PubMed
  • 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; 8:1434-7. PubMed
  • 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; 8:1438-44. PubMed
  • 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; 82:31-7. PubMed
  • Costa DB. Identification of Somatic Genomic Alterations in Circulating Tumors Cells: Another Step Forward in Non-Small-Cell Lung Cancer? J Clin Oncol 2013. PubMed
  • Costa DN, Bloch BN, Yao DF, Sanda MG, Ngo L, Genega EM, Pedrosa I, Dewolf WC, Rofsky NM. Diagnosis of relevant prostate cancer using supplementary cores from magnetic resonance imaging-prompted areas following multiple failed biopsies. Magn Reson Imaging 2013. PubMed
  • 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; 79:193-7. PubMed
  • 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; 8:e23-4. PubMed
  • Klempner SJ, Costa DB, Wu PA, Ariyabuddhiphongs KD. Safety of Cupping During Bevacizumab Therapy. J Altern Complement Med 2013. PubMed
  • 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 2012; 8:45-51. PubMed
  • Bloch BN, Genega EM, Costa DN, Pedrosa I, Smith MP, Kressel HY, Ngo L, Sanda MG, Dewolf WC, Rofsky NM. Prediction of prostate cancer extracapsular extension with high spatial resolution dynamic contrast-enhanced 3-T MRI. Eur Radiol 2012; 22:2201-10. PubMed
  • 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; 13:1011-9. PubMed
  • 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; 7:e19-20. PubMed
  • 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; 18:4406-14. PubMed
  • 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; 7:1086-90. PubMed
  • 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. PubMed
  • 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 2010; 6:220-2. PubMed
  • 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; 16:5873-82. PubMed
  • 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; 363:1693-703. PubMed
  • Cheng H, Xu X, Costa DB, Powell CA, Halmos B. Molecular testing in lung cancer: the time is now. Curr Oncol Rep 2010; 12:335-48. PubMed
  • Costa DB, Kobayashi S, Yeo WL, Hamada A. Serum concentrations of Erlotinib at a dose of 25 mg daily. J Thorac Oncol 2010; 5:1311-2. PubMed
  • 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; 5:1048-53. PubMed
  • Will B, Siddiqi T, Alberich Jordà M, 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; 115:2901-9. PubMed
  • 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; 27:4247-53. PubMed
  • 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; 10:281-9. PubMed
  • Costa DB,Kobayashi S. Gefitinib plus docetaxel in non-small-cell lung cancer. Lancet 2009; 373:541; author reply 542. PubMed
  • Costa DB,Nguyen KS,Cho BC,Sequist LV,Jackman DM,Riely GJ,Yeap BY,Halmos B,Kim JH,Janne 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; 14:7060-7. PubMed
  • Honma HN, De Capitani EM, Perroud MW Jr, 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; 61:152-62. PubMed
  • 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; 26:1182-4; author reply 1184-6. PubMed
  • 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; 26:686. PubMed
  • Costa DB, Kobayashi S, Schumer ST. Erlotinib-associated alopecia in a lung cancer patient. J Thorac Oncol 2007; 2:1136-8. PubMed
  • 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; 58:95-103. PubMed
  • 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; 4:1669-79; discussion 1680. PubMed
  • 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, Trumper 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; 117:2611-20. PubMed
  • 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; 57:251-2. PubMed
  • 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; 56:97-103. PubMed
  • Costa DB, Kobayashi S. Are exon 19 deletions and L858R EGFR mutations in non-small-cell lung cancer clinically different? Br J Cancer 2007; 96:399; author reply 400. PubMed
  • 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, Passegu. Essential role of Jun family transcription factors in PU.1 knockdown-induced leukemic stem cells. Nat Genet 2006; 38:1269-77. PubMed
  • Costa DB, Dayaram T, D'Alo F, Wouters BJ, Tenen DG, Meyerson M, Tsao MS, Halmos B. C/EBPalpha mutations in lung cancer. Lung Cancer 2006; 53:253-4. PubMed
  • 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; 98:1183-7. PubMed
  • Costa DB, Schumer ST. Three-year survival in metastatic non-small cell lung cancer treated with gefitinib. Lung Cancer 2006; 53:123-4. PubMed
  • Costa DB, Huberman MS. Improvement of type 2 diabetes in a lung cancer patient treated with Erlotinib. Diabetes Care 2006; 29:1711. PubMed
  • 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; 76:432-5, 453. PubMed
  • Costa DB. Recurrent infections in multiple myeloma. Mayo Clin Proc 2006; 81:567-8; author reply 568. PubMed
  • Costa DB, Stuart KE, Inzucchi SE. Hyperglycemia and biliary tract adenocarcinoma. J Gastroenterol Hepatol 2006; 21:484-5. PubMed