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


dbcosta@bidmc.harvard.edu

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

Beth Israel Deaconess Medical Center

EDUCATIONAL TITLES

  • Professor, Medicine, Harvard Medical School
  • Medical Staff, Oncology, Beth Israel Deaconess Medical Center
  • Medical Director of the Cancer Clinical Trials Office, Medicine, Beth Israel Deaconess Medical Center
  • Thoracic Oncology Group Leader, Medicine, Beth Israel Deaconess Medical Center

DF/HCC PROGRAM AFFILIATION

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, ROS1, MET, BRAF, RET, ERBB2, NTRK, KRAS among others) to tyrosine kinase inhibitors in non-small-cell lung cancer.

Our group is also part of the clinical research effort at Dana-Farber/Harvard Cancer Center (DFHCC), with a focus in lung cancer, tumor genomic biomarkers and immune checkpoint inhibitors. We are supported by both federal and non-federal grants, and we are part of the NIH/NCI SPORE in Lung Cancer at DFHCC.

One of the main focuses of the DFHCC Lung Cancer Program, in conjunction with the Cancer Clinical Trials Office (CCTO) at Beth Israel Deaconess Medical Center (BIDMC), is to conduct clinical trials that will establish the future evidence-based strategies to manage local, locally advanced and advanced lung cancers.

(co-investigators at BIDMC: Susumu Kobayashi, MD, PhD, Daniel G. Tenen, MD, Sidharta P. Gangadharan, MD; Adnan Majid, MD; Paul A. VanderLaan, MD, PhD and Deepa Rangachari, MD)

(co-investigators at DFCI: Pasi A. Janne, MD, PhD; Michael Eck, MD, PhD; Matthew Meyerson, MD, PhD; David A. Barbie, MD and Mark Awad, MD, PhD)

(co-investigators at MGH: Lecia V. Sequist, MD, MPH; Zofia Piotrowska, MD and Justin Gainor, MD)

Publications from Harvard Catalyst Profiles

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  • Viray H, Piper-Vallillo AJ, Widick P, Academia E, Shea M, Rangachari D, VanderLaan PA, Kobayashi SS, Costa DB. A Real-World Study of Patient Characteristics and Clinical Outcomes in Mutated Lung Cancer Treated with First-Line Osimertinib: Expanding the FLAURA Trial Results into Routine Clinical Practice. Cancers (Basel) 2024. PubMed
  • Kobayashi IS, Shaffer W, Viray H, Rangachari D, VanderLaan PA, Kobayashi SS, Costa DB. The Impact of On-Target Resistance Mediated by EGFR-T790M or EGFR-C797S on EGFR Exon 20 Insertion Mutation Active Tyrosine Kinase Inhibitors. JTO Clin Res Rep 2024; 5:100614. PubMed
  • Burns L, Hsu CY, Whisenant JG, Marmarelis ME, Presley CJ, Reckamp KL, Khan H, Jo Fidler M, Bestvina CM, Brahmer J, Puri S, Patel JD, Halmos B, Hirsch FR, Liu SV, Costa DB, Goldberg SB, Feldman LE, Mamdani H, Puc M, Mansfield AS, Islam N, Scilla KA, Garassino MC, Horn L, Peters S, Wakelee HA, Charlot M, Tapan U. Disparities in outcomes between Black and White patients in North America with thoracic malignancies and COVID-19 infection (TERAVOLT). Lung Cancer 2023; 186:107423. PubMed
  • Le X, Nadler E, Costa DB, Heymach JV. EGFR Tyrosine Kinase Inhibitors for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Podcast. Target Oncol 2023; 18:807-817. PubMed
  • Sentana-Lledo D, Academia E, Viray H, Rangachari D, Kobayashi SS, VanderLaan PA, Costa DB. exon 20 insertion mutations and mutations in lung cancer: a narrative review on approved targeted therapies from oral kinase inhibitors to antibody-drug conjugates. Transl Lung Cancer Res 2023; 12:1590-1610. PubMed
  • Shaffer W, Kobayashi IS, Sentana-Lledo D, Sundararaman S, Lee MD, Rangachari D, VanderLaan PA, Kobayashi SS, Costa DB. EGFR exon 19 insertion EGFR-K745_E746insIPVAIK and others with rare XPVAIK amino-acid insertions: Preclinical and clinical characterization of the favorable therapeutic window to all classes of approved EGFR kinase inhibitors. Lung Cancer 2023; 181:107250. PubMed
  • Schoepflin ZR, Academia E, Osataphan SA, Rangachari D, Sharifi S, VanderLaan PA, Costa DB. Deletion Exons 2 to 19: Case Report of a Rare ALK Inhibitor-Responsive Lung Cancer Driver Oncogene. JTO Clin Res Rep 2023; 4:100489. PubMed
  • Shibahara D, Akanuma N, Kobayashi IS, Heo E, Ando M, Fujii M, Jiang F, Prin PN, Pan G, Wong KK, Costa DB, Bararia D, Tenen DG, Watanabe H, Kobayashi SS. TIP60 is required for tumorigenesis in non-small cell lung cancer. Cancer Sci 2023. PubMed
  • Sentana-Lledo D, Viray H, Piper-Vallillo AJ, Widick P, Rangachari D, Wilson JL, Gangadharan SP, Aronovitz JA, Berman SM, VanderLaan PA, Costa DB. Complete pathologic response to short-course neoadjuvant alectinib in mediastinal node positive (N2) ALK rearranged lung cancer. Lung Cancer 2022; 172:124-126. PubMed
  • Viray H, Rangachari D, Costa DB. Trastuzumab Deruxtecan in Non-Small-Cell Lung Cancer. N Engl J Med 2022; 386:1769-1770. PubMed
  • Piper-Vallillo AJ, Kobayashi SS, Costa DB. Differential Pattern of Resistance and Sensitivity to Different Classes of MET Inhibitors for -Amplified Tumors With -D1228X or -Y1230X Mutations. JTO Clin Res Rep 2021; 2:100133. PubMed
  • Vasconcelos PENS, Kobayashi IS, Kobayashi SS, Costa DB. Preclinical characterization of mobocertinib highlights the putative therapeutic window of this novel EGFR inhibitor to EGFR exon 20 insertion mutations. JTO Clin Res Rep 2021. PubMed
  • Riely GJ, Neal JW, Camidge DR, Spira AI, Piotrowska Z, Costa DB, Tsao AS, Patel JD, Gadgeel SM, Bazhenova L, Zhu VW, West HL, Mekhail T, Gentzler RD, Nguyen D, Vincent S, Zhang S, Lin J, Bunn V, Jin S, Li S, Janne PA. Activity and Safety of Mobocertinib (TAK-788) in Previously Treated Non-Small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations From a Phase 1/2 Trial. 2021. PubMed
  • Xu W, Piper-Vallillo AJ, Bindal P, Wischhusen J, Patel JM, Costa DB, Peters MLB. Time to SARS-CoV-2 clearance among patients with cancer and COVID-19. Cancer Med 2021. PubMed
  • Sehgal K, Gill RR, Widick P, Bindal P, McDonald DC, Shea M, Rangachari D, Costa DB. Association of Performance Status With Survival in Patients With Advanced Non-Small Cell Lung Cancer Treated With Pembrolizumab Monotherapy. JAMA Netw Open 2021; 4:e2037120. PubMed
  • Kobayashi IS, Viray H, Rangachari D, Kobayashi SS, Costa DB. EGFR-D770>GY and Other Rare EGFR Exon 20 Insertion Mutations with a G770 Equivalence Are Sensitive to Dacomitinib or Afatinib and Responsive to EGFR Exon 20 Insertion Mutant-Active Inhibitors in Preclinical Models and Clinical Scenarios. Cells 2021. PubMed
  • Neal JW, Costa DB, Muzikansky A, Shrager JB, Lanuti M, Huang J, Ramachandran KJ, Rangachari D, Huberman MS, Piotrowska Z, Kris MG, Azzoli CG, Sequist LV, Chaft JE. Randomized Phase II Study of 3 Months or 2 Years of Adjuvant Afatinib in Patients With Surgically Resected Stage I-III -Mutant Non-Small-Cell Lung Cancer. JCO Precis Oncol 2021; 5:325-332. PubMed
  • Piper-Vallillo AJ, Halbert BT, Rangachari D, Kobayashi SS, Costa DB. Acquired Resistance to Osimertinib Plus Savolitinib Is Mediated by -D1228 and -Y1230 Mutations in -Mutated -Amplified Lung Cancer. JTO Clin Res Rep 2020; 1:100071. PubMed
  • Sehgal K, Rangachari D, VanderLaan PA, Kobayashi SS, Costa DB. Clinical Benefit of Tyrosine Kinase Inhibitors in Advanced Lung Cancer with EGFR-G719A and Other Uncommon EGFR Mutations. Oncologist 2020. PubMed
  • Pertejo-Fernandez A, Ricciuti B, Hammond SP, Marty FM, Recondo G, Rangachari D, Costa DB, Awad MM. Safety and efficacy of immune checkpoint inhibitors in patients with non-small cell lung cancer and hepatitis B or hepatitis C infection. Lung Cancer 2020; 145:181-185. PubMed
  • Sehgal K, Bulumulle A, Brody H, Gill RR, Macherla S, Qilleri A, McDonald DC, Cherry CR, Shea M, Huberman MS, VanderLaan PA, Weiss GJ, Walker PR, Costa DB, Rangachari D. Association of Extended Dosing Intervals or Delays in Pembrolizumab-based Regimens With Survival Outcomes in Advanced Non-small-cell Lung Cancer. Clin Lung Cancer 2020. PubMed
  • Sehgal K, Varkaris A, Viray H, VanderLaan PA, Rangachari D, Costa DB. Small cell transformation of non-small cell lung cancer on immune checkpoint inhibitors: uncommon or under-recognized? J Immunother Cancer 2020. PubMed
  • Sehgal K, Piper-Vallillo AJ, Viray H, Khan AM, Rangachari D, Costa DB. Cases of ROS1-rearranged lung cancer: when to use crizotinib, entrectinib, lorlatinib, and beyond? 2020. PubMed
  • Cooper AJ, Kobayashi Y, Kim D, Clifford SE, Kravets S, Dahlberg SE, Chambers ES, Li J, Rangachari D, Nguyen T, Costa DB, Rabin MS, Wagle N, Sholl LM, Jänne PA, Oxnard GR. Identification of a RAS-activating Fusion in an Exceptional Responder to Sunitinib with Non-Small Cell Lung Cancer. Clin Cancer Res 2020. PubMed
  • Widick P, Gill RR, Mantia C, Costa DB, Rangachari D. Extensive-Stage Small-Cell Lung Cancer With Sustained Complete Response to Single-Agent Nivolumab and Immune-Related Dermatitis. Clin Lung Cancer 2020; 21:e6-e9. PubMed
  • Sehgal K, Costa DB, Rangachari D. Extended-Interval Dosing Strategy of Immune Checkpoint Inhibitors in Lung Cancer: Will it Outlast the COVID-19 Pandemic? 2020; 10:1193. PubMed
  • Piper AJ, Sehgal K, Costa DB, Rangachari D. Can PD-L1 tumor proportion score be used as the key to unlocking the KEYNOTE studies of pembrolizumab in advanced lung cancer? Transl Lung Cancer Res 2019; 8:715-722. PubMed
  • Udagawa H, Hasako S, Ohashi A, Fujioka R, Hakozaki Y, Shibuya M, Abe N, Komori T, Haruma T, Terasaka M, Fujita R, Hashimoto A, Funabashi K, Yasuda H, Miyadera K, Goto K, Costa DB, Kobayashi SS. TAS6417/CLN-081 Is a Pan-Mutation-Selective EGFR Tyrosine Kinase Inhibitor with a Broad Spectrum of Preclinical Activity against Clinically Relevant Mutations. Mol Cancer Res 2019. PubMed
  • Awad MM, Leonardi GC, Kravets S, Dahlberg SE, Drilon A, Noonan SA, Camidge DR, Ou SI, Costa DB, Gadgeel SM, Steuer CE, Forde PM, Zhu VW, Fukuda Y, Clark JW, Jänne PA, Mok T, Sholl LM, Heist RS. Impact of MET inhibitors on survival among patients with non-small cell lung cancer harboring MET exon 14 mutations: a retrospective analysis. Lung Cancer 2019; 133:96-102. PubMed
  • Rangachari D, Costa DB. From Hope to Reality: Durable Overall Survival With Immune Checkpoint Inhibitors for Advanced Lung Cancer. J Clin Oncol 2019. PubMed
  • Zhang WC, Wells JM, Chow KH, Huang H, Yuan M, Saxena T, Melnick MA, Politi K, Asara JM, Costa DB, Bult CJ, Slack FJ. miR-147b-mediated TCA cycle dysfunction and pseudohypoxia initiate drug tolerance to EGFR inhibitors in lung adenocarcinoma. Nat Metab 2019; 1:460-474. PubMed
  • Varkaris A, Sehgal K, Rangachari D, Costa DB. Complete and Sustained Response of Brain Metastases to Programmed Death 1 Antibody Monotherapy in Treatment-naive Programmed Death Ligand 1-Positive Lung Cancer. J Thorac Oncol 2019; 14:e34-e36. PubMed
  • Pennell NA, Neal JW, Chaft JE, Azzoli CG, Jänne PA, Govindan R, Evans TL, Costa DB, Wakelee HA, Heist RS, Shapiro MA, Muzikansky A, Murthy S, Lanuti M, Rusch VW, Kris MG, Sequist LV. SELECT: A Phase II Trial of Adjuvant Erlotinib in Patients With Resected Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer. J Clin Oncol 2018. PubMed
  • Jorge SE, Lucena-Araujo AR, Yasuda H, Piotrowska Z, Oxnard GR, Rangachari D, Huberman MS, Sequist LV, Kobayashi SS, Costa DB. EGFR Exon 20 Insertion Mutations Display Sensitivity to Hsp90 Inhibition in Preclinical Models and Lung Adenocarcinomas. Clin Cancer Res 2018. PubMed
  • Bahcall M, Awad MM, Sholl LM, Wilson FH, Xu M, Wang S, Palakurthi S, Choi J, Ivanova EV, Leonardi GC, Ulrich BC, Paweletz CP, Kirschmeier PT, Watanabe M, Baba H, Nishino M, Nagy RJ, Lanman RB, Capelletti M, Chambers ES, Redig AJ, VanderLaan PA, Costa DB, Imamura Y, Jänne PA. Amplification of Wild-type Imparts Resistance to Crizotinib in Exon 14 Mutant Non-Small Cell Lung Cancer. Clin Cancer Res 2018. PubMed
  • Oxnard GR, Hu Y, Mileham KF, Husain H, Costa DB, Tracy P, Feeney N, Sholl LM, Dahlberg SE, Redig AJ, Kwiatkowski DJ, Rabin MS, Paweletz CP, Thress KS, Jänne PA. Assessment of Resistance Mechanisms and Clinical Implications in Patients With EGFR T790M-Positive Lung Cancer and Acquired Resistance to Osimertinib. JAMA Oncol 2018. PubMed
  • Sehgal K, Patell R, Rangachari D, Costa DB. Targeting rearrangements in non-small cell lung cancer with crizotinib and other kinase inhibitors. Transl Cancer Res 2018; 7:S779-S786. PubMed
  • Sehgal K, Peters MLB, VanderLaan PA, Rangachari D, Kobayashi SS, Costa DB. Activity of Brigatinib in the Setting of Alectinib Resistance Mediated by ALK I1171S in ALK-Rearranged Lung Cancer. J Thorac Oncol 2018. PubMed
  • Ostios-Garcia L, Faig J, Leonardi GC, Adeni AE, Subegdjo SJ, Lydon CA, Rangachari D, Huberman MS, Sehgal K, Shea M, VanderLaan PA, Cheng MP, Marty FM, Hammond SP, Costa DB, Awad MM. Safety and Efficacy of PD-1 Inhibitors Among HIV-Positive Patients With Non-Small Cell Lung Cancer. J Thorac Oncol 2018; 13:1037-1042. PubMed
  • VanderLaan PA, Chen Y, DiStasio M, Rangachari D, Costa DB, Heher YK. Molecular Testing Turnaround Time in Non-Small-Cell Lung Cancer: Monitoring a Moving Target. Clin Lung Cancer 2018. PubMed
  • Rangachari D, VanderLaan PA, Costa DB. Updated Correlation of 22C3-PD-L1 ≥50% Expression with Driver Oncogene Mutations and Response to Pembrolizumab in the Kinase Inhibitor-Resistant Setting. J Thorac Oncol 2018; 13:e81-e83. PubMed
  • VanderLaan PA, Rangachari D, Majid A, Parikh MS, Gangadharan SP, Kent MS, McDonald DC, Huberman MS, Kobayashi SS, Costa DB. Tumor biomarker testing in non-small-cell lung cancer: A decade of change. Lung Cancer 2018; 116:90-95. PubMed
  • VanderLaan PA, Rangachari D, Costa DB. Lung Cancer with a High Tumor Mutational Burden. N Engl J Med 2018; 379:1093. PubMed
  • Shea M, Rangachari D, Hallowell RW, Hollie NI, Costa DB, VanderLaan PA. Radiologic and autopsy findings in a case of fatal immune checkpoint inhibitor-associated pneumonitis. Cancer Treat Res Commun 2018; 15:17-20. PubMed
  • Heidinger BH, Anderson KR, Nemec U, Costa DB, Gangadharan SP, VanderLaan PA, Bankier AA. Morphologic characteristics of pulmonary adenocarcinomas manifesting as pure ground-glass nodules on CT. J Thorac Dis 2017; 9:E1148-E1150. PubMed
  • Le X, Rangachari D, Costa DB. Moving more potent and less toxic options to the frontline in the management of advanced lung cancer. J Thorac Dis 2017; 9:2812-2818. PubMed
  • Carney BJ, Rangachari D, VanderLaan PA, Gowen K, Schrock AB, Ali SM, Costa DB. De novo ERBB2 amplification causing intrinsic resistance to erlotinib in EGFR-L858R mutated TKI-naïve lung adenocarcinoma. Lung Cancer 2017. PubMed
  • Costa DB. Ascending role of next-generation ALK inhibitors. Lancet Oncol. 2017; 18:837-839. PubMed
  • Heidinger BH, Nemec U, Anderson KR, Costa DB, Gangadharan SP, VanderLaan PA, Bankier AA. "Rounding" the Size of Pulmonary Nodules: Impact of Rounding Methods on Nodule Management, as Defined by the 2017 Fleischner Society Guidelines. Acad Radiol 2017. PubMed
  • Soo RA, Stone EC, Cummings KM, Jett JR, Field JK, Groen HJ, Mulshine JL, Yatabe Y, Bubendorf L, Dacic S, Rami-Porta R, Detterbeck FC, Lim E, Asamura H, Donington J, Wakelee HA, Wu YL, Higgins K, Senan S, Solomon B, Kim DW, Johnson M, Yang JC, Sequist LV, Shaw AT, Ahn MJ, Costa DB, Patel JD, Horn L, Gettinger S, Peters S, Wynes MW, Faivre-Finn C, Rudin CM, Tsao A, Baas P, Kelly RJ, Leighl NB, Scagliotti GV, Gandara DR, Hirsch FR, Spigel DR. Scientific Advances in Thoracic Oncology 2016. J Thorac Oncol 2017. PubMed
  • Peters ML, Costa DB, Rangachari D. Compound Uncommon EGFR Mutations in a Patient with Advanced NSCLC and Durable Response to Sequential EGFR Targeted Therapies. J Thorac Oncol 2017; 12:e35-e36. PubMed
  • Rangachari D, Costa DB. Moving the mountain in advanced non-small-cell lung cancer: evolving immunotherapies for a dire disease. Transl Cancer Res 2017; 6:S151-S157. PubMed
  • Yanagita M, Redig AJ, Paweletz CP, Dahlberg SE, O'Connell A, Feeney N, Taibi M, Boucher D, Oxnard GR, Johnson BE, Costa DB, Jackman DM, Jänne PA. A Prospective Evaluation of Circulating Tumor Cells and Cell-Free DNA in EGFR-Mutant Non-Small Cell Lung Cancer Patients Treated with Erlotinib on a Phase II Trial. Clin Cancer Res 2016. PubMed
  • Costa DB. Resistance to ALK inhibitors: Pharmacokinetics, mutations or bypass signaling? Cell Cycle 2016. PubMed
  • Lucena-Araujo AR, Moran JP, VanderLaan PA, Dias-Santagata D, Folch E, Majid A, Kent MS, Gangadharan SP, Rangachari D, Huberman MS, Kobayashi SS, Costa DB. De novo ALK kinase domain mutations are uncommon in kinase inhibitor-naïve ALK rearranged lung cancers. Lung Cancer 2016; 99:17-22. PubMed
  • Redig AJ, Costa DB, Taibi M, Boucher D, Johnson BE, Jänne PA, Jackman DM. Prospective Study of Repeated Biopsy Feasibility and Acquired Resistance at Disease Progression in Patients With Advanced EGFR Mutant Lung Cancer Treated With Erlotinib in a Phase 2 Trial. JAMA Oncol 2016. PubMed
  • Sheikine Y, Rangachari D, McDonald DC, Huberman MS, Folch ES, VanderLaan PA, Costa DB. EGFR Testing in Advanced Non-Small-Cell Lung Cancer, A Mini-Review. Clin Lung Cancer 2016. PubMed
  • Costa DB. Kinase inhibitor-responsive genotypes in EGFR mutated lung adenocarcinomas: moving past common point mutations or indels into uncommon kinase domain duplications and rearrangements. Transl Lung Cancer Res 2016; 5:331-7. PubMed
  • Gao X, Le X, Costa DB. The safety and efficacy of osimertinib for the treatment of EGFR T790M mutation positive non-small-cell lung cancer. Expert Rev Anticancer Ther 2016; 16:383-90. PubMed
  • Gao X, VanderLaan PA, Bailey AS, Costa DB. Comprehensive Genomic Profiling Differentiates Metachronous Primary Small-Cell Lung Cancer From Late Recurrence. Clin Lung Cancer 2016. PubMed
  • Solomon BJ, Cappuzzo F, Felip E, Blackhall FH, Costa DB, Kim DW, Nakagawa K, Wu YL, Mekhail T, Paolini J, Tursi J, Usari T, Wilner KD, Selaru P, Mok TS. Intracranial Efficacy of Crizotinib Versus Chemotherapy in Patients With Advanced ALK-Positive Non-Small-Cell Lung Cancer: Results From PROFILE 1014. J Clin Oncol 2016. PubMed
  • Nemeth Z, Csizmadia E, Vikstrom L, Li M, Bisht K, Feizi A, Otterbein S, Zuckerbraun B, Costa DB, Pandolfi PP, Fillinger J, Döme B, Otterbein LE, Wegiel B. Alterations of tumor microenvironment by carbon monoxide impedes lung cancer growth. 2016. PubMed
  • Costa DB. ALK inhibitors: plateauing systemic and intracranial activity? Lancet Oncol. 2016. PubMed
  • Costa DB, Jorge SE, Moran JP, Freed JA, Zerillo JA, Huberman MS, Kobayashi SS. Pulse Afatinib for ERBB2 Exon 20 Insertion-Mutated Lung Adenocarcinomas. J Thorac Oncol 2016. PubMed
  • Shea M, Huberman MS, Costa DB. Lazarus-Type Response to Crizotinib in a Patient with Poor Performance Status and Advanced MET Exon 14 Skipping Mutation-Positive Lung Adenocarcinoma. J Thorac Oncol 2016. PubMed
  • Koyama S, Akbay EA, Li YY, Herter-Sprie GS, Buczkowski KA, Richards WG, Gandhi L, Redig AJ, Rodig SJ, Asahina H, Jones RE, Kulkarni MM, Kuraguchi M, Palakurthi S, Fecci PE, Johnson BE, Janne PA, Engelman JA, Gangadharan SP, Costa DB, Freeman GJ, Bueno R, Hodi FS, Dranoff G, Wong KK, Hammerman PS. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun 2016; 7:10501. PubMed
  • Costa DB, Kobayashi SS. Whacking a mole-cule: clinical activity and mechanisms of resistance to third generation EGFR inhibitors in EGFR mutated lung cancers with EGFR-T790M. Transl Lung Cancer Res 2015; 4:809-15. PubMed
  • Jorge SE, Schulman S, Freed JA, VanderLaan PA, Rangachari D, Kobayashi SS, Huberman MS, Costa DB. Responses to the multitargeted MET/ALK/ROS1 inhibitor crizotinib and co-occurring mutations in lung adenocarcinomas with MET amplification or MET exon 14 skipping mutation. Lung Cancer 2015; 90:369-74. PubMed
  • Shea M, Costa DB, Rangachari D. Management of advanced non-small cell lung cancers with known mutations or rearrangements: latest evidence and treatment approaches. Ther Adv Respir Dis 2015. PubMed
  • Hirano T, Yasuda H, Tani T, Hamamoto J, Oashi A, Ishioka K, Arai D, Nukaga S, Miyawaki M, Kawada I, Naoki K, Costa DB, Kobayashi SS, Betsuyaku T, Soejima K. In vitro modeling to determine mutation specificity of EGFR tyrosine kinase inhibitors against clinically relevant EGFR mutants in non-small-cell lung cancer. 2015; 6:38789-803. PubMed
  • Farago AF, Le LP, Zheng Z, Muzikansky A, Drilon A, Patel M, Bauer TM, Liu SV, Ou SI, Jackman D, Costa DB, Multani PS, Li GG, Hornby Z, Chow-Maneval E, Luo D, Lim JE, Iafrate AJ, Shaw AT. Durable Clinical Response to Entrectinib in NTRK1-Rearranged Non-Small Cell Lung Cancer. J Thorac Oncol 2015. PubMed
  • Le X, Freed JA, VanderLaan PA, Huberman MS, Rangachari D, Jorge SE, Lucena-Araujo AR, Kobayashi SS, Balasubramanian S, He J, Chudnovsky 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
  • Klempner SJ, 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
  • 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
  • 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
  • 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
  • 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 β is dispensable for development of lung adenocarcinoma. PLoS ONE 2015; 10:e0120647. 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
  • Costa DB. Clinical development and approval of second generation ALK inhibitors for ALK rearranged lung cancer. Transl Lung Cancer Res 2014; 3:373-5. 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
  • 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
  • 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. β-catenin contributes to lung tumor development induced by EGFR mutations. Cancer Res 2014; 74:5891-902. 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
  • 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
  • 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
  • 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
  • Klempner SJ, Costa DB, Wu PA, Ariyabuddhiphongs KD. Safety of cupping during bevacizumab therapy. J Altern Complement Med 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
  • 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
  • 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
  • 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; 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 2011; 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, 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
  • 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
  • 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, 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; 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, 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, 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, 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
  • Torous VF, Rangachari D, Gallant BP, Shea M, Costa DB, VanderLaan PA. PD-L1 testing using the clone 22C3 pharmDx kit for selection of patients with non-small cell lung cancer to receive immune checkpoint inhibitor therapy: are cytology cell blocks a viable option? J Am Soc Cytopathol ; 7:133-141. PubMed
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