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New strategies to develop new medications for lung cancer and metastasis

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Abstract

With the advances in cancer and molecular biology and the rapid progress in genomics, significant progress has been made in the treatment of lung cancer in the past decade. Targeted therapies have been developed for nonsmall cell lung cancer (NSCLC), and significant improvement in survival has been achieved. There is still, however, no cure for advanced NSCLC. Resistance to initial therapy is universal, and the lethal outcome of metastatic disease still remains. Approaches to preventing metastases and overcoming resistance to therapy are necessary to ensure long-term survival of patients with advanced lung cancer.

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References

  1. http://www.cancer.gov/cancertopics/types/lung. Accessed Jan 22 2015.

  2. Sharma, S. V., Bell, D. W., Settleman, J., & Haber, D. A. (2007). Epidermal growth factor receptor mutations in lung cancer. Nature Reviews Cancer, 7(3), 169–181. doi:10.1038/nrc2088.

    Article  CAS  PubMed  Google Scholar 

  3. Marchetti, A., Martella, C., Felicioni, L., Barassi, F., Salvatore, S., Chella, A., et al. (2005). EGFR mutations in non-small-cell lung cancer: analysis of a large series of cases and development of a rapid and sensitive method for diagnostic screening with potential implications on pharmacologic treatment. Journal of Clinical Oncology, 23(4), 857–865. doi:10.1200/JCO.2005.08.043.

    Article  CAS  PubMed  Google Scholar 

  4. Shigematsu, H., Lin, L., Takahashi, T., Nomura, M., Suzuki, M., Wistuba, I. I., et al. (2005). Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. Journal of the National Cancer Institute, 97(5), 339–346. doi:10.1093/jnci/dji055.

    Article  CAS  PubMed  Google Scholar 

  5. Kosaka, T., Yatabe, Y., Endoh, H., Kuwano, H., Takahashi, T., & Mitsudomi, T. (2004). Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications. Cancer Research, 64(24), 8919–8923. doi:10.1158/0008-5472.CAN-04-2818.

    Article  CAS  PubMed  Google Scholar 

  6. Janne, P. A., Engelman, J. A., & Johnson, B. E. (2005). Epidermal growth factor receptor mutations in non-small-cell lung cancer: implications for treatment and tumor biology. Journal of Clinical Oncology, 23(14), 3227–3234. doi:10.1200/JCO.2005.09.985.

    Article  CAS  PubMed  Google Scholar 

  7. http://www.cancer.gov/cancertopics/druginfo/fda-erlotinib-hydrochloride (2013). Accessed Jan 21 2015.

  8. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm360574.htm (2013). Accessed Jan 21 2015.

  9. Riely, G. J., Politi, K. A., Miller, V. A., & Pao, W. (2006). Update on epidermal growth factor receptor mutations in non-small cell lung cancer. Clinical Cancer Research, 12(24), 7232–7241. doi:10.1158/1078-0432.CCR-06-0658.

    Article  CAS  PubMed  Google Scholar 

  10. Linardou, H., Dahabreh, I. J., Bafaloukos, D., Kosmidis, P., & Murray, S. (2009). Somatic EGFR mutations and efficacy of tyrosine kinase inhibitors in NSCLC. Nature Reviews. Clinical Oncology, 6(6), 352–366. doi:10.1038/nrclinonc.2009.62.

    Article  CAS  PubMed  Google Scholar 

  11. Stella, G. M., Luisetti, M., Inghilleri, S., Cemmi, F., Scabini, R., Zorzetto, M., et al. (2012). Targeting EGFR in non-small-cell lung cancer: lessons, experiences, strategies. Respiratory Medicine, 106(2), 173–183. doi:10.1016/j.rmed.2011.10.015.

    Article  PubMed  Google Scholar 

  12. Soda, M., Choi, Y. L., Enomoto, M., Takada, S., Yamashita, Y., Ishikawa, S., et al. (2007). Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature, 448(7153), 561–566. doi:10.1038/nature05945.

    Article  CAS  PubMed  Google Scholar 

  13. http://www.cancer.gov/cancertopics/druginfo/fda-crizotinib (2013). Accessed Jan 21 2015.

  14. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm395299.htm (2014) Accessed Jan 25, 2015.

  15. Bergethon, K., Shaw, A. T., Ou, S. H., Katayama, R., Lovly, C. M., McDonald, N. T., et al. (2012). ROS1 rearrangements define a unique molecular class of lung cancers. Journal of Clinical Oncology, 30(8), 863–870. doi:10.1200/JCO.2011.35.6345.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Takeuchi, K., Soda, M., Togashi, Y., Suzuki, R., Sakata, S., Hatano, S., et al. (2012). RET, ROS1 and ALK fusions in lung cancer. Nature Medicine, 18(3), 378–381. doi:10.1038/nm.2658.

    Article  CAS  PubMed  Google Scholar 

  17. Shaw, A. T., Camidge, D. R., Engelman, J. A., Solomon, B. J., Kwak, E. L., Clark, J. W., et al. (2012). Clinical activity of crizotinib in advanced non-small cell lung cancer (NSCLC) harboring ROS1 gene rearrangement. Journal of Clinical Oncology, 30(15_suppl), 7508.

    Google Scholar 

  18. Sandler, A., Gray, R., Perry, M. C., Brahmer, J., Schiller, J. H., Dowlati, A., et al. (2006). Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. New England Journal of Medicine, 355(24), 2542–2550. doi:10.1056/NEJMoa061884.

    Article  CAS  PubMed  Google Scholar 

  19. http://www.cancer.gov/cancertopics/druginfo/fda-bevacizumab - Anchor-NSCLC (2014). Accessed Jan 21 2015.

  20. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm426735.htm (2014). Accessed Jan 22 2015.

  21. Paez, J. G., Janne, P. A., Lee, J. C., Tracy, S., Greulich, H., Gabriel, S., et al. (2004). EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science, 304(5676), 1497–1500. doi:10.1126/science.1099314.

    Article  CAS  PubMed  Google Scholar 

  22. Eberhard, D. A., Johnson, B. E., Amler, L. C., Goddard, A. D., Heldens, S. L., Herbst, R. S., et al. (2005). Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. Journal of Clinical Oncology, 23(25), 5900–5909. doi:10.1200/JCO.2005.02.857.

    Article  CAS  PubMed  Google Scholar 

  23. Sakurada, A., Shepherd, F. A., & Tsao, M. S. (2006). Epidermal growth factor receptor tyrosine kinase inhibitors in lung cancer: impact of primary or secondary mutations. Clinical Lung Cancer, 7(Suppl 4), S138–144.

    Article  CAS  PubMed  Google Scholar 

  24. Rosell, R., Carcereny, E., Gervais, R., Vergnenegre, A., Massuti, B., Felip, E., et al. (2012). Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncology, 13(3), 239–246. doi:10.1016/S1470-2045(11)70393-X.

    Article  CAS  PubMed  Google Scholar 

  25. Fukuoka, M., Wu, Y. L., Thongprasert, S., Sunpaweravong, P., Leong, S. S., Sriuranpong, V., et al. (2011). Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). Journal of Clinical Oncology, 29(21), 2866–2874. doi:10.1200/JCO.2010.33.4235.

    Article  CAS  PubMed  Google Scholar 

  26. Mok, T. S., Wu, Y. L., Thongprasert, S., Yang, C. H., Chu, D. T., Saijo, N., et al. (2009). Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. New England Journal of Medicine, 361(10), 947–957. doi:10.1056/NEJMoa0810699.

    Article  CAS  PubMed  Google Scholar 

  27. Balak, M. N., Gong, Y., Riely, G. J., Somwar, R., Li, A. R., Zakowski, M. F., et al. (2006). Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clinical Cancer Research, 12(21), 6494–6501. doi:10.1158/1078-0432.CCR-06-1570.

    Article  CAS  PubMed  Google Scholar 

  28. Kobayashi, S., Boggon, T. J., Dayaram, T., Janne, P. A., Kocher, O., Meyerson, M., et al. (2005). EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. New England Journal of Medicine, 352(8), 786–792. doi:10.1056/NEJMoa044238.

    Article  CAS  PubMed  Google Scholar 

  29. Kosaka, T., Yatabe, Y., Endoh, H., Yoshida, K., Hida, T., Tsuboi, M., et al. (2006). Analysis of epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer and acquired resistance to gefitinib. Clinical Cancer Research, 12(19), 5764–5769. doi:10.1158/1078-0432.CCR-06-0714.

    Article  CAS  PubMed  Google Scholar 

  30. Godin-Heymann, N., Ulkus, L., Brannigan, B. W., McDermott, U., Lamb, J., Maheswaran, S., et al. (2008). The T790M "gatekeeper" mutation in EGFR mediates resistance to low concentrations of an irreversible EGFR inhibitor. Molecular Cancer Therapeutics, 7(4), 874–879. doi:10.1158/1535-7163.MCT-07-2387.

    Article  CAS  PubMed  Google Scholar 

  31. Ware, K. E., Hinz, T. K., Kleczko, E., Singleton, K. R., Marek, L. A., Helfrich, B. A., et al. (2013). A mechanism of resistance to gefitinib mediated by cellular reprogramming and the acquisition of an FGF2-FGFR1 autocrine growth loop. Oncogenesis, 2, e39. doi:10.1038/oncsis.2013.4.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Yun, C. H., Mengwasser, K. E., Toms, A. V., Woo, M. S., Greulich, H., Wong, K. K., et al. (2008). The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proceedings of the National Academy of Sciences of the United States of America, 105(6), 2070–2075. doi:10.1073/pnas.0709662105.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Kwak, E. L., Sordella, R., Bell, D. W., Godin-Heymann, N., Okimoto, R. A., Brannigan, B. W., et al. (2005). Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib. Proceedings of the National Academy of Sciences of the United States of America, 102(21), 7665–7670. doi:10.1073/pnas.0502860102.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Miller, V. A., Hirsh, V., Cadranel, J., Chen, Y. M., Park, K., Kim, S. W., et al. (2012). Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncology, 13(5), 528–538. doi:10.1016/S1470-2045(12)70087-6.

    Article  CAS  PubMed  Google Scholar 

  35. Reckamp, K. L., Giaccone, G., Camidge, D. R., Gadgeel, S. M., Khuri, F. R., Engelman, J. A., et al. (2014). A phase 2 trial of dacomitinib (PF-00299804), an oral, irreversible pan-HER (human epidermal growth factor receptor) inhibitor, in patients with advanced non-small cell lung cancer after failure of prior chemotherapy and erlotinib. Cancer, 120(8), 1145–1154. doi:10.1002/cncr.28561.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Tjin Tham Sjin, R., Lee, K., Walter, A. O., Dubrovskiy, A., Sheets, M., Martin, T. S., et al. (2014). In vitro and in vivo characterization of irreversible mutant-selective EGFR inhibitors that are wild-type sparing. Molecular Cancer Therapeutics, 13(6), 1468–1479. doi:10.1158/1535-7163.MCT-13-0966.

    Article  PubMed  Google Scholar 

  37. Walter, A. O., Sjin, R. T., Haringsma, H. J., Ohashi, K., Sun, J., Lee, K., et al. (2013). Discovery of a mutant-selective covalent inhibitor of EGFR that overcomes T790M-mediated resistance in NSCLC. Cancer Discovery, 3(12), 1404–1415. doi:10.1158/2159-8290.CD-13-0314.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Sequist, L. V., Soria J. C., Wakelee H. A., Camidge D. R.,Varga A, Solomon B. J. et al. (2014). First-inhuman evaluation of CO-1686, an irreversible, highly selective tyrosine kinase inhibitor of mutations of EGFR (activating and T790M). J Clin Oncol, 32(5 s), abstr 8010.

  39. https://clinicaltrials.gov/ct2/results?term=Rociletinib&Search=Search. Accessed Jan 25, 2015.

  40. Cross, D. A., Ashton, S. E., Ghiorghiu, S., Eberlein, C., Nebhan, C. A., Spitzler, P. J., et al. (2014). AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discovery, 4(9), 1046–1061. doi:10.1158/2159-8290.CD-14-0337.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Yang J., Kim. D., Planchard D., Ohe Y., Ramalingam S. S., Ahn M. et al. (2014). Updated safety and efficacy from a phase i study of azd9291 in patients (pts) with EGFR-TKI-resistant non-small cell lung cancer (NSCLC). Annals of Oncology, 25(4 s); 449PD

  42. Janne, P. A., Ramalingam S. S., Yang J., Ahn M.J., Kim D., Kim S. et al. (2014). Clinical activity of the mutant-selective EGFR inhibitor AZD9291 in patients (pts) with EGFR inhibitor–resistant non-small cell lung cancer (NSCLC). Journal of Clinical Oncology, 32(5 s), suppl; abstr 8009.

  43. https://clinicaltrials.gov/ct2/show/NCT02094261?term=AZD9291&rank=15 (2015). Accessed Jan 25, 2015.

  44. https://clinicaltrials.gov/ct2/show/NCT02296125 (2015). Accessed Jan 25, 2015.

  45. https://clinicaltrials.gov/ct2/show/NCT02151981?term=AZD9291&rank=12 (2015). Accessed Jan 25, 2015.

  46. https://clinicaltrials.gov/ct2/show/NCT02143466 (2015). Accessed Feb 10 2015.

  47. Sakagami, H., Konagai, S., Yamamoto, H., Tanaka, H., Matsuya, T., Mori, M., et al. (2014). ASP8273, a novel mutant-selective irreversible EGFR inhibitor, inhibits growth of non-small cell lung cancer (NSCLC) cells with EGFR activating and T790M resistance mutations. Cancer Research, 74(19 s), 1728. doi:10.1158/1538-7445.AM2014-1728.

  48. Murakami, H., Nokihara, H., Shimizu, T., Seto, T., Keating, A., Krivoshik, A. et al. (2014). Antitumor activity ofASP8273, an irreversible mutant selective EGFR-TKI, in NSCLC patients with tumors harboring EGFR activating mutations and T790M resistance mutation. 26th, European Journal of Cancer, 50(s 6), 168. doi:10.1016/S0959-8049(14)70730-0.

  49. https://clinicaltrials.gov/ct2/show/NCT02192697?term=ASP8273&rank=1 (2015). Accessed Jan 25, 2015.

  50. Lee, K. O., Cha, M. Y., Kim, M., Song, J. Y., Lee, J. H., Kim, Y. H., et al. (2014). Discovery of HM61713 as anorally available and mutant EGFR selective inhibitor. Cancer Research, 74(19 s):Abstract nr LB-100. doi:10.1158/1538-7445.AM2014-LB-100.

  51. Kim, D. W., Lee, D. H., Kang, J. H., Park, K., Han, J. Y., Lee, J. S., Jang, I. J., et al. (2014). Clinical activity and safety of HM61713, an EGFR-mutant selective inhibitor, in advanced non-small cell lung cancer (NSCLC) patients (pts) with EGFR mutations who had received EGFR tyrosine kinase inhibitors (TKIs). Journal of Clinical Oncology, 32(5 s), 8011.

    Google Scholar 

  52. Morris, S. W., Kirstein, M. N., Valentine, M. B., Dittmer, K. G., Shapiro, D. N., Saltman, D. L., et al. (1994). Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma. Science, 263(5151), 1281–1284.

    Article  CAS  PubMed  Google Scholar 

  53. Choi, Y. L., Takeuchi, K., Soda, M., Inamura, K., Togashi, Y., Hatano, S., et al. (2008). Identification of novel isoforms of the EML4-ALK transforming gene in non-small cell lung cancer. Cancer Research, 68(13), 4971–4976. doi:10.1158/0008-5472.CAN-07-6158.

    Article  CAS  PubMed  Google Scholar 

  54. Koivunen, J. P., Mermel, C., Zejnullahu, K., Murphy, C., Lifshits, E., Holmes, A. J., et al. (2008). EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clinical Cancer Research, 14(13), 4275–4283. doi:10.1158/1078-0432.CCR-08-0168.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Soda, M., Takada, S., Takeuchi, K., Choi, Y. L., Enomoto, M., Ueno, T., et al. (2008). A mouse model for EML4-ALK-positive lung cancer. Proceedings of the National Academy of Sciences of the United States of America, 105(50), 19893–19897. doi:10.1073/pnas.0805381105.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Ardini, E., & Galvani, A. (2012). ALK Inhibitors, a Pharmaceutical Perspective. Front Oncology, 2, 17. doi:10.3389/fonc.2012.00017.

    Article  Google Scholar 

  57. Kwak, E. L., Bang, Y. J., Camidge, D. R., Shaw, A. T., Solomon, B., Maki, R. G., et al. (2010). Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. New England Journal of Medicine, 363(18), 1693–1703. doi:10.1056/NEJMoa1006448.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Shaw, A. T., Kim, D. W., Nakagawa, K., Seto, T., Crino, L., Ahn, M. J., et al. (2013). Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. New England Journal of Medicine, 368(25), 2385–2394. doi:10.1056/NEJMoa1214886.

    Article  CAS  PubMed  Google Scholar 

  59. Maillet, D., Martel-Lafay, I., Arpin, D., & Perol, M. (2013). Ineffectiveness of crizotinib on brain metastases in two cases of lung adenocarcinoma with EML4-ALK rearrangement. Journal of Thoracic Oncology, 8(4), e30–31. doi:10.1097/JTO.0b013e318288dc2d.

    Article  PubMed  Google Scholar 

  60. Gainor, J. F., Ou, S. H., Logan, J., Borges, L. F., & Shaw, A. T. (2013). The central nervous system as a sanctuary site in ALK-positive non-small-cell lung cancer. Journal of Thoracic Oncology, 8(12), 1570–1573. doi:10.1097/JTO.0000000000000029.

    Article  CAS  PubMed  Google Scholar 

  61. Awad, M. M., & Shaw, A. T. (2014). ALK inhibitors in non-small cell lung cancer: crizotinib and beyond. Clinical Advances in Hematology and Oncology, 12(7), 429–439.

    PubMed Central  PubMed  Google Scholar 

  62. Sakamoto, H., Tsukaguchi, T., Hiroshima, S., Kodama, T., Kobayashi, T., Fukami, T. A., et al. (2011). CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell, 19(5), 679–690. doi:10.1016/j.ccr.2011.04.004.

    Article  CAS  PubMed  Google Scholar 

  63. Kodama, T., Tsukaguchi, T., Satoh, Y., Yoshida, M., Watanabe, Y., Kondoh, O., et al. (2014). Alectinib shows potent antitumor activity against RET-rearranged non-small cell lung cancer. Molecular Cancer Therapeutics, 13(12), 2910–2918. doi:10.1158/1535-7163.MCT-14-0274.

    Article  CAS  PubMed  Google Scholar 

  64. Gadgeel, S. M., Gandhi, L., Riely, G. J., Chiappori, A. A., West, H. L., Azada, M. C., et al. (2014). Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study. Lancet Oncology, 15(10), 1119–1128. doi:10.1016/S1470-2045(14)70362-6.

    Article  CAS  PubMed  Google Scholar 

  65. https://clinicaltrials.gov/ct2/show/NCT02075840?term=Alectinib&rank=3 Accessed Jan 25, 2015.

  66. Squillace, R. M., Anjum, R., Miller, D., Vodala, S., Moran, L., Wang, F., et al. (2014). AP26113 possesses pan-inhibitory activity versus crizotinib-resistant ALK mutants and oncogenic ROS1 fusions. Cancer Research, 73, 5655.

    Article  Google Scholar 

  67. Rivera, V. M., Wang, F., Anjum, R., Zhang, S., Squillace, R., Keats, J., et al. (2012). AP26113 is a dual ALK/EGFR inhibitor: Characterization against EGFR T790M in cell and mouse models of NSCLC. Cancer Research, 72, 1794.

    Article  Google Scholar 

  68. Zhang, S., Wang, F., Keats, J., Ning, Y., Wardwell, S. D., Moran, L., et al. (2010). AP26113, a potent ALKinhibitor, overcomes mutations in EML4-ALK that confer resistance to PF-02341066. Cancer Res, 70(8s):Abstract nr LB-298. doi:10.1158/1538-7445.AM10-LB-298.

  69. Gettinger, S. N., Bazhenova, L., Salgia, R., Langer, C. J., Gold, K. A., Rosell, R., et al. (2014). Updated efficacy and safety of the ALK inhibitor AP26113 in patients (pts) with advanced malignancies, including ALK+ non-small cell lung cancer (NSCLC). Journal of Clinical Oncology, 32(5s), abstr 8047.

  70. http://investor.ariad.com/phoenix.zhtml?c=118422&p=irol-newsArticle&id=1973346 Accessed Jan 25, 2015.

  71. https://clinicaltrials.gov/ct2/show/NCT02094573?term=AP26113&rank=1 Accessed Jan 25, 2015.

  72. Mori, M., Ueno, Y., Konagai, S., Fushiki, H., Shimada, I., Kondoh, Y., et al. (2014). The selective anaplastic lymphoma receptor tyrosine kinase inhibitor ASP3026 induces tumor regression and prolongs survival in non-small cell lung cancer model mice. Molecular Cancer Therapeutics, 13(2), 329–340. doi:10.1158/1535-7163.MCT-13-0395.

    Article  CAS  PubMed  Google Scholar 

  73. Maitland, L. M., Ou, S. I., Tolcher, A. W., LoRusso, P., Bahceci, E., Ball, H. A., et al. (2014). Safety, activity, and pharmacokinetics of an oral anaplastic lymphoma kinase (ALK) inhibitor, ASP3026, observed in a “fast follower” phase 1 trial design. Journal of Clinical Oncology, 32(5s), 2624.

    Google Scholar 

  74. Greenwald, R. J., Freeman, G. J., & Sharpe, A. H. (2005). The B7 family revisited. Annual Review of Immunology, 23, 515–548. doi:10.1146/annurev.immunol.23.021704.115611.

    Article  PubMed  Google Scholar 

  75. Teft, W. A., Kirchhof, M. G., & Madrenas, J. (2006). A molecular perspective of CTLA-4 function. Annual Review of Immunology, 24, 65–97. doi:10.1146/annurev.immunol.24.021605.090535.

    Article  CAS  PubMed  Google Scholar 

  76. Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., et al. (2002). Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nature Medicine, 8(8), 793–800. doi:10.1038/nm730.

    CAS  PubMed  Google Scholar 

  77. Freeman, G. J., Long, A. J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., et al. (2000). Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. Journal of Experimental Medicine, 192(7), 1027–1034.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  78. Dong, H., Zhu, G., Tamada, K., & Chen, L. (1999). B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nature Medicine, 5(12), 1365–1369. doi:10.1038/70932.

    Article  CAS  PubMed  Google Scholar 

  79. Wang, C., Thudium, K. B., Han, M., Wang, X. T., Huang, H., Feingersh, D., et al. (2014). In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates. Cancer Immunol Res, 2(9), 846–856. doi:10.1158/2326-6066.CIR-14-0040.

    Article  CAS  PubMed  Google Scholar 

  80. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427716.htm. Accessed Jan 25, 2015.

  81. http://meetinglibrary.asco.org/content/93154?format=posterImg. Accessed Jan 25, 2015.

  82. Brahmer, J. R., Horn, L., Gandhi, L., Spigel, D. R., Antonia, S. J., Rizvi, N. A., et al. (2014) Nivolumab (anti-PD-1,BMS-936558, ONO-4538) in patients (pts) with advanced non-small-cell lung cancer (NSCLC): Survival and clinical activity by subgroup analysis. Journal of Clinical Oncology, 32(5s). abstr 8112.

  83. https://clinicaltrials.gov/ct2/results?term=nivolumab++nsclc&Search=Search. Accessed Feb 10, 2015.

  84. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm412861.htm. Accessed Feb 10, 2015.

  85. Garon, E. B., Gandhi, L., Rizvi, N., Hui, R., Balmanoukian, A. S., Patnaik, A. et al. (2014). Antitumor activity ofpembrolizumab (Pembro; MK-3475) and correlation with programmed death ligand 1 (PD-L1) expression in a pooled analysis of patients (pts) with advanced non-small cell lung carcinoma (NSCLC). Annals of Oncology, 25(5):1-41. doi:10.1093/annonc/mdu438.

  86. http://www.esmo.org/Conferences/ESMO-2014-Congress/News-Articles/Pembrolizumab-Shows-Promise-in-Several-Solid-Tumours. Accessed Jan 25, 2015.

  87. https://clinicaltrials.gov/ct2/results?term=&recr=&rslt=&type=&cond=nsclc&intr=Pembrolizumab&titles=&outc=&spons=&lead=&id=&state1=&cntry1=&state2=&cntry2=&state3=&cntry3=&locn=&gndr=&rcv_s=&rcv_e=&lup_s=&lup_e=. Accessed Jan 25, 2015.

  88. Herbst, R. S., Soria, J. C., Kowanetz, M., Fine, G. D., Hamid, O., Gordon, M. S., et al. (2014). Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature, 515(7528), 563–567. doi:10.1038/nature14011.

    Article  CAS  PubMed  Google Scholar 

  89. Spigel, D. R., Scott, N. G., Horn, L., Herbst, R. S., Gandhi, L., Gordon, M. S., et al. (2013). Clinical activity,safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). Journal Clinical Oncology, 31(suppl), abstr 8008.

  90. https://clinicaltrials.gov/ct2/results?term=MPDL3280A+nsclc&Search=Search. Accessed Jan 25, 2015.

  91. Lutzk, J., Scott, J. A., Blake-Haskins, A., Li X., Robbins, P. B., Shalabi, A. M., et al. (2014). A phase 1 study ofMEDI4736, an anti–PD-L1 antibody, in patients with advanced solid tumors. Journal of Clinical Oncology, 32(5s), abstr 3001.

  92. https://clinicaltrials.gov/ct2/results?term=MEDI4736+nsclc&Search=Search. Accessed Jan 25, 2015.

  93. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm1193237.htm. Accessed Jan 25, 2015.

  94. Lynch, T. J., Bondarenko, I., Luft, A., Serwatowski, P., Barlesi, F., Chacko, R., et al. (2012). Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. Journal of Clinical Oncology, 30(17), 2046–2054. doi:10.1200/JCO.2011.38.4032.

    Article  CAS  PubMed  Google Scholar 

  95. https://clinicaltrials.gov/ct2/show/NCT02279732?term=IPILIMUMAB+nsclc&rank=6. Accessed Jan 25, 2015.

  96. https://clinicaltrials.gov/ct2/results?term=IPILIMUMAB+nsclc&Search=Search. Accessed Jan 25, 2015.

  97. Zatloukal, P., Heo, D. S., Park, K., Kang, J., Butts, C., Bradford, D., et al. (2009). Randomized phase IIclinical trial comparing tremelimumab (CP-675,206) with best supportive care (BSC) following first-line platinum-based therapy in patients (pts) with advanced non-small cell lung cancer (NSCLC). Journal Clinical Oncology, 27(15s), abstr 8071.

  98. https://clinicaltrials.gov/ct2/results?term=Tremelimumab+nsclc&Search=Search. Accessed Jan 25, 2015.

  99. Friboulet, L., Li, N., Katayama, R., Lee, C. C., Gainor, J. F., Crystal, A. S., et al. (2014). The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discovery, 4(6), 662–673. doi:10.1158/2159-8290.CD-13-0846.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  100. Sharma, P., Wagner, K., Wolchok, J. D., & Allison, J. P. (2011). Novel cancer immunotherapy agents with survival benefit: recent successes and next steps. Nature Reviews Cancer, 11(11), 805–812. doi:10.1038/nrc3153.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  101. Melero, I., Grimaldi, A. M., Perez-Gracia, J. L., & Ascierto, P. A. (2013). Clinical development of immunostimulatory monoclonal antibodies and opportunities for combination. Clinical Cancer Research, 19(5), 997–1008. doi:10.1158/1078-0432.CCR-12-2214.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Supported by a Conquer Cancer Foundation Drug Development Research Professorship (AAA).

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  1. Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA

    Yujie Zhao & Alex A. Adjei

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  1. Yujie Zhao
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Correspondence to Alex A. Adjei.

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Zhao, Y., Adjei, A.A. New strategies to develop new medications for lung cancer and metastasis. Cancer Metastasis Rev 34, 265–275 (2015). https://doi.org/10.1007/s10555-015-9553-5

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