Potential Therapies for Anaplastic Lymphoma Kinase-Driven Tumors in Children: Progress to Date
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Anaplastic lymphoma kinase (ALK) is an oncogenic tyrosine kinase that is deregulated due to a variety of molecular mechanisms in pediatric cancer. They include chromosomal translocations, activation mutations, and gene amplifications. Since the initial discovery of ALK as an oncogenic tyrosine kinase involved in the chromosomal translocation t(2, 5)(p23;q35) in 1994, more than 20 translocation partners of ALK have been identified in various cancers. Furthermore, deregulation of ALK tyrosine kinase activity is critical for the pathogenesis of several other pediatric tumors, including neuroblastomas and inflammatory myofibroblastic tumors. The recent discovery of ALK translocations in adult lung cancer patients (non-small cell lung cancer) has accelerated the development of inhibitors of ALK tyrosine kinase as therapeutic agents. While excellent clinical response has been observed in many patients, the acquisition of clinical resistance to ALK inhibition highlights the need for development of second-generation ALK kinase inhibitors and/or combination therapies that target downstream signaling mediators or antibody drug conjugates. This article provides an update on the spectrum of ALK-driven tumors in the pediatric population and the potential therapies which target these tumors.
KeywordsAnaplastic Lymphoma Kinase Anaplastic Large Cell Lymphoma Crizotinib Inflammatory Myofibroblastic Tumor Anaplastic Lymphoma Kinase Inhibitor
The authors have no conflicts of interest or sources of funding to declare.
- 10.Stein H, Mason DY, Gerdes J, O’Connor N, Wainscoat J, Pallesen G, et al. The expression of the Hodgkin’s disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed–Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood. 1985;66(4):848–58.PubMedGoogle Scholar
- 11.Swerdlow SH, Campo E, Harris NL, Jaffé E, Pileri S, Stein H, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC; 2008.Google Scholar
- 13.Laver JH, Kraveka JM, Hutchison RE, Chang M, Kepner J, Schwenn M, et al. Advanced-stage large-cell lymphoma in children and adolescents: results of a randomized trial incorporating intermediate-dose methotrexate and high-dose cytarabine in the maintenance phase of the APO regimen: a Pediatric Oncology Group phase III trial. J Clin Oncol. 2005;23(3):541–7.PubMedCrossRefGoogle Scholar
- 16.Seidemann K, Tiemann M, Schrappe M, Yakisan E, Simonitsch I, Janka-Schaub G, et al. Short-pulse B-non-Hodgkin lymphoma-type chemotherapy is efficacious treatment for pediatric anaplastic large cell lymphoma: a report of the Berlin-Frankfurt-Munster group trial NHL-BFM 90. Blood. 2001;97(12):3699–706.PubMedCrossRefGoogle Scholar
- 17.Woessmann W, Peters C, Lenhard M, Burkhardt B, Sykora KW, Dilloo D, et al. Allogeneic haematopoietic stem cell transplantation in relapsed or refractory anaplastic large cell lymphoma of children and adolescents: a Berlin-Frankfurt-Munster group report. Br J Haematol. 2006;133(2):176–82.PubMedCrossRefGoogle Scholar
- 19.Matthay KK, Villablanca JG, Seeger RC, Stram DO, Harris RE, Ramsay NK, et al. Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. Children’s Cancer Group. N Engl J Med. 1999;341(16):1165–73.PubMedCrossRefGoogle Scholar
- 26.Christensen JG, Zou HY, Arango ME, Li Q, Lee JH, McDonnell SR, et al. Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma. Mol Cancer Ther. 2007;6(12 Pt 1):3314–22.PubMedCrossRefGoogle Scholar
- 28.US Food and Drug Administration. FDA labeling information—Xalkori®. 2011. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202570s000lbl.pdf. Accessed July 2012.
- 30.Stasia A, Guerra L, Berbard L, Cohen A, King M, Ordemann R, et al. Crizotinib obtains durable responses in advanced chemoresistant ALK + lymphoma patients [abstract no. 1153]. Haematologica. 2012;97(Suppl):478.Google Scholar
- 31.Mosse YP, Balis FM, Lim MS, Laliberte J, Voss SD, Fox E, et al. Efficacy of crizotinib in children with relapsed/refractory ALK-driven tumors including anaplastic large cell lymphoma and neuroblastoma: a Children’s Oncology Group phase I consortium study. J Clin Oncol. 2012;30(Suppl; abstr 9500).Google Scholar
- 32.Zhang S, Wang F, Keats J, Ning Y, Wardwell SD. AP26113, a potent ALK inhibitor, overcomes mutations in EML4-ALK that confer resistance to PF-02341066 (PF1066). Proc Am Assoc Cancer Res. 2010;51:abstract LB-298.Google Scholar
- 33.Kiura K, Seto T, Yamamoto N, Nishio M, Nakagawa K, Tamura T. A first-in-human phase I/II study of ALK inhibitor CH5424802 in patients with ALK-positive NSCLC. J Clin Oncol. 2012;30(Suppl; abstr 7602).Google Scholar
- 34.Mehra R, Camidge DR, Sharma S, Felip E, Tan D, Vansteenkiste JF, et al. First-in-human phase I study of the ALK inhibitor LDK378 in advanced solid tumors. J Clin Oncol. 2012;30(Suppl; abstr 3007).Google Scholar
- 35.Kuromitsu S, Mori M, Shimada I, Kondoh Y, Shindoh N, Soga T, et al. Antitumor activities of ASP3026 against EML4-ALK-dependent tumor models. In: Proceedings of the AACR-NCI-EORTC international conference 12–16 Nov 2011. Mol Cancer Ther. 2011;10(11 Suppl):abstract A227.Google Scholar
- 40.Ait-Tahar K, Damm-Welk C, Burkhardt B, Zimmermann M, Klapper W, Reiter A, et al. Correlation of the autoantibody response to the ALK oncoantigen in pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with tumor dissemination and relapse risk. Blood. 2010;115(16):3314–9.PubMedCrossRefGoogle Scholar
- 43.Lewis RT, Bode CM, Choquette DM, Potashman M, Romero K, Stellwagen JC, et al. The discovery and optimization of a novel class of potent, selective, and orally bioavailable anaplastic lymphoma kinase (ALK) inhibitors with potential utility for the treatment of cancer. J Med Chem. 2012;55(14):6523–40.PubMedCrossRefGoogle Scholar