Profile of imatinib in pediatric leukemia

Burke, Michael J.
January 2014
Pediatric Health, Medicine & Therapeutics;2014, Vol. 5, p1
Academic Journal
Using targeted therapy for treatment of cancer has become the paradigm to which clinical trials aspire. Imatinib, the BCR-ABL1 tyrosine kinase inhibitor (TKI), was the first of its kind to specifically target and inhibit the underlying Philadelphia chromosome (Ph+) oncogene found to be driving chronic myeloid leukemia in adults, and has since become standard of care for the treatment of chronic myeloid leukemia in children. Imatinib, with its ability to target Ph+ leukemia, has been successfully incorporated into the treatment of not only pediatric chronic myeloid leukemia but also Ph+ acute lymphoblastic leukemia. With the incorporation of imatinib into combination chemotherapy for pediatric Ph+ acute lymphoblastic leukemia, current survival rates are far higher than at any other time for this once dreadful disease. With more children today receiving treatment with imatinib for either chronic myeloid leukemia or Ph+ acute lymphoblastic leukemia, knowledge is accumulating surrounding the short-term and long-term toxicities observed in children, adolescents, and young adults treated with this TKI. In summary, the TKI imatinib has made a historic impact in the treatment of pediatric Ph+ leukemias, transforming what were once very high-risk diseases with considerable morbidity and mortality into ones that are now very treatable but with a new awareness surrounding the long-term toxicities that may come with this price for cure.


Related Articles

  • Tyrosine Kinase Blockers: New Hope for Successful Cancer Therapy. Pytel, Dariusz; Sliwinski, Tomasz; Poplawski, Tomasz; Ferriola, Deborah; Majsterek, Ireneusz // Anti-Cancer Agents in Medicinal Chemistry;2009, Vol. 9 Issue 1, p66 

    Tyrosine kinases (TKs) are attractive targets for cancer therapy, as quite often their abnormal signaling has been linked with tumor development and growth. Constitutive activated TKs stimulate multiple signaling pathways responsible for DNA repair, apoptosis, and cell proliferation. During the...

  • Anticancer Drugs: Partnering to promote apoptosis. Harrison, Charlotte // Nature Reviews Drug Discovery;Oct2008, Vol. 7 Issue 10, p805 

    The article relates on two studies that highlight how combining novel anticancer agents that target apoptotic pathways with other approved drugs can enhance tumour-cell apoptosis. The first study investigated whether resistance to imatinib could be overcome by targeting inhibitor of apoptosis...

  • Anorectal melanoma with a KIT-activating mutation, which is a target for tyrosine kinase inhibitor. Itoh, Miki; Goto, Akira; Wakasugi, Hideki; Yoshida, Yutaka; Matsunaga, Yasutaka; Fujii, Kenichi; Suzuki, Kazuya; Yonezawa, Kazuhiko; Abe, Takashi; Arimura, Yoshiaki; Shinomura, Yasuhisa // International Journal of Clinical Oncology;Aug2011, Vol. 16 Issue 4, p428 

    Recent advances in our understanding of the genetic mutations associated with melanoma have led to the classification of distinct melanoma subtypes. A number of reports have consistently demonstrated that mucosal and acral melanomas more commonly harbor KIT-activating mutations than do other...

  • MOLECULAR TESTING IN GASTROINTESTINAL STROMAL TUMOURS - WE'VE GOT THE GIST OF IT, NOW LET'S GO FORWARD. Allen, Caroline S.; Streutker, Catherine J. // Canadian Journal of Pathology;2018, Vol. 10 Issue 3, p9 

    Molecular testing in gastrointestinal stromal tumours has expanded beyond the original discovery of cKIT mutations. Molecular analysis is essential for diagnosis, prognostication and treatment of these tumours.

  • Rapid initial decline in BCR-ABL1 is associated with superior responses to second-line nilotinib in patients with chronic-phase chronic myeloid leukemia. Stein, Andrew M.; Martinelli, Giovanni; Hughes, Timothy P.; Müller, Martin C.; Beppu, Lan; Gottardi, Enrico; Branford, Susan; Soverini, Simona; Woodman, Richard C.; Hochhaus, Andreas; Dong-Wook Kim; Saglio, Giuseppe; Radich, Jerald P. // BMC Cancer;2013, Vol. 13 Issue 1, p1 

    Background: We evaluated BCR-ABL1 kinetics in patients treated with nilotinib and analyzed whether a dynamic model of changes in BCR-ABL1 levels over time could be used to predict long-term responses. Methods: Patients from the nilotinib registration trial (CAMN107A2101; registered at...

  • Surgery after treatment with imatinib and/or sunitinib in patients with metastasized gastrointestinal stromal tumors: is it worthwhile? Tielen, Ronald; Verhoef, Cornelis; van Coevorden, Frits; Gelderblom, Hans; Sleijfer, Stefan; Hartgrink, Henk H.; Bonenkamp, Johannes J.; van der Graaf, Winette T.; de Wilt, Johannes H. W. // World Journal of Surgical Oncology;2012, Vol. 10 Issue 1, p111 

    Background: Standard treatment for metastatic gastrointestinal stromal tumors (GISTs) is systemic therapy with imatinib. Surgery is performed to remove metastatic lesions to induce long-term remission or even curation. In other patients, surgery is performed to remove (focal) progressive or...

  • Impact of malignant stem cell burden on therapy outcome in newly diagnosed chronic myeloid leukemia patients. Mustjoki, S; Richter, J; Barbany, G; Ehrencrona, H; Fioretos, T; Gedde-Dahl, T; Gjertsen, B T; Hovland, R; Hernesniemi, S; Josefsen, D; Koskenvesa, P; Dybedal, I; Markevärn, B; Olofsson, T; Olsson-Strömberg, U; Rapakko, K; Thunberg, S; Stenke, L; Simonsson, B; Porkka, K // Leukemia (08876924);Jul2013, Vol. 27 Issue 7, p1520 

    Chronic myeloid leukemia (CML) stem cells appear resistant to tyrosine kinase inhibitors (TKIs) in vitro, but their impact and drug sensitivity in vivo has not been systematically assessed. We prospectively analyzed the proportion of Philadelphia chromosome-positive leukemic stem cells (LSCs,...

  • A population study of imatinib in chronic myeloid leukaemia demonstrates lower efficacy than in clinical trials. Lucas, C. M.; Wang, L.; Austin, G. M.; Knight, K.; Watmough, S. J.; Shwe, K. H.; Dasgupta, R.; Butt, Nauman M.; Galvani, D.; Hoyle, C. F.; Seale, J. R. C.; Clark, R. E. // Leukemia (08876924);Oct2008, Vol. 22 Issue 10, p1963 

    The article discusses the significance of imatinib, a tyrosine kinase inihibitor to the patients with chronic myeloid leukaemia (CML). It says that imatinib has become the treatment of choice for newly diagnosed patients in chronic phase. Further, imatinib-treated cohort within the International...

  • Phase I trial of sunitinib and gemcitabine in patients with advanced solid tumors. Brell, Joanna; Krishnamurthi, Smitha; Rath, Linda; Bokar, Joseph; Savvides, Panayiotis; Gibbons, Joseph; Cooney, Matthew; Meropol, Neal; Ivy, Percy; Dowlati, Afshin // Cancer Chemotherapy & Pharmacology;Oct2012, Vol. 70 Issue 4, p547 

    Purpose: Combining cytotoxic agents with bevacizumab has yielded significant benefits in a number of solid tumors. Combining small-molecule kinase inhibitors of VEGFR with chemotherapy has yet to demonstrate clinical benefit. The dose, schedule and agents used may be critical to the development...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics