Issue Date
2015-07-17Keywords
CANCERMULTIPLE MYELOMA
MeSH
AnimalsAntineoplastic Agents
Cell Proliferation
Drug Resistance, Neoplasm
Gene Expression Regulation, Neoplastic
Humans
Molecular Targeted Therapy
Multiple Myeloma
Protein Kinase Inhibitors
Proto-Oncogene Proteins c-pim-1
Signal Transduction
Up-Regulation
Metadata
Show full item recordCitation
Targeting the Pim kinases in multiple myeloma. 2015, 5:e325 Blood Cancer JPublisher
Nature Publishing GroupJournal
Blood cancer journalDOI
10.1038/bcj.2015.46PubMed ID
26186558Abstract
Multiple myeloma (MM) is a plasma cell malignancy that remains incurable. Novel treatment strategies to improve survival are urgently required. The Pims are a small family of serine/threonine kinases with increased expression across the hematological malignancies. Pim-2 shows highest expression in MM and constitutes a promising therapeutic target. It is upregulated by the bone marrow microenvironment to mediate proliferation and promote MM survival. Pim-2 also has a key role in the bone destruction typically seen in MM. Additional putative roles of the Pim kinases in MM include trafficking of malignant cells, promoting oncogenic signaling in the hypoxic bone marrow microenvironment and mediating resistance to therapy. A number of Pim inhibitors are now under development with lead compounds entering the clinic. The ATP-competitive Pim inhibitor LGH447 has recently been reported to have single agent activity in MM. It is anticipated that Pim inhibition will be of clinical benefit in combination with standard treatments and/or with novel drugs targeting other survival pathways in MM.Item Type
ArticleLanguage
enISSN
2044-5385ae974a485f413a2113503eed53cd6c53
10.1038/bcj.2015.46
Scopus Count
Collections
Related articles
- Inhibitors of the Cyclin-Dependent Kinase and PIM Kinase Pathways in the Treatment of Myeloma.
- Authors: Ramakrishnan VG, Kumar SK
- Issue date: 2016 Jan-Feb
- The Novel Pan-PIM Kinase Inhibitor, PIM447, Displays Dual Antimyeloma and Bone-Protective Effects, and Potently Synergizes with Current Standards of Care.
- Authors: Paíno T, Garcia-Gomez A, González-Méndez L, San-Segundo L, Hernández-García S, López-Iglesias AA, Algarín EM, Martín-Sánchez M, Corbacho D, Ortiz-de-Solorzano C, Corchete LA, Gutiérrez NC, Maetos MV, Garayoa M, Ocio EM
- Issue date: 2017 Jan 1
- Use of regulators and inhibitors of Pim-1, a serine/threonine kinase, for tumour therapy (review).
- Authors: Liang C, Li YY
- Issue date: 2014 Jun
- Preclinical characterization of INCB053914, a novel pan-PIM kinase inhibitor, alone and in combination with anticancer agents, in models of hematologic malignancies.
- Authors: Koblish H, Li YL, Shin N, Hall L, Wang Q, Wang K, Covington M, Marando C, Bowman K, Boer J, Burke K, Wynn R, Margulis A, Reuther GW, Lambert QT, Dostalik Roman V, Zhang K, Feng H, Xue CB, Diamond S, Hollis G, Yeleswaram S, Yao W, Huber R, Vaddi K, Scherle P
- Issue date: 2018
- Biological effects of the Pim kinase inhibitor, SGI-1776, in multiple myeloma.
- Authors: Cervantes-Gomez F, Chen LS, Orlowski RZ, Gandhi V
- Issue date: 2013 Sep