Drug Resistance, Neoplasm
Gene Expression Regulation, Neoplastic
Molecular Targeted Therapy
Protein Kinase Inhibitors
Proto-Oncogene Proteins c-pim-1
MetadataShow full item record
CitationTargeting the Pim kinases in multiple myeloma. 2015, 5:e325 Blood Cancer J
PublisherNature Publishing Group
JournalBlood cancer journal
AbstractMultiple 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.
- 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
- Pan-PIM kinase inhibitors enhance Lenalidomide's anti-myeloma activity via cereblon-IKZF1/3 cascade.
- Authors: Zheng J, Sha Y, Roof L, Foreman O, Lazarchick J, Venkta JK, Kozlowski C, Gasparetto C, Chao N, Ebens A, Hu J, Kang Y
- Issue date: 2019 Jan