PI3K

The Role of PI3K in B-Cell Malignancies

The phosphoinositide-3-kinase (PI3K) pathway is known to play a critical role in regulating the growth and survival of certain types of cancers. (PI3K)-delta and PI3K-gamma are two proteins that are known to help support the growth and survival of malignant B-cells. PI3K signaling may lead to the proliferation of malignant B-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment. 1-3 As such, PI3K-delta and PI3K-gamma represent potential therapeutic targets for the treatment of a broad range of cancers.

Learn More About the Role of PI3K-Delta and PI3K-Gamma Inhibition in Blood Cancers:

 

The Role of PI3K in Solid Tumors 

 The PI3 kinases (PI3K) belong to a family of signal-transducing enzymes that mediate key cellular functions in cancer and immunity. The PI3K-gamma isoform plays an important role in immune cell function and migration, as well as supporting the function of myeloid cells in the tumor microenvironment.4 Because of this, targeting PI3K-gamma in immune cells could alter the balance from an immune-suppressive to a pro-inflammatory environment, leading to tumor growth inhibition.5,6

 

[1] Winkler D.G., Faia K.L., DiNitto J.P. et al. (2013) PI3K-d and PI3K-g inhibition by IPI_145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol 20: 1-11.
[2] Reif K et al.Cutting Edge: Differential Roles for Phosphoinositide 3 kinases, p110-gamma and p110-delta, in lymphocyte chemotaxis and homing. J Immunol 2004:173:2236-2240.

[3] Schmid M et al. Receptor Tyrosine Kinases and TLR/IL1Rs Unexpectedly activate myeloid cell PI3K, a single convergent point promoting tumor inflammation and progression. Cancer Cell 2011;19:715-727.

[4] Schmid et al. 2011, Cancer Cell 19:715
[5] Joshi et al. 2014, Mol Canc Res12:1520

[6] Gunderson et al. 2016 Cancer Discovery in press.

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