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Editorial
. 2014 Mar 13;370(11):1061-2.
doi: 10.1056/NEJMe1400055.

Idelalisib--a PI3Kδ inhibitor for B-cell cancers

David A Fruman  1 , Lewis C Cantley
Affiliations
Editorial

Idelalisib--a PI3Kδ inhibitor for B-cell cancers

David A Fruman et al. N Engl J Med. .
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1. Mechanism of Action of Idelalisib and Ibrutinib
B-cell receptor (BCR) signaling activates phosphoinositide 3-kinase (PI3K) to produce the second messenger, phosphatidylinositol 3,4,5-trisphosphate (PIP3), which activates Bruton’s tyrosine kinase (BTK) and AKT, a prosurvival kinase that binds PIP3 and plays a key role in many solid tumors. Idelalisib, a selective inhibitor of the delta isoform of PI3K, targets signal transduction downstream of the BCR in malignant B cells, whereas ibrutinib targets BTK. PI3K and BTK are also activated downstream of numerous other receptors on B cells, including CD40, cytokine receptors, chemokine receptors, and toll-like receptors (TLRs). The BCR is composed of antibody heavy and light chains associated with two signaling chains, Igα and Igβ.
See this image and copyright information in PMC

Comment on

  • Idelalisib and rituximab in relapsed chronic lymphocytic leukemia.
    Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, Barrientos JC, Zelenetz AD, Kipps TJ, Flinn I, Ghia P, Eradat H, Ervin T, Lamanna N, Coiffier B, Pettitt AR, Ma S, Stilgenbauer S, Cramer P, Aiello M, Johnson DM, Miller LL, Li D, Jahn TM, Dansey RD, Hallek M, O'Brien SM. Furman RR, et al. N Engl J Med. 2014 Mar 13;370(11):997-1007. doi: 10.1056/NEJMoa1315226. Epub 2014 Jan 22. N Engl J Med. 2014. PMID: 24450857 Free PMC article. Clinical Trial.
  • PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma.
    Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, Blum KA, Goy AH, Davies AJ, Zinzani PL, Dreyling M, Johnson D, Miller LL, Holes L, Li D, Dansey RD, Godfrey WR, Salles GA. Gopal AK, et al. N Engl J Med. 2014 Mar 13;370(11):1008-18. doi: 10.1056/NEJMoa1314583. Epub 2014 Jan 22. N Engl J Med. 2014. PMID: 24450858 Free PMC article. Clinical Trial.

References

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    1. Klempner SJ, Myers AP, Cantley LC. What a tangled web we weave: emerging resistance mechanisms to inhibition of the phosphoinositide 3-kinase pathway. Cancer Discov. 2013;3:1345–1354. - PMC - PubMed
    1. Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370:997–1007. - PMC - PubMed
    1. Gopal AK, Kahl BS, de Vos S, et al. PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014;370:1008–1018. - PMC - PubMed
    1. Ten Hacken E, Burger JA. Molecular pathways: targeting the microenvironment in chronic lymphocytic leukemia — focus on the B-cell receptor. Clin Cancer Res. 2014;20:548–556. - PubMed

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