TY - JOUR
T1 - Duvelisib
T2 - a phosphoinositide-3 kinase δ/γ inhibitor for chronic lymphocytic leukemia
AU - Vangapandu, Hima V.
AU - Jain, Nitin
AU - Gandhi, Varsha
N1 - Publisher Copyright:
© 2017 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2017/5/4
Y1 - 2017/5/4
N2 - Introduction: Frontline chemotherapy is successful against chronic lymphocytic leukemia (CLL), but results in untoward toxicity. Further, prognostic factors, cytogenetic anomalies, and compensatory cellular signaling lead to therapy resistance or disease relapse. Therefore, for the past few years, development of targeted therapies is on the rise. PI3K is a major player in the B-cell receptor (BCR) signaling axis, which is critical for the survival and maintenance of B cells. Duvelisib, a PI3K δ/γ dual isoform specific inhibitor that induces apoptosis and reduces cytokine and chemokine levels in vitro, holds promise for CLL. Areas covered: Herein, we review PI3K isoforms and their inhibitors in general, and duvelisib in particular; examine literature on preclinical investigations, pharmacokinetics and clinical studies of duvelisib either as single agent or in combination, for patients with CLL and other lymphoid malignancies. Expert opinion: Duvelisib targets the PI3K δ isoform, which is necessary for cell proliferation and survival, and γ isoform, which is critical for cytokine signaling and pro-inflammatory responses from the microenvironment. In phase I clinical trials, duvelisib as a single agent showed promise for CLL and other lymphoid malignancies. Phase II and III trials of duvelisib alone or in combination with other agents are ongoing.
AB - Introduction: Frontline chemotherapy is successful against chronic lymphocytic leukemia (CLL), but results in untoward toxicity. Further, prognostic factors, cytogenetic anomalies, and compensatory cellular signaling lead to therapy resistance or disease relapse. Therefore, for the past few years, development of targeted therapies is on the rise. PI3K is a major player in the B-cell receptor (BCR) signaling axis, which is critical for the survival and maintenance of B cells. Duvelisib, a PI3K δ/γ dual isoform specific inhibitor that induces apoptosis and reduces cytokine and chemokine levels in vitro, holds promise for CLL. Areas covered: Herein, we review PI3K isoforms and their inhibitors in general, and duvelisib in particular; examine literature on preclinical investigations, pharmacokinetics and clinical studies of duvelisib either as single agent or in combination, for patients with CLL and other lymphoid malignancies. Expert opinion: Duvelisib targets the PI3K δ isoform, which is necessary for cell proliferation and survival, and γ isoform, which is critical for cytokine signaling and pro-inflammatory responses from the microenvironment. In phase I clinical trials, duvelisib as a single agent showed promise for CLL and other lymphoid malignancies. Phase II and III trials of duvelisib alone or in combination with other agents are ongoing.
KW - CLL
KW - PI3K
KW - duvelisib
KW - leukemia
KW - therapy
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U2 - 10.1080/13543784.2017.1312338
DO - 10.1080/13543784.2017.1312338
M3 - Article
C2 - 28388280
AN - SCOPUS:85017474758
SN - 1354-3784
VL - 26
SP - 625
EP - 632
JO - Expert Opinion on Investigational Drugs
JF - Expert Opinion on Investigational Drugs
IS - 5
ER -