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The blood-cell version of the PI3K survival signal that keeps B cells alive. Idelalisib, duvelisib and copanlisib block it in chronic lymphocytic leukaemia and follicular lymphoma, at the price of immune-related colitis, liver inflammation and infections that have limited their use.
The delta isoform of PI3K is restricted to white blood cells and relays B-cell receptor signalling, so blocking it starves malignant B cells of a survival signal. Idelalisib was approved in 2014 for relapsed CLL with rituximab and for follicular lymphoma, duvelisib in 2018 and copanlisib in 2017, but autoimmune-type toxicities, opportunistic infections and unfavourable survival signals in confirmatory trials led to the withdrawal of the follicular lymphoma indications in 2022 and of copanlisib in 2023. BTK inhibitors and venetoclax have largely taken their place, and the class is a case study in the limits of accelerated approval.
In plain words · The blood-cell version of the PI3K survival signal that keeps B cells alive. Idelalisib, duvelisib and copanlisib block it in chronic lymphocytic leukaemia and follicular lymphoma, at the price of immune-related colitis, liver inflammation and infections that have limited their use.
The blood-cell version of the PI3K survival signal that keeps B cells alive. Idelalisib, duvelisib and copanlisib block it in chronic lymphocytic leukaemia and follicular lymphoma, at the price of immune-related colitis, liver inflammation and infections that have limited their use.
Leukocyte-restricted class I PI3K catalytic subunit downstream of the B-cell receptor; isoform-selective inhibitors spare the ubiquitous alpha and beta isoforms.
No product in this corpus aims at PI3K delta (PIK3CD) yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
Lineage antigen shared with normal bone marrow cells and lymphoid tissue cells: HPA finds the gene tissue enhanced in bone marrow, lymphoid tissue, and the 3 medicines aimed at it (Idelalisib, Duvelisib, Copanlisib) act on the wild-type protein, so the normal lineage is hit too. HPA PIK3CD: RNA tissue enhanced (bone marrow 44 nTPM, lymphoid tissue 45 nTPM); no normal tissue stained high. Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Leukaemia, Lymphoma); Open Targets associates it with 4 specific cancer types at or above 0.5 (B-cell chronic lymphocytic leukemia, follicular lymphoma, non-Hodgkin lymphoma, marginal zone lymphoma). (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas PIK3CD tissue; Human Protein Atlas PIK3CD pathology; Open Targets ENSG00000171608 associations
First described 1997. Earliest sequence paper UniProt cites for the protein: Vanhaesebroeck B.A.M. et al, Proc. Natl. Acad. Sci. U.S.A, 1997, "P110delta, a novel phosphoinositide 3-kinase in leukocytes". Source.
Leukocyte-restricted class I PI3K catalytic subunit downstream of the B-cell receptor; isoform-selective inhibitors spare the ubiquitous alpha and beta isoforms.
RNA: tissue enhanced (bone marrow 44 nTPM, lymphoid tissue 45 nTPM), detected in many normal tissues.
No normal tissue stained high; medium in Appendix, Lymph node, Testis, Tonsil.
No cancer stained high; medium in lymphoma, pancreatic cancer, skin cancer.
HPA PIK3CD tissue · HPA PIK3CD pathology · HPA protein class: FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Chronic lymphocytic leukaemia | all% | PI3K delta is the B-cell form of the enzyme, present in essentially every B-cell malignancy; drugs are chosen by disease, not by a test | cancer.gov |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Query for this target: (TITLE:"PI3K delta" OR ABSTRACT:"PI3K delta" OR TITLE:"PIK3CD" OR ABSTRACT:"PIK3CD") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about PI3K delta (PIK3CD), not a curated reading list.
Shares Duvelisib, Chronic lymphocytic leukaemia.
Shares Copanlisib, Duvelisib, Idelalisib.
Shares TG Therapeutics, Follicular lymphoma, Chronic lymphocytic leukaemia.
Shares Copanlisib, Duvelisib, Idelalisib, Follicular lymphoma.
Shares Idelalisib, Chronic lymphocytic leukaemia.
Shares Idelalisib, Chronic lymphocytic leukaemia.