{"entity":{"id":"pik3cd","kind":"target","name":"PI3K delta (PIK3CD)","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/PIK3CD","links":[{"label":"UniProt O00329: PIK3CD","url":"https://www.uniprot.org/uniprotkb/O00329/entry"}],"tags":[],"related":[],"cancers":["cll","follicular-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["idelalisib","duvelisib","copanlisib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"PIK3CD","role":[],"sources":[],"specificity":"lineage-antigen","distribution":"few-types","specificityNote":"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.)","specificitySources":[{"label":"Human Protein Atlas PIK3CD tissue","url":"https://www.proteinatlas.org/ENSG00000171608-PIK3CD/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas PIK3CD pathology","url":"https://www.proteinatlas.org/ENSG00000171608-PIK3CD/pathology","note":"patients per staining level per cancer type (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000171608 associations","url":"https://platform.opentargets.org/target/ENSG00000171608/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:8977","ensembl":"ENSG00000171608","uniprot":"O00329","entrez":"5293","firstDescribed":1997,"firstDescribedBasis":"sequence","firstDescribedNote":"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\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/9113989/","biology":"Leukocyte-restricted class I PI3K catalytic subunit downstream of the B-cell receptor; isoform-selective inhibitors spare the ubiquitous alpha and beta isoforms.","whereFound":["Chronic lymphocytic leukaemia","Follicular lymphoma"],"targetClass":"kinase","prevalence":[{"cancerId":"cll","pct":"all","measure":"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","source":"https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq"}]},"route":"/targets/pik3cd/","neighbours":{"cancer":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"follicular-lymphoma","kind":"cancer","name":"Follicular lymphoma","route":"/cancers/follicular-lymphoma/"}],"drug":[{"id":"copanlisib","kind":"drug","name":"Copanlisib","route":"/drugs/copanlisib/"},{"id":"duvelisib","kind":"drug","name":"Duvelisib","route":"/drugs/duvelisib/"},{"id":"idelalisib","kind":"drug","name":"Idelalisib","route":"/drugs/idelalisib/"}],"company":[{"id":"mei-pharma","kind":"company","name":"MEI Pharma","route":"/companies/mei-pharma/"},{"id":"securabio","kind":"company","name":"SecuraBio","route":"/companies/securabio/"},{"id":"tg-therapeutics","kind":"company","name":"TG Therapeutics","route":"/companies/tg-therapeutics/"}]}}