PIK3CB

Overview

PIK3CB encodes the p110β catalytic subunit of phosphoinositide 3-kinase (PI3K). Activating mutations at positions equivalent to canonical PIK3CA hotspots were discovered in metastatic castration-resistant prostate cancer (mCRPC), where they co-occur with PTEN loss and may respond to PIK3CB-specific inhibitors.

Alterations observed in the corpus

  • In mCRPC, PIK3CB mutations were observed for the first time at positions equivalent to canonical PIK3CA hotspots; they co-occur in the context of PTEN deficiency. PIK3CB also harbors focal amplifications and novel activating fusions resulting in PIK3CB overexpression. PIK3CB mutations/amplifications/fusions contribute to the PI3K pathway alteration in 49% (73/150) of the SU2C–PCF prospective cohort. PMID:26000489
  • Mutated in 2 PTEN-homozygous-deleted prostate tumors (E552K, paralogous to PIK3CA helical-domain hotspot); combined PI3K/AR inhibition suggested for PTEN-deleted/PIK3CB-mutant cases PMID:26544944

Cancer types (linked)

  • PRAD (mCRPC): activating mutations, amplifications, and gene fusions; frequently co-occurring with biallelic PTEN loss. PMID:26000489

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • PIK3CB-specific inhibitors may have utility in mCRPC patients with PIK3CB mutation, amplification, or fusion; authors cite durable (>1 year) responses to PIK3CB-specific inhibition in carriers of activating PIK3CB alterations (de Bono 2015). PMID:26000489

Open questions

  • The relative contribution of PIK3CB vs PIK3CA alterations in PI3K-pathway-driven mCRPC, and optimal inhibitor strategy, requires prospective clinical validation.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:26544944

This page was processed by crosslinker on 2026-05-14.