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PTEN is the brake on the PI3K growth pathway; when a tumour loses it the pathway runs unchecked, which is why PTEN loss now selects patients for the AKT inhibitor capivasertib.
PTEN is a lipid phosphatase that converts PIP3 back to PIP2, opposing PI3K and switching off AKT signalling. Loss through deletion, mutation or promoter silencing is common in prostate, endometrial, breast and brain tumours and in Cowden syndrome when inherited. Capivasertib's labels name PTEN alterations (with PIK3CA and AKT1) in breast cancer and PTEN deficiency by immunohistochemistry in prostate cancer, so the readout pages under this target carry both the sequencing and the IHC rules.
In plain words · PTEN is the brake on the PI3K growth pathway; when a tumour loses it the pathway runs unchecked, which is why PTEN loss now selects patients for the AKT inhibitor capivasertib.
PTEN is the brake on the PI3K growth pathway; when a tumour loses it the pathway runs unchecked, which is why PTEN loss now selects patients for the AKT inhibitor capivasertib.
PTEN loss raises PIP3 and constitutively activates AKT and mTOR; it also has nuclear roles in genome stability, so PTEN-null tumours accumulate further damage.
No product in this corpus aims at PTEN yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
Tumour-specific alteration: 1 of 1 label readouts filed under it measure a sequence variant (PTEN alteration (sequencing) and PTEN loss (IHC)) absent from normal cells. HPA PTEN: RNA low tissue specificity; high antibody staining in 14 normal tissues; highest cancer staining head and neck cancer (2 of 4 high). Distribution: 4 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Prostate cancer, Breast cancer (all types), Endometrial cancer, Brain and spinal cord tumours (all types)); Open Targets associates it with 34 specific cancer types at or above 0.5 (PTEN hamartoma tumor syndrome, glioma susceptibility 2, Bannayan-Riley-Ruvalcaba syndrome, glioma, endometrial cancer, melanoma and more). (Rule 3 of scripts/fetch-target-specificity.ts.)
Sources: PTEN alteration (sequencing) and PTEN loss (IHC) label threshold; Human Protein Atlas PTEN tissue; Open Targets ENSG00000171862 associations
First described 1997. Earliest sequence paper UniProt cites for the protein: Li D.M. et al, Cancer Res, 1997, "TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
PTEN loss raises PIP3 and constitutively activates AKT and mTOR; it also has nuclear roles in genome stability, so PTEN-null tumours accumulate further damage.
RNA: low tissue specificity, detected in all normal tissues.
Medium: Breast, Caudate, Cerebral cortex, Cervix, Duodenum, Epididymis, Gallbladder, Heart muscle.
Medium only: cervical cancer, endometrial cancer, glioma, lung cancer.
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 |
|---|---|---|---|---|
| Prostate cancer | 12-41% | Deep deletion, and inactivating mutation on top of it | cBioPortal deep deletion: 85 of 489, 17.4%, in prad_tcga_pan_can_atlas_2018; 50 of 333, 15.0%, in prad_tcga_pub; 124 of 1,013, 12.2%, in prad_p1000; 61 of 424, 14.4%, in prad_mcspc_mskcc_2020; 262 of 2,260, 11.6%, in prostate_msk_2024; 209 of 1,465, 14.3%, in prad_cdk12_mskcc_2020; 114 of 444, 25.7%, in prad_su2c_2019; 41 of 150, 27.3%, in prad_su2c_2015; 55 of 149, 36.9%, in prad_fhcrc; 25 of 61, 41.0%, in prad_mich. Inactivating mutation adds 3 to 11% on top (182 of 2,260, 8.1%, in prostate_msk_2024; 46 of 424, 10.8%, in prad_mcspc_mskcc_2020). | cBioPortal (TCGA) |
| Triple-negative breast cancer | 12-35% | Mutation or deletion (loss) | PTEN mutation or loss in 35% of basal-like tumours, with INPP4B loss in 30% (Cancer Genome Atlas 2012); cBioPortal: deep deletion in 25 of 119, 21.0%, and mutation in 8 of 123, 6.5%, in brca_tcga_pan_can_atlas_2018; mutation in 18 of 299, 6.0%, and deep deletion in 16 of 320, 5.0%, in brca_metabric; mutation in 15 of 176, 8.5%, and deep deletion in 10 of 176, 5.7%, in breast_msk_2018. PTEN alterations (mutation or one- or two-copy deletion) in 29% of 62 metastatic TNBC patients treated with checkpoint inhibitors, where they went with a 6% versus 48% response rate (Barroso-Sousa 2020, Clin Cancer Res). | doi.org |
| Colorectal cancer | 6-8% | Inactivating mutation or deep deletion | cBioPortal: mutation in 446 of 7,237, 6.2%, plus deep deletion in 70, in crc_msk_2026; 68 of 1,134, 6.0%, plus 19 deletions, in crc_msk_2017; 34 of 534, 6.4%, plus 17 deletions of 592, in coadread_tcga_pan_can_atlas_2018; 51 of 619, 8.2%, in coadread_dfci_2016. PTEN mutation prevalence differs by side and by precise location (Loree 2018). | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
It separates two explanations that are usually run together. Some of the difference in prostate cancer outcomes by race is in the tumour genome and persists when access to the same centre is held constant, and some of it tracks with income rather than with ancestry, so equalising access alone would not eliminate the gap.
It is the prospective test of the PI3K and androgen receptor feedback hypothesis in men, and it shows both halves of the answer: the biomarker-selected population benefits, and the benefit is small enough that the toxicity has to be weighed honestly.
PAKT gives the trial-based prevalence of PI3K-pathway alteration in first-line metastatic TNBC (one in five) and the strongest signal for AKT inhibition in that subgroup; the phase 3 CAPItello-290 did not confirm it.
It splits the alterations into two groups with different practical meanings. The repair defects are present at diagnosis at close to their castration-resistant prevalence, so testing early is worthwhile; AR, TP53 and RB1 changes accumulate later, so a diagnostic sample does not answer questions about the disease in front of you at relapse.
PTEN loss, the most common PI3K-pathway lesion in TNBC, may mark primary immunotherapy resistance, and TMB may add to PD-L1 in choosing who gets checkpoint blockade.
What a prostate cancer sequencing report looks like in practice, and the numerical basis for two clinical rules: do not expect checkpoint immunotherapy to work unless the tumour is mismatch repair deficient, and do not treat a CDK12 alteration as if it were a BRCA alteration.
It is the caution attached to the sidedness rule: a tumour at the hepatic flexure and one at the caecum are both called right-sided and are not the same disease.
This is the sourced bridge between expression subtype and mutation: it tells a clinician that a LAR tumour is the one to sequence for PIK3CA and AKT1, and that immunomodulatory biology is a favourable prognostic group before any immunotherapy.
Query for this target: (TITLE:"PTEN" OR ABSTRACT:"PTEN" OR TITLE:"phosphatase and tensin homolog" OR ABSTRACT:"phosphatase and tensin homolog" OR TITLE:"MMAC1" OR ABSTRACT:"MMAC1" OR TITLE:"TEP1" OR ABSTRACT:"TEP1") 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 PTEN, not a curated reading list.
Shares Combined tumour suppressor defects characterise clinically defined aggressive variant prostate cancers, CIViC, HR-positive / HER2-negative breast cancer and the tag biomarker-parent.
Shares CIViC, IntOGen, Open Targets Platform, Prostate cancer and the tag biomarker-parent.
Shares CIViC, IntOGen, Open Targets Platform and the tag biomarker-parent.
Shares Glioma & glioblastoma, CIViC and the tag biomarker-parent.
Shares Endometrial cancer, Triple-negative breast cancer (TNBC), Colorectal cancer and the tag biomarker-parent.
Shares Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial, PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate, Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial, IPATential150: ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer.
Shares The clonal and mutational evolution spectrum of primary triple-negative breast cancers, Classifying colorectal cancer by tumor location rather than sidedness highlights a continuum in mutation profiles and consensus molecular subtypes, Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial, Reciprocal feedback regulation of PI3K and androgen receptor signalling in PTEN-deficient prostate cancer.
Shares Comprehensive molecular portraits of human breast tumours, Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis, Combined tumour suppressor defects characterise clinically defined aggressive variant prostate cancers, Concordance of circulating tumour DNA and matched metastatic tissue biopsy in prostate cancer.