As of June 2021, 31 projects have been funded by the Foundation and its forerunner organisation, including 18 currently active projects. A total of more than £13 million in funding has been provided for research with individual funding in the range of £10,000 – £1,000,000+, and we are actively seeking new funding applications.
On this page is a summary of our current projects with links to case studies, and a list of publications.
Type of study: Interventional clinical trial.
Description: Phase I/II 6-month, randomized, double-blind placebo-controlled trial of everolimus in individuals, ages 5 to 45 years with a PTEN mutation, with safety and neurocognition as the primary endpoints. NCT02991807
Type of study: Interventional clinical trial
Description: Phase II, 1-year, open-label, pilot, study to examine the effects of sirolimus on colon polyp burden in Cowden syndrome. NCT04094675
Adapting and refining existing neurobehavioural instruments for use in the PHTS population.
Type of study: Pre-clinical – PHTS model and translational
Description: Develop models of vascular malformation associated with PHTS to better understand their pathobiology and the contribution of various signalling molecules/pathways, and to test potential therapeutics.
Type of study: Pre-clinical – translational
Description: Assess the ability of potential therapeutics targeting the various nodes of the PI3K pathway to prevent cancer development in pre-clinical models of PHTS
Type of study: Pre-clinical – PHTS model
Description: Generate patient-derived iPSC lines to support future research on treatments.
Type of study: Pre-clinical – translational
Description: Repurposing studies focused on testing small molecule inhibitors of the PI3K pathway in pre-clinical models of PHTS vascular malformations, tissue overgrowth and oncology.
Description: Validation, using pre-clinical models of PHTS, of a novel target as a potential novel therapeutic strategy for PHTS.
Type of study: Pre-clinical - PHTS model
Description: Develop and characterise a novel pre-clinical model of PTEN loss in the brain for testing of potential therapeutics.
Type of research: Basic research
Description: Characterise a series of PTEN antibodies to develop new research tools to better define and understand the biology and function of PTEN
Listed here are publications that are associated with the projects identified above, or for related activities in which PTEN Research (or its forerunner organisation) have been acknowledged.
Antonio Y Hardan, Booil Jo, Thomas W Frazier et al. A randomized double-blind controlled trial of everolimus in individuals with PTEN mutations: Study design and statistical considerations. Contemp Clin Trials Commun. 2021 Volume 21, March 2021, 100733
Thomas W Frazier, Ritika Jaini, Robyn M Busch Mol et al. Cross-level analysis of molecular and neurobehavioral function in a prospective series of patients with germline heterozygous PTEN mutations with and without autism. Autism 2021 12:5.
Busch RM, Srivastava S, Hogue O et al. Neurobehavioral phenotype of autism spectrum disorder associated with germline heterozygous mutations in PTEN. Transl Psychiatry.2019, 9:253
Uljarevic M, Frazier TW, Rached G et al. Brief Report: Role of Parent-Reported Executive Functioning and Anxiety in Insistence on Sameness in Individuals with Germline PTEN Mutations. J Autism Dev Disord.2021 Feb 17 https://doi.org/10.1007/s10803-021-04881-5
Hendricks LAJ, Hoogerbrugge N, Schuurs-Hoeijmakers JHM, Vos JR. A review on age-related cancer risks in PTEN hamartoma tumor syndrome. Clin Genet.2021 99(2):219-225
Tischowitz M, Colas C, Pouwels S et al. Cancer Surveillance Guideline for individuals with PTEN hamartoma tumour syndrome. Eur J Hum Genet 2020 28(10):1387-1393
Yehia L, Eng C. PTEN hamartoma tumour syndrome: what happens when there is no PTEN germline mutation? Hum Mol Genet. 2020 Oct 20;29(R2):R150-R157. doi: 10.1093/hmg/ddaa127
Mighell TL, Thacker S, Fombonne E et al. An Integrated Deep-Mutational-Scanning Approach Provides Clinical Insights on PTEN Genotype-Phenotype Relationships. Am J Hum Genet. 2020 Jun 4;106(6):818-829
Yehia L, Seyfi M, Niestroj L et al. Copy Number Variation and Clinical Outcomes in Patients With Germline PTEN Mutations. JAMA Netw Open. 2020 Jan 3;3(1):e1920415. doi: 10.1001/jamanetworkopen.2019.20415.
Yehia L, Ngeow J, Eng C. PTEN-opathies: from biological insights to evidence-based precision medicine. Clin Invest. 2019 Feb 1;129(2):452-464. doi: 10.1172/JCI121277.
Novelli G, Novelli A, Borgiani P et al. WWP1 germline variants are associated with normocephalic autism spectrum disorder. Cell Death Dis. 2020 Jul 23;11(7):529. doi: 10.1038/s41419-020-2681-z.
Alvarez-Garcia V, Tawil Y, Wise HM, Leslie NR. Mechanisms of PTEN loss in cancer: It's all about diversity. Semin Cancer Biol. 2019 Dec;59:66-79. doi: 0.1016/j.semcancer.2019.02.001
Yehia L, Eng C. PTEN Hamartoma Tumor Syndrome. Gene Reviews 2021 NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK1488/
Jia M, Sangwan N, Tzeng A, Eng C. Interplay Between Class II HLA Genotypes and the Microbiome and Immune Phenotypes in Individuals With PTEN Hamartoma Tumor Syndrome. JCO Precision Oncology February 9 2021; 5:357-369. https://doi.org/10.1200/PO.20.00374
Kaymakcalan H et al. Prevalence and clinical/molecular characteristics of PTEN mutations in Turkish children with autism spectrum disorders and macrocephaly. Molecular Genetics & Genomic Medicine July 16 2021; 00:e1739. https://doi.org/10.1002/mgg3.1739