Rapamycin treatment for a child with germline PTEN mutation

  title={Rapamycin treatment for a child with germline PTEN mutation},
  author={Deborah J. Marsh and Toby N. Trahair and Janet L Martin and Wey Yeeng Chee and Jan Walker and Edwin P. Kirk and Robert C. Baxter and Glenn M. Marshall},
  journal={Nature Clinical Practice Oncology},
Background A 9-month-old boy with Proteus syndrome and a de novo germline mutation in the tumor suppressor PTEN was referred to a specialist centre for management. Over the first years of life, the patient developed life-threatening respiratory dysfunction and malnutrition because of progressive growth of hamartomas affecting the chest, mediastinum, abdomen and pelvis.Investigations Physical examination, CT scans of the mediastinum, pelvis and abdomen, measurement of serum insulin-like growth… 
Oral rapamycin in the treatment of patients with hamartoma syndromes and PTEN mutation
A 6‐year‐old male with progressive loss of function of left hand and forearm associated with pain was treated with oral rapamycin and regained pain‐free full mobility.
PTEN hamartoma tumor syndrome in childhood and adolescence—a comprehensive review and presentation of the German pediatric guideline
Affected families frequently experience a long way until the correct diagnosis for their child’s peculiarity is made, and the presented screening recommendation should be revised regularly according to the current state of knowledge.
Sirolimus treatment of severe PTEN hamartoma tumor syndrome: case report and in vitro studies
In vitro findings point to PI3K and AKT inhibitors as potential treatment options for patients with severe forms of PHTS, and sirolimus treatment led to an improvement of the patient’s clinical status and a transient reduction of the thymus.
PTEN hamartoma tumor syndromes
Improved understanding of the biology of PTEN and the PI3K/Akt/mTOR pathway means inhibitors of this pathway are being developed as anticancer agents and could have applications for patients with PHTS, for whom no medical options currently exist.
Toward Systems Pathology for PTEN Diagnostics.
The prospect of moving toward a systems pathology approach for PTEN diagnostics is discussed, incorporating clinical and molecular pathology data with the goal of improving the clinical management of patients with a PTEN mutation.
Successful Treatment of Juvenile Polyposis of Infancy With Sirolimus
Soon after initiation of treatment with sirolimus, blood and albumin infusions were no longer needed and resulted in improved patient growth and quality of life and this case represents the first detailed report of successful drug therapy for life-threatening juvenile polyposis of infancy.
Exceptional Response to AKT Inhibition in Patients With Breast Cancer and Germline PTEN Mutations
Cowden syndrome is an autosomal dominant genetic disease with an estimated incidence of one in 200,000. Affected individuals develop multiple systemic hamartomas and have a cumulative lifetime risk
Treatment strategies for mosaic overgrowth syndromes of the PI3K-AKT-mTOR pathway.
This review aims to describe the clinical and molecular characteristics of the main OS involving the PI3K-AKT-mTOR pathway, along with the treatments available or under development, and summarizes available data regarding OS.
Infantile Lhermitte-Duclos Disease Treated Successfully With Rapamycin
Repeat magnetic resonance imaging (MRI) reveals lack of brainstem compression or distortion of pituitary stalk, andRapamycin should be considered in cases of Lhermitte-Duclos disease where surgical removal may not be an option, as in this case where the cerebellum was entirely involved.


Germline mutation of the tumour suppressor PTEN in Proteus syndrome
Clinical overlap exists between PS and another hamartoma syndrome, Bannayan-Riley-Ruvalcaba syndrome, in which up to 60% of affected subjects are known to carry a germline mutation of the tumour suppressor gene PTEN .6 BRR also shows partial clinical overlap with Cowden syndrome.
Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation.
There appeared to be an interdependent association between mutations upstream and within the PTPase core motif, the core motif containing the majority of missense mutations, and the involvement of all major organ systems (central nervous system, thyroid, breast, skin and gastrointestinal tract).
Rapamycin causes regression of astrocytomas in tuberous sclerosis complex
This work sought to see whether therapy with oral rapamycin could affect growth or induce regression in astrocytomas associated with TSC.
Cancer phenomics: RET and PTEN as illustrative models
The phenomic characterization of PTEN and RET underscores the importance of incorporating robust phenomics into the host 'omic' profile, and shows that the evolution of phenomics will be crucial to the advancement of personalized medicine.
Proteus syndrome: diagnostic criteria, differential diagnosis, and patient evaluation.
This is a review of recommendations for diagnostic criteria, differential diagnosis, and guidelines for the evaluation of patients on Proteus syndrome held in March 1998 at the National Institutes of Health.
Hemangiomas in children.
Hemangiomas are the most common soft-tissue tumors of infancy, occurring in approximately 5 to 10 percent of one-year-old children, and new therapeutic approaches, such as treatment with interferon and lasers, have altered understanding of this common childhood problem and the way the authors approach it.
Pilot study of the combination of EGFR and mTOR inhibitors in recurrent malignant gliomas
Twenty-eight heavily pretreated patients with recurrent malignant gliomas were administered EGFR inhibitors (gefitinib or erlotinib) in combination with the mTOR (mammalian target of rapamycin) inhibitor sirolimus, and the regimens were reasonably well tolerated.
Cancer drugs to treat birth defects
  • A. Wilkie
  • Biology, Medicine
    Nature Genetics
  • 2007
The demonstration of activated RAS-ERK signaling in a mouse model of Apert syndrome suggests that drugs designed to inhibit this pathway in cancer may also delay the progression of several serious pediatric syndromes.
Rapamycin blocks tumor progression: unlinking immunosuppression from antitumor efficacy1
It is suggested that rapamycin may be of value for the management of posttransplant malignancy through a cell-autonomous and host-immunity independent mechanism for cyclosporine-associated tumor progression.