The BHD Literature Database has been updated with one paper:

Clinical research:

Wagle et al. (2014) describe the case of a 57 year old woman with anaplastic thyroid cancer, which has a median survival time of five months. Following thyroidectomy, lymph node resection and chemotherapy, the patient was enrolled on a phase II trial of everolimus. The patient has a sustained response to treatment for 18 months, at which point her tumour became resistant to everolimus. This patient was the only patient on the trial to show any response to everolimus. Whole exome sequencing of germline, pretreatment, and resistant tumour DNA revealed that the pretreatment tumour had somatic inactivating mutations in TSC2, TP53 and FLCN, which likely lead to increased mTOR signaling in tumour cell, making the tumour particularly sensitive to treatment with mTOR inhibitiors. The resistant tumour had developed a missense mutation (MTOR^F2108L) in the FRB domain of mTOR, which prevents everolimus binding. In vitro studies show that MTOR^F2108L is still sensitive to kinase inhibitors, such as Torin1, suggesting that kinase inhibiton may be a suitable follow up treatment for this patient. The authors suggest that sequencing tumour DNA before and during treatment may suggest the most effective treatment regimen for the patient.

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