Scientific strategy

Our Mission

Our mission is to fund research that will lead to treatments for PHTS.

We hope to develop a therapy with the potential to transform people’s lives within the next ten years. The pursuit of this goal will also lead to improvements in the care of people with PHTS.

To achieve this, we will fund clinical trials in PHTS patients, as well as other clinical, translational and basic research to compare drugs, test key concepts and collect patient data to support clinical efforts.

Timeframe

1-2 years: Generate evidence to refine the selection of the most appropriate therapies to develop further for PHTS.

2-5 years: Generate evidence of efficacy and utility of a therapy, or therapies, that demonstrates a meaningful benefit to PHTS patients.

5-10 years: Focus on getting a clinically approved and available therapy for as many PHTS patients as possible.

Beyond: Assess the impact of clinically approved therapies on the cancer risk in PHTS patients.

Our focus

The non-malignant symptoms of PHTS

The increased lifetime risk of cancer is one of the key concerns for people with PHTS. However, primary cancer prevention is not a realistic indication to pursue for PHTS. Therefore, our focus is on developing therapy options to treat non-malignant symptoms with clinically measurable endpoints. Results from a patient survey on unmet need will be used to guide therapy development.

Given the shared genetic aetiology of PHTS, it is hoped that efficacy of a targeted therapy against a given manifestation will translate across to other symptoms. Although there are many different types of PTEN mutation that can give rise to PHTS, we will develop therapies that will benefit all PHTS patients independent of their mutation type.

Drugs that can normalise the PI3K signalling pathway

Our aim is to find a therapy that can fix abnormal signalling caused by a PTEN mutation, providing clinical benefit to patients. The molecular function of PTEN, as an enzyme that restricts the activity of a group of key growth-promoting enzymes called phosphoinositide 3-kinases (PI3Ks), is well established. Encouragingly, evidence from PHTS patients and animal models has linked many PHTS symptoms to hyper-activation of the PI3K pathway. Our efforts will therefore concentrate on targeting this pathway.

We will begin by testing a class of drugs known as the rapalogs (sirolimus and its analogue everolimus). This is because clinical and preclinical evidence suggests that the target of rapalogs, mTOR, contributes significantly to the pathology of PHTS. What’s more, in contrast to most drugs targeting the PI3K pathway, rapalogs have already been licensed for the treatment of certain cancers as well as some rare diseases. As a result, there is data available on their safety and efficacy. Alongside these efforts, we will also explore the utility of alternative agents that target the PI3K pathway.  

Small molecules

Our efforts are primarily aimed at assessing small molecule drugs that could be used to treat symptoms of PHTS. However, other therapeutic approaches, such as biologics, may also warrant exploration.

Our strategic priorities

Over the next five years, we want to make significant advances in the areas described below.

Clinically test therapies to treat PHTS

We will assess the efficacy and safety of rapalogs as treatment options for specific symptoms of PHTS that can bring meaningful benefit to patients.

We are already supporting two clinical trials exploring the use of rapalogs in people with PHTS. Going forward, we will support further clinical research on the utility and safety of rapalogs in PHTS. We will also undertake translational research needed to inform further clinical trials in this drug class.

Identify new therapy options for PHTS

We aim to identify other agents beyond rapalogs as treatment options for PHTS.

We will fund research to identify and/or validate cellular drug targets for PHTS with the aim of generating evidence to justify future clinical testing. This includes examining the relationship between drug targets and different PHTS symptoms, and the development of in vitro and in vivo models of PHTS. We will explore molecules known to inhibit the PI3K pathway as well as completely novel targets.

Improve outcomes for people with PHTS who develop cancer

We will improve understanding of the risk of cancer in PHTS, improve early detection, and also research how those with PHTS who develop cancer respond to currently available cancer treatments.

We will support research that leads to a better understanding of the risk of cancer in PHTS patients. We will collect and analyse data on the outcomes of PHTS patients, should they develop cancer, to improve clinical management guidelines and care, and ultimately improve patient outcomes. We will also explore new methods to improve early screening and detection of cancer in PHTS patients to enable faster diagnosis and treatment.

Improve the understanding of PHTS

We will address key unknowns of PHTS relating to its biology, complete clinical spectrum, epidemiology and the unmet need of patients.

We have commissioned a survey of patients to help us understand their unmet needs. We will fund the analysis of existing and newly collected patient data, as well as support the wider PHTS research community to do the same. We will support the initiation of PHTS patient registries in places where none exist, starting with the creation of a UK PHTS registry. To make sure that the field can make most use of the data stored in different registries, we will help support the development of data collection guidelines so that it is gathered in a systematic way.

 

How we will achieve this

We will fund scientific research through specific calls that align with our strategic priorities. For more details on the funding mechanisms and dates see Apply for Funding.

We are also open to collaborating and building strategic partnerships with both academic and industry partners to enable us to progress faster. If you are interested in working with us please get in touch by emailing us at research@ptenresearch.org

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