Aspirin as an anti-metastatic drug - in 1977

Working on drug repurposing often involves an element of historical research. Drugs like cimetidine, nitroglycerin and propranolol have been around for decades and there’s a lot of good data that we can extract from old articles, clinical trials and retrospective studies. One of the best known examples of old drugs is aspirin - which is attracting a huge amount of attention from clinical researchers in oncology. There is a huge literature on aspirin, with much more on the way as clinical trials are designed, run and reported.

One of the most intriguing things about aspirin is the data that suggests that it might work as an anti-metastatic agent. There is data that shows that aspirin may be effective in reducing the risk of metastatic spread in breast, prostate and colon cancer (for example this recent meta-analysis reported a relative risk of metastasis of 0.77 with aspirin).

That we’ve known about the anti-cancer potential of aspirin for a long time isn’t a surprise – but I have to admit to being surprised to come across a paper from 1977 arguing the case that aspirin might be an effective anti-metastatic drug. The paper is Aspirin for reducing cancer metastases? by Henschke, Luande and Choppala (J Natl Med Assoc. 1977 Aug;69(8):581-4). The paper is available open access (here), and while the data is old, the arguments it makes are still vital and relevant. It really begs the question, how is that things haven’t moved forward more quickly? And, more crucially, how can we make sure that things move forward more quickly in the future. Not just for aspirin but for so many of the other old drugs that have good data in their favour.

Innovative new brain tumour trial kicks off

The Anticancer Fund is pleased to announce that on Tuesday 15th November 2016, the first patient was enrolled in a clinical trial called CUSP9v3 for recurrent glioblastoma at the Department of Neurosurgery, University Hospital of Ulm, Germany. This is a phase 1 clinical trial. The study treatment will be given to 10 patients to assess safety and tolerability.

Glioblastoma is the most frequent type of malignant brain tumour in adults. In Europe and North America, there are 3-4 new cases per 100,000 inhabitants per year. Even when all visible tumour is surgically removed, glioblastoma almost always returns within a year. Therefore, after surgery patients are treated with radiotherapy and chemotherapy. Despite this additional treatment, glioblastomas usually regrow and at some point can no longer be effectively treated, often resulting in death 1-2 years after the initial diagnosis.

 "For decades, researchers have been looking for new experimental therapies for our patients with no real success yet" says Professor Marc-Eric Halatsch, the neurosurgeon leading the trial. "Together with Dr Richard Kast (USA), we sought to address the problem that glioblastomas usually find a way to escape the action of a single drug. In 2013, we teamed up with an international group of researchers to propose a treatment that would act on multiple mechanisms used by glioblastoma cells to grow. This treatment consists of 9 drugs that are currently on the market for other indications than cancer (‘repurposed’ drugs). These nine drugs have ancillary attributes that block several of the mechanisms glioblastoma cells use to grow. These drugs had remarkable effects in preventing growth of glioblastoma cells in preclinical studies. A clinical trial was warranted."

In addition to contributing to the design and set-up of the trial, the Anticancer Fund will provide €300,000 for this study. "This type of treatment is not developed by the pharma industry because the 9 drugs are from different companies and all are off-patent and mostly available as generics" says Lydie Meheus, director of the Anticancer Fund. "This implies that the treatment, if successful, will not generate substantial additional financial return for the manufacturers of the drugs. Since the treatment can benefit patients and the healthcare system, it must be developed with the support of philanthropy and governments."

Patients participating in the trial will receive CUSP9v3 for one year. When all patients have completed 2 months of treatment, a first analysis will be done on the safety and tolerability of the combined treatment.

If the combination is well tolerated, a larger multi-centre study will be initiated to evaluate the treatment’s efficacy.

Further information on the CUSP9v3 trial can be found on www.anticancerfund.org or on www.clinicaltrials.gov (NCT02770378).

Guest Post - Crowdfunding for Pediatric Cancers

Cesare Spadoni, founder of aPODD (accelerate Paediatric Oncology Drug Development), talks to Pan Pantziarka about the problems in drug development in children's cancers, and about the crowdfunding campaign to find a new treatment for Medulloblastoma.

Pan: What is the aPODD foundation aiming to do?
Cesare: aPODD (accelerate Paediatric Oncology Drug Development) was set up with the mission to speed up the development of better and safer treatments for children with cancer. This is a cause that is very close to my heart. I lost my first daughter to cancer a few years ago. That is when I began thinking about doing something for children with cancer.

Obviously, you can have a positive impact on sick children and their families in many different ways. In my case, because of my professional background in drug development, I felt compelled to do something to address the major problem preventing any further clinical improvement for children and adolescents with cancer: the lack of therapeutic options and the delayed access to the most innovative treatments.

Specific anti-cancer drugs are not developed for younger patients because it is not profitable for industry to do so. This is an area where patients’ organisations may play a vital role. Drug repurposing is certainly an area we are very much interested in. By looking at existing drugs we may be in a position to identify possible new treatments much faster and at a fraction of the cost and risk of new drug development

Pan: How is this campaign different to others?
Cesare: We are looking to identify a potential new treatment for Medulloblastoma, a rather aggressive form of brain cancer that is more frequent in children and adolescents. The current therapeutic options for this cancer are limited and very harsh, including high dose chemotherapy and radiotherapy. The impact on patients may be devastating as the lucky survivors may face severe health problems later in life.

For this project we are partnering with Healx, a company based in Cambridge (UK), which offers very advanced technologies and strong expertise in drug re-purposing. Healx is applying advanced computational biology tools, data analytics and machine learning to make sense of complex biological data sets and match those with the profiles of known drugs.

We are now in the process of finalising a list of drugs that we would like to test experimentally in Medulloblastoma cell lines in view of progressing further with the most promising ones.
We are very excited by these early results and we are really hope that this crowdfunding is successful so that we can proceed as fast as we can.