Coordinated Attack to the Signalling Paths of Glioblastoma

10 December 2020 12 By Roberto Pugliese

As I told you we are working intensively on the development of a new version of the chatbot however when I came across this news I decided immediately to write an article. This is a new CUSP-ND project that aims to fund a clinical trial similar to CUSP9v3, proposed by the Anti Cancer Alliance ( for patients with recurrent glioblastoma, this time on newly diagnosed patients. This is the video that explains the basic idea and the rationale behind it.

The video is in English, so I decided to report the basic steps below in order to improve the readability. High-grade gliomas kill more children than leukemia, more women than breast cancer, and younger men from testicular cancer, but because the patient population is relatively small compared to that of more common cancers, there is no economic incentive sufficient to push the development of new treatments. As a result, median overall survival has improved little over the past 30 years, going only 8 to 15 months after diagnosis.

If we were to receive a diagnosis of glioblastoma today we would necessarily have to prepare to die since the standard treatments available are not capable of saving life except in very rare lucky cases. We would therefore try to try experimental treatments which, however, only become available when standard treatments have failed. The question is therefore whether we have to wait for a treatment to fail before having access to experimental therapies, when one knows from the beginning that sooner or later the standard treatment will fail.

The history of cancer teaches us that when doctors and patients work together, great results can be achieved. CUSP-ND is a project that arises from an international collaboration of doctors, researchers, patients and long-term survivors who share the desire to offer patients who are suffering from glioblastoma today, better treatment opportunities. The group was formed after the release of the Surviving Terminal Cancer movie which tells the story of 3 patients who defeated glioblastoma through a radical treatment strategy that used the off-label drug cocktail approach. The research is led by Prof. Dr. Marc-Eric Halatsch of the University of Ulm in Germany who has already successfully participated in the CUSP9v3 clinical trial. It is believed that using the same approach on new diagnoses the results can be even better. The Standard of Care for glioblastoma patients is notoriously palliative. One of the hallmarks of tumors in general and of glioblastoma multiforme in particular is the development of cellular resistance that cannot be adequately managed by treatments that involve the use of a single drug. When the cancer is in its infancy, a single drug such as Temozolomide can achieve some results but, as the cancer develops, new mutations arise that complicate treatments. A single drug can achieve some results and eliminate a significant number of cancer cells. The problem lies in the cells that survive that develop rapidly and in each new generation develop better survival mechanisms that allow them to resist the treatments carried out through the same drugs they have learned to recognize.

The sequential treatment mechanism, therefore, even if in the initial phase may show some efficacy, is counterproductive in the long term. Administering several drugs in sequence does not allow to exploit the window of opportunity represented by the damage produced by the single treatment on which other treatments could leverage. The idea of ​​the CUSP-ND project is to use off-label drugs available on the market that have an effect on some signalling paths of glioblastoma. Using them in parallel they can be much more effective both in producing damage to the glioblastoma and against the development of resistance to individual drugs. When a drug blocks a glioblastoma growth path it uses the other pathways not yet blocked. By blocking in parallel as many growth paths as possible, the Standard of Care can also be made more effective. The CUSP-ND project aims to carry out a real clinical trial to evaluate the real effectiveness of this line of treatment by adding a cocktail of off-label drugs to the Standard of Care.

In fact, even though the STUPP protocol, representing the Standard of Care, is the best known therapy, it is clear that it is not saving patients’ lives!