New cancer drug looks promising in human trials
Initial human trials of a new Danish-American cancer drug reveal encouraging results.
A new cancer drug, known as G202, has been shown to exhibit positive effects against liver cancer in initial human trials.
In a experiments, the drug managed to significantly delay the development of new tumours in liver cancer patients who had not responded positively to other forms of cancer treatment.
The encouraging interim results bode well for the future of the revolutionary form of treatment for patients – including those with other forms of cancer – who doctors are struggling to cure today.
The new findings were recently published by the American biotech company GenSpera, which has teamed up with researchers from Copenhagen University in Denmark and Johns Hopkins University in the US.
Drug delays development of new tumours in liver cancer patients
If we can establish a sufficient life-prolonging effect for a sufficiently large group of patients, we will be ready to start the final large-scale experiments and hopefully make G202 a success in the treatment of cancer.
Professor Søren Brøgger Christensen
The promising results come from so-called phase 1 trials, which are actually only carried out to determine the right dose for patients, without them suffering serious side effects.
Phase-1 trials are usually carried out on healthy people, but when it comes to cancer medication, the subjects are typically cancer patients in the terminal phase.
In this trial of 28 cancer patients with various forms of cancer, the researchers discovered that liver cancer patients responded positively to treatment with the new drug.
Out of five patients with liver cancer, the G202 proliferation of tumours was arrested in three of the patients for up to 11 months, which is significantly longer than the two months it usually takes for this type of tumour to spread.
Thapsigargin, which was originally isolated from a Mediterranean plant in order to help scientists understand the skin-irritating effect of the resin, is a unique cytotoxin (cell poison), which binds closely to the SERCA calcium pump in cell membranes and blocks its function.
When SERCA is blocked, the cell cannot sustain the concentration of calcium in some intracellular calcium stores. Over the next 24 hours, this will cause the cell to trigger programmed cell death (apoptosis). In this way, thapsigargin can be used to make cancer cells commit suicide.
”This is great news and it has made oncologists really happy,” says one of the researchers behind the new drug, Professor Søren Brøgger Christensen, of the Department of Drug Design and Pharmacology, Natural Products Research, at the University of Copenhagen.
“Of course, trials with only five patients do not lead to scientifically valid conclusions, but it is nevertheless a very encouraging result that we managed to extend the life expectancy of cancer patients in the terminal phase.”
New drug only hits tumours
The new drug is developed from the natural substance thapsigargin, a so-called cytotoxin, or cell poison, which kills all the cells in the body.
By coupling thapsigargin to a larger molecule, the researchers obtained a compound, which the body's cells could not absorb.
It is this coupling of thapsigargin and the larger molecule that makes the new cancer drug unique.
Many cancers secrete a special enzyme inside in the blood vessels of the tumour. These include prostate cancer, liver cancer, kidney cancer and ovarian cancer. This enzyme only occurs to a limited extent in the prostata in the body. By liberating the cytotoxin in the blood vessels, the energy supply to the tumours is cut off and the tumour shrinks.
The enzyme is also the only one in our bodies that is capable of cleaving the bond between thapsigargin and the larger molecule, and is thus capable of releasing the toxin.
“The toxin will therefore only be activated in the blood vessels of the tumour and will only hit the tumours,” says Christensen.
Highly effective in mice trials
The new cancer drug has already been tested with great success on mice with various forms of cancerous tumours.
Here, the scientists first demonstrated that thapsigargin is only released in the tumours and does not affect cells elsewhere in the body.
Subsequent experiments also showed that mice that had been treated with the new drug experienced a 50-percent reduction in the size of their tumours over 30 days. For the mice that did not receive the drug, the tumours grew four-fold in size over the same 30-day period.
“It is this exact effect we would like to see and recreate in human cancer patients,” says the professor.
Phase-2 trials in progress
The natural follow-up to the positive results from tests with mice and humans is phase-2 trials with humans.
The researchers are about to start examining the effect of G202 on 28 patients with liver cancer. The results from this experiment are expected to be in by the end of 2014.
If these results show the same tendency as the phase-1 trials, we will be one step closer to seeing a new cancer drug on the market, says Christensen:
”If we can establish a sufficient life-prolonging effect for a sufficiently large group of patients, we will be ready to start the final large-scale experiments and hopefully make G202 a success in the treatment of cancer.”
Translated by: Dann Vinther
- "A First-in-Human, Phase I Clinical Study of the Safety, Tolerability and Pharmacokinetics (PK) of G-202, a Thapsigargin-Based PSMA-Activated Prodrug, in Patients with Advanced Solid Tumors", www.genspera.com