Cancer stem cells therapies in clinical trials

By Mike Nagle


14/05/2007 - Specific stem cells are thought to be the origin of many, if not all, cancers and although there are several drugs in clinical trials, only small companies are currently conducting research in the area.

Cancer stem cells (CSCs) are thought to be the origin of at least eight different tumour types, according to Dr John Bates, who has recently penned a BioPharm report called 'Cancer Stem Cells: Emerging Therapeutic, Diagnostic and Market Opportunities'.

There are seventeen different companies and commercially focussed research groups that the report identified as developing molecules that either do, or could potentially, target CSCs. However, of those, only Genentech has the financial muscle to carry out a development programme to completion.

Bates told DrugResearcher.com that this emerging therapeutic target has "potentially massive implications in cancer therapy [but] seems to be being picked up only slowly by the pharmaceutical industry, despite recent huge advances in the area."

Bates went on to say that he thinks this will change as this emerging therapeutic class proves to be a "powerful new strategy that is highly complementary to existing therapies".

CSCs only represent one cell in every 1000 to 50000 rapidly dividing tumour cells. Scientists believe that these few hundred cells, which are found within the bulk of a tumour, are not only responsible for the formation and spread of cancer, but might also explain why tumours are resistance to many conventional therapies.

"Cancer stem cells have a wide range of in-built protection mechanisms which is thought to explain why some tumours are resistant to current therapies," said Bates.

This resistance might help explain why it is difficult to completely eradicate tumours and why the disease is frequently able to re-establish itself. Therefore, if these cells can be targeted specifically, pharma firms could plausibly develop fundamentally better therapies that could tackle the disease at its source, according to Bates.

These same properties also make CSCs a challenging target for drug developers, with scientists employing several different strategies in their research.

One strategy is to target the stem cells' niche environment. Bates explained that it is now thought that the CSCs leave the primary tumour early on to circulate around the body and establish themselves in an environment suitable for stem cells.

Genentech is developing a drug designed to interfere with cell communication systems - specifically, to inhibit the hedgehog pathway, which is thought to play an important role in the development of a number of cancers. The work is part of a collaboration with US pharma firm Curis and although not explicitly targeting cancer stem cells, this pathway could potentially affect them. The two companies announced the start of a Phase I clinical trial this year.

The recent isolation of CSCs has also allowed scientists to carry out gene analysis on the cells, with a view to using them in target finding, drug testing or in diagnosing the disease. Different cancer stem cells have different antigens on their surface, which could be used to specifically target CSCs in therapies.

ImmunoCellular Therapeutics has also revealed it is interested in CSCs. Last week, the company announced the beginning of a Phase I trial for its brain tumour vaccine last week. The vaccine is based on harvested dendritic immune cells that are then cultured with specific antigens found in tumours. The cells are then injected back into the patient, where they seek out tumour cells and mark them for destruction by the immune system.

However, ImmunoCellular Therapeutics has not indicated what the antigen target of the vaccine is and therefore, whether the immune therapy will specifically destroy CSCs or not.

Perhaps the most targeted therapy is being developed by Stemline Therapeutics. SL-401 is a biologic designed to target the Interleukin-3 receptor, which is overproduced on the surface of multiple cancers, including both leukaemia blast cells and leukaemia stem cells. The therapy is a recombinant protein attached to a toxin. Once SL-401 binds to the receptor, the toxin can get inside the cell and kill it. Currently in Phase I clinical trials, Stemline said SL-401 "has been shown to impair the ability of cancer stem cells to form tumours".

Geron, a US biopharma company, is also developing a drug that might kill CSCs. GRN163L is formed from DNA-like nucleotides that bind to the active site of an enzyme called telomerase and thus inhibit it. Telomerase is expressed in almost all cancer cells but not in normal cells but Bates explained that the extent of telomerase activity in stem cells is still unclear. The therapy is currently in Phase I clinical trials.
http://www.drugresearcher.com/news/ng.asp?n=76503-genentech-immunocellular-therapeutics-stemline-therapeutics-geron-cancer-stem-cells