The Salford Viewpoint: Complex sugar molecules may be the key to safer chemo
The ability to aim chemotherapy drugs at cancer cells - and just cancer cells - has been a goal for medical researchers for a long time. So is the recent discovery of a malaria proteinthat appears to target the tumour and not the patient’s normal cells a significant step forward in the arms race against cancer?
Certainly the idea of targeting cancer cells with proteins that carry a toxic drug payload is not new. In fact, several of these “protein-drug complexes” have been approved by the US Food and Drug Administration since 2011. Perhaps the most important difference between this latest discovery and the available protein-drug complexes is the target: a complex sugar molecule that is mainly found on cancer cells or the placenta of pregnant women and is largely absent in other normal human cells.
Helpful malaria parasite
The origin of the protein that binds to these sugars, in this case from the malaria parasite, may make big headlines but its source is largely irrelevant. It is the ability of a protein to distinguish between cancer cells and normal cells that will largely determine its fate as a drug delivery mechanism.
The ultimate goal of cancer drug discovery has always been linked to the ability to discriminate between normal and cancerous tissue. The ability of a drug to kill cancer cells and not normal cells would minimise the toxic side effects associated with traditional chemotherapy and allow higher doses to be used to speed up the destruction of the tumour.
Proteins can be used to home in on a target on the surface of cancer cells and deliver a drug-laden warhead. This requires a target on the surface of the cancer cells that isn’t present on normal tissue. Scientists have been searching for these targets for many years and many so-called targeted cancer treatments have been developed, with varying degrees of success.
The idea that one such cancer target might be found in the placenta of pregnant women, as is the case for this latest discovery, may seem at first glance to be rather bizarre. However, researchers have believed for many years that the secrets associated with the initiation and progression of cancer, may be hidden in the way that the foetus develops from a simple pre-embryonic clump of cells and the changes that occur in the placenta during the baby’s development in the womb.
Understanding some of these normal development processes might lead to a groundbreaking discovery in cancer research, such as has been reported by these researchers. In this instance, the protein found on the surface of the malaria parasite was found to bind to targets on the placenta. This allowed the parasite to associate itself with the placenta, which can lead to a common complication of malaria infection in pregnancy. But the subsequent discovery that it also binds to specific sugar targets on the surface of cancer cells was exploited by the scientists.
Sugar carries important information
Although largely neglected by the scientific community, over many years, complex sugars are rapidly being seen as some of the most important molecules on the surface of normal and cancerous cells. In many ways the information carried by sugars is far more complex than that carried in the DNA of your genes. And perhaps the most important advance in this new study is really the sugar target itself.
Previous attempts to use complex sugars as a target for cancer treatment have had been encouraging, however, most of these have involved work in cancer vaccines. So the identification of proteins that can seek out sugars only found on the surface of cancer cells could be a major step forward in our ability to target cancer with protein-drug complexes.
So will this new “protein guided” drug delivery system really deliver cancer drugs to human tumours and minimise the risk of damage to the patient’s healthy tissue? Evidence from an experiment with mice suggests that it will. Unfortunately, experiments on animals do not always translate into the successful treatment of patients, and we must be cautious in interpreting these kinds of findings. The number of different sugar structures on the surface of normal and cancerous cells is also vast and small differences can lead to their success or failure as a cancer-specific target. A relatively insignificant change in the structure of the sugars between the non-human models and patients could easily lead to the protein drug complex hitting normal cells as well as the cancer, causing considerable harm to the patient.
Although the results of this recent study are exciting, it will be a long time before we can determine its full impact on the field of targeted cancer treatment. Scientists and people with cancer will undoubtedly watch with great interest as these protein-drug complexes move into clinical trials.
*Image by NIAID