New Cancer Treatment
DRS IAN & LYNNE HAMPSON
SEPTEMBER 2013 – AN EXCITING NEW PROJECT STARTS AT
PROJECT TITLE: An invitro and in silicoinvestigation of a new class of cell behaviour modifying compounds for the treatment of cancer
PROJECT TIMESCALE: 2 years – 1st September 2013 to 31st August 2015
RESEARCHER: Dr Anthony Oliver
Lay Title: An investigation of the potential of a new class of cell behaviour modifying compounds for the treatment of cancer
Current non-surgical cancer therapies mainly fall into two categories: (a) Non-specific DNA damaging modalities such as radiation or chemotherapeutic agents (eg Platinum, cyclophosphamide etc); (b) Target-specific, non-DNA damaging agents such as kinase inhibitor drugs (eg Gleevec). Since the former are not cancer-specific, they produce the well known sequelae of sickness, hair loss etc. The latter is more cancer specific but typically tumours can adapt to become resistant to this type of targeted therapy.
Non-specific treatments have proved to be the mainstay of cancer treatment for many years since they are a catch all! What is not so widely known is that this type of treatment actually causes more DNA damage which means that any surviving cancer cells have greater genetic variability. This enables rapid evolution of therapy resistance in the surviving tumour cells which is actually enhanced by the treatment. The awful paradox is that the most successful treatments currently in use today, actually stimulate the acquisition of therapy resistance in recurrent disease. It is a bit like treating bacteria with a sub-lethal dose of antibiotics – resistant bacteria will quickly emerge. What is needed is a step change in cancer therapy which explores new therapeutic approaches to this disease.
Several years ago we identified a novel class of chemicals which do not kill either normal or cancer cells when these are grown separately in the laboratory. However, when the normal cells are mixed with the cancer cells and treated with the chemicals the latter go back to behaving like normal cells. Most surprising was that this effect persisted even after the chemicals were removed from the cultures and we proposed that the normal cells were reasserting growth control over the cancer cells. It is important to realise that they do not actually kill the cancer cells but merely alter their behaviour to that of normal cells. As a consequence, unlike the previously discussed non-specific therapies, these chemicals should not stimulate the rapid evolution of th
SEPTEMBER 2013 UPDATE – OVARIAN CANCER BIOMARKER DISCOVERY
Ovarian cancer currently affects more than 6,500 women in the UK each year and, like all cancers, the earlier it is detected the better the chance of survival. However, due to a combination of the location of the ovaries deep within the body and the symptoms it produces ovarian cancer can often be misdiagnosed as irritable bowel or pre-menstrual syndrome. As a result, it is unfortunately quite common that ovarian cancers are usually diagnosed at an advanced stage, where available treatment options will have limited success.
While some common cancers, for example cervical cancer, have a distinct and therefore preventable cause, very little is known about the causes of ovarian cancer. While there are certain risk factors that may increase a woman’s risk of developing ovarian cancer, such as a prior family history, it is still thought that there may be a specific, as yet unknown, cause.
Whenever we are exposed to a pathogen, such as a virus or bacteria, our immune system produces antibodies which are small defence proteins that are able to fight off that specific infection and return us to health. Every pathogen results in a distinct antibody that will only recognise that specific pathogen. In order to provide life long protection our bodies maintain a supply of these specific antibodies that lie dormant until needed such that if we encounter the same pathogen in the future, they can provide a quicker, more efficient response.
Antibodies are therefore a snapshot of every infection, germ & pathogen you have ever been exposed to since birth!
We propose to compare the antibody repertoire of normal, disease-free women to those with ovarian cancer. In this way we may be able to identify antibodies against unknown pathogens that are present in the samples from ovarian cancer patients which are absent in normal control women. It is hoped this may provide clues to the cause of ovarian cancer. If we can identify these antibodies and their respective pathogens, it may be possible to design a screening procedure, much like those in place for prostate and cervical cancers, that will identify ovarian cancers at a much earlier, less-advanced stage which should improve the chances of survival.
However, the range of antibodies in an adult human, each recognising a distinct pathogen, can number in the billions, and this will vary depending on which pathogens they have been exposed to during their life. Consequently, using classical laboratory techniques for studying antibodies, such as bacterial peptide display libraries, it would take us a lifetime to search through this complex antibody mixture!
We are therefore attempting to combine a technique called bacterial peptide display libraries, with a new state of the art molecular biology technique known as Next Generation Sequencing or NGS. NGS is a new technology that allows us to sequence DNA on a scale never seen before. Using NGS, a single researcher can generate as much DNA sequence data in a matter of hours that, up until recently, took hundreds of scientists and more than 10 years to produce!
Due to the extremely specific way in which antibodies bind to pathogens, if we can identify which antibody we have detected, by comparing the DNA sequences generated by NGS with a global database of known DNA signatures, we can identify the pathogen that caused that antibody to be produced.
We speculate that specific antibodies found in women with ovarian cancer will be not be present in disease-free women and one of these ‘different’ antibodies may be the result of a previously unknown infectious cause of ovarian cancer!
Clearly, if this approach is successful it could not only lead to improved diagnostics but may also lead to novel prevention strategies that are aimed at preventing the infection and thus the cancer.