May 7, 2009
Cancer gene therapy
I have just attended an international cancer conference in Beijing and to my amazement and delight, what I once thought was impossible is happening right now. Sure as night follows day, in one meeting after another, there is increasing evidence that there is value in customising therapy based on the molecular genetics of a cancer.
That is, each patient should have treatment that is tailor-made for him, based on the molecular genetics of his cancer. I would never have believed it could happen.
Back in 1986, when I made up my mind to pursue further training in medical oncology, the use of chemotherapy in cancer treatment was quite archaic. There were very few drugs and, basically, we combined them in cocktails on a trial-and-error basis to see what worked and what did not.
Not long ago, all that mattered in a breast cancer case was the age of the patient, her menopausal status, the size of the tumour and the number of lymph nodes involved.
Then, we began to understand the importance of 'hormone receptor status" - that is, whether the cancer cells carried oestrogen and progesterone receptors. Even then, it was a fairly straightforward journey - for those with hormone receptors, hormonal therapy could be used either as an alternative treatment or in addition to chemotherapy.
Today, after decades of research into the molecular genetics of breast cancer, scientists have now identified the cancer genes responsible for promoting its growth, the most important of which is HER2-neu, also called c-erbB2.
This has helped to identify the breast cancers which tended to be more aggressive and resistant to therapy. The development of an antibody against this cancer gene, trastuzumab (better known as Herceptin), has revolutionalised treatment of breast cancer in patients whose tumours carried this gene.
Initially used in patients with metastatic (where cancerous cells have spread to other part of the body) breast cancer, Herceptin has proven to be useful in improving cure rates in those who have undergone surgery for early breast cancer.
Patients with breast cancers less than 1cm in size with no lymph nodes involved are considered as having very early stage disease. After surgery, these patients are likely to do well. However, why do some relapse?
It has been found that those without HER2-neu have a 5 per cent risk of relapse compared to 25 per cent for those whose cancers carry the gene. This knowledge has allowed us to select these 'poor players" for treatment to reduce their risk of relapse and death.
Similar findings are being made in many other cancers. In patients with colon and rectal cancers, all that mattered in the past was the stage of the disease. While this is still the most important determinant of long-term outlook, we are beginning to understand the relevance of yet another gene called epidermal growth factor receptor (EGFR). This gene has been found in many other cancers originating from the oral cavity, throat, lung, oesophagus and stomach.
Identifying the importance of molecular markers in cancers is only the first step in making a difference in the care of cancer patients. An equally important consideration is the ability to do these tests in clinical laboratories, not just specialised research facilities.
Clinical laboratories have, so far, kept pace with these advances in making these tests available to clinicians or doctors who see patients.
We have seen the cost of studying a pathology specimen go up from a few hundred dollars to a couple of thousand dollars. However, I am happy we have this option - because good medicine demands we know as much as possible about the cancer. The information allows us to customise therapies so that patients do not have to suffer from treatments that will not benefit them. This blundering about in the dark was what many doctors had to do in the past.
I am excited that all this is happening but I wish things could move faster. There are still many cancer genes out there waiting to be discovered. First, we need to find the genes and understand what they do. Second, we need to find the appropriate drugs to enhance or block these genes. Third, we will need to conduct clinical trials to prove the effectiveness of these drugs. The bench-to-bedside research, also called translational research, is what is needed to find new cures for cancer patients.
Singapore already has two medical schools (and is planning to have a third) producing about 300 doctors each year. This does not include many overseas medical graduates who come to work here. In medical care, what we need are not more clinicians like me, but more doctors and scientists who are willing to dedicate their lives to research. These researchers are the heroes of the medical fraternity, working in laboratories, searching for that elusive clue that may help save thousands of patients' lives.
Maybe one day, when I am done with patient care and if my hands are still steady enough, I will go back to school and learn how to slice a gene.
Dr Ang, the medical director of Parkway Cancer Centre, has been treating cancer patients for 23 years. In 1996, he was awarded Singapore's National Science Award for his outstanding contributions to medical research