Chemotherapy is used to treat many types of cancer and indeed is the only method of treatment for patients with leukaemia. There are over 30 drugs to choose from that are regularly used in the clinic and many more in different stages of drug development. Whilst it is known that certain drugs are more effective in certain types of cancer, a patientís individual response to chemotherapy is not normally assessed before treatment. Researchers have been trying to customise therapy to individuals ever since the advent of chemotherapy but it was only in the last couple of decades, with advances in technology, that this became feasible. As a result, chemosensitivity testing has now been validated for both leukaemia and solid tumours and, as a consequence, it is now possible to avoid using ineffective drugs so sparing patients the side effects normally associated with these agents. Chemosensitivity testing also allows the selection of drugs which appear sensitive in the laboratory so offering patients a better chance of response.
Drug resistance can occur at the onset of the disease or can be acquired after previous chemotherapy. In order to identify drug resistance before treatment using chemosensitivity testing, a sample of the patientís tumour, whether it be bone marrow for leukaemia, a biopsy taken at operation or a cellular fluid drained from the tumour site, is collected into special culture medium and sent to the laboratory. The cancer cells are then separated, checked and prepared for mixing with the proposed chemotherapy drugs. These drugs are diluted down to the same concentration as would be found in the body during treatment. The cells are then incubated in similar conditions as are found in the body for 2-4 days. At the end of this drug exposure, it is just a case of measuring any tumour cells that remain alive. There are several methods that can be used for this from a simple dye colour change to a sophisticated luminescent technique. Rather like testing bacteria for the best antibiotic, it is a very simple yet effective procedure.
Despite the fact that chemosensitivity testing is used widely with the US and Europe, there are only 3 laboratories offering this service in the UK today - in Pembury, Kent, in Portsmouth and in Bath. Indeed funding for this approach is hard to find in the UK. The use of this technique has obvious benefits for the patient by pointing the way to the best drugs for them but, furthermore, there are health economic benefits that could add up to millions of pounds being saved on drugs bills alone. By selecting the most effective drugs at the outset of the disease, lengthy hospital stays and support therapy could be minimised. It is, of course the benefit to patients that interests us the most and we have found that chemosensitivity testing invariably shows a predictive accuracy of over 90% to identify drugs that will not work i.e. drug resistance. By avoiding these agents and using drugs found sensitive in the laboratory we have found that patients with advanced ovarian cancer; for example, live twice as long as their counterparts treated with conventional agents which, nevertheless, were found to be resistant. The time is ripe to include chemosensitivity testing as a routine adjunct to help improve existing chemotherapy. It could save millions of pounds for the NHS by eliminating ineffective agents. These tests cost a tiny fraction of the existing drug bill so the cost effectiveness cannot be disputed.
In our laboratory in Pembury we have extended our studies by attempting to determine why some patients will respond to certain chemotherapy whilst others, with exactly the same disease, do not. It is possible to determine how cancer cells are protecting themselves from these drugs. This enables the selection by chemosensitivity testing of other drugs which do not necessarily kill cancer cells on their own but, in combination with conventional chemotherapy can overcome drug resistance and re-sensitise the cells, so offering a further chance to patients.
Another area to which chemosensitivity testing lends itself is as an extension to the existing development of new drugs. New drugs with novel mechanisms of action are still required for the battle against cancer. Currently, drugs under development are initially selected by their effect on experimental tumour models. Firstly they are screened against cells growing in perpetuity in the laboratory. These cells may have come originally from a patient with cancer anything up to 30 years ago and therefore have had many chances to mutate and most probably bear no resemblance to the primary tumour from which they were originally sampled. Possible candidates are further selected by more experimental modelling. If the agent appears effective in this system then the drug goes straight to the clinic to be tested in drug trials in patients. We firmly believe such novel agents should be tested in the laboratory against tumour cells taken directly from patients to compliment the other tests and confirm their effectiveness before they are given to patients.
So, in conclusion, chemosensitivity testing has many benefits. Most importantly for patients but also in monetary terms for the NHS and for pharmaceutical companies to help their search for better more effective agents to treat this devastating group of diseases.
Jean Sargent Ph.D.