A new safer drug toxicity test to minimize the drug failure rates in clinical trials for cancer treatmants has been developed.
The preclinical test platform would enable researchers to study drug toxicity on a molecular level other than using tissue slices from the cancer patient.
Researchers can analyse numerous tumours from different patients,identify differences in drug response between those patients, and to understand variations of response in cell subtypes within one tumour based on freshly cultivated intact tissue from surgically treated cancer patients.
Currently, most tests for drug metabolism and toxicity testing are using tissue slices of normal organs like liver, kidney and lung to detect efficacy of cancer drugs.
The new toxicity test also helps to identify biomarkers that can predict drug response for patients entering a clinical trial, allowing researchers to include only those patients whose participation will provide a significant answer to the question being asked.
The new toxicity test was created specifically for oncology drug testing and uses tumour tissues from colorectal and lung cancer patients.
A major problem of drug development at present is the inability to extrapolate response in preclinical cell models to patients.
“Approximately 90% of clinical trials fail because the drugs used are too ineffective or too toxic,” explained Dr Ilona Schonn, Director of Cell Culture Research at Indivumed GmbH, the lead researcher from a team of scientists from Hamburg who have developed the new test.
Frequent drug failures in clinical studies result in unacceptably high costs for drug development. It also exposes patients to risks from toxicity or simply wastes their time in testing a substance which proves to be ineffective.
Drug failures arises from the fact that patients respond individually to drugs. In addition, each tumour consists of a variety of different cancer cells that interact in different ways with the framework of individual non-tumour cells, resulting in highly variable growth behaviour and response to drugs.
The new pre-clinical test would eliminate drug failure problems in clinical trials and provide an accurate model of individual patient response.
The new test allows scientists to translate findings from commonly used cell lines to a preclinical model which is as close as possible to using the same drug in the clinical setting. This enables a better estimate of the number of patients who are likely to respond to the treatment.
The test can be of great benefit for pharmaceutical companies because it allows the analysis of samples from meaningful number of patients with different tumours in a short period of time. This could accelerate progression of a potential new treatment to clinical trials.
Together with all the clinical patient data and several analytical test systems such as signalling pathway analysis, the researcher have been able to characterise individual tumours in more detail. This will improve the understanding of drug effects and treatments, a step forward towards the goal of individualised cancer therapy, according to Dr Schonn.
The new test can also help gain more knowledge about the mode of action of a new compound in patients, and identify optimal disease areas, for example tumours with particular mutations or over-expression of target receptors, and dosage.
Normally toxicity tests have only been validated in colon, non small cell lung, and breast cancer tumours. But this type of toxicity testing leaves no reason to think that it would not be equally accurate in other solid tumour types, the scientists say.
Since the test allows researchers to maintain the complex environment of the primary cancer tumour,it holds out great promise for the quick and effective elucidation of response to anticancer drugs, researchers believe.
The new toxicity test would be able apply it to a growing number of drugs emerging from the labs of pharmaceutical companies to help to shorten development time and to make clinical trials both more efficient and safer for patients, hopes Dr Schonn.