Biomarker indicates patient susceptibility to treatment

According to a latest study, which revealed the presence of a unique genetic biomarker, the quality of life for patients undergoing treatment for colorectal cancer may be significantly improved, potentially minimising the unwanted side effects.

The work, carried out by the Mayo clinic, revealed the possibility of applying this knowledge to patient care. For example, identifying which patients are most vulnerable to these side effects before treatment would allow physicians to prescribe alternative treatments or take measures to counteract the nerve damage.

Using genetic information from the patient to tailor treatment is referred to as pharmacogenomic medicine, and is among the newest developments in cancer research. Pharmacogenomic information is believed to be the key to making the most effective and easily tolerated treatment choices.

The side effects associated with oxaliplatin (Eloxatin), a key component of modern chemotherapy for colorectal cancer, can include progressive nerve dysfunction with tingling, numbness, sensitivity to cold and over time, loss of manual dexterity needed for basic tasks of daily living such as buttoning shirts or tying shoelaces.

Mayo Clinic researchers describe how finding variations in genes of certain patients can help predict which group of patients are at higher risk to develop side effects from oxaliplatin early in the course of their treatment.

Because the variations occur in genes involved in detoxifying oxaliplatin, the researchers hypothesised that the variations could be used as biological markers that would indicate which patients are most susceptible to oxaliplatin's negative side effects. Results of the study confirmed this.

"Our research indicates that there is a group of patients who appear to have, based on genetic differences in an enzyme, a lower threshold to the toxic side effects of oxaliplatin," said Axel Grothey, the Mayo Clinic medical oncologist who led the study.

"If our finding is confirmed in a second trial, this could be of great clinical importance because it would enable those patients with a genetic makeup that predicts early onset of nerve dysfunction to either seek alternative treatment options right away, or to receive agents that protect the nerves," he added.

Dr Grothey emphasised that the findings were preliminary and needed further confirmation before they became widely available to patients.

If the findings are confirmed, additional research will be needed to develop neuroprotective agents that can shield the nerves from the toxic effects of oxaliplatin and alternatives to oxaliplatin-based chemotherapy.

In the United States, colorectal cancer is the fourth most common cancer in both men and women. In men, skin, prostate and lung cancers are more prevalent.

In women, skin, lung and breast cancer are more prevalent. While the exact cause is not known, risk factors associated with colorectal cancer include high-fat diets that are low in fruits and vegetables. The most common treatments are surgical removal of the diseased portion of the colon, chemotherapy and radiation treatments to halt cancer growth.

Many analysts predict that pharmacogenomics will revolutionise the way drugs are developed, tested, marketed and prescribed during the next decade, with the blockbuster business model of big pharmaceutical companies eventually giving way to a more targeted approach.

According to PricewaterhouseCoopers, the established business model pursued by the $250 billion (€189 billion) US pharmaceutical industry carries high risks and high costs, and the industry is under pressure from payers, providers, regulators and consumers to contain costs and ensure safety.

Blockbuster drugs, those with peak annual global sales of $1 billion and prescribed for general population use, can cost upwards of $800 million to develop, according to some industry experts, and take between 8 and 12 years to advance from the lab to the pharmacy. Yet these drugs are typically effective in only 40 to 60 per cent of the patient population.