Cancer is a group of about 200 diseases that share the characteristic that cell growth rates exceed their rates of death. It is now clear that this is due to mutations or alterations to the normal systems that regulate cell division. Everybody is dealt a different hand of genetic changes, but some individuals are dealt a hand that results in more aggressive or less drug-responsive disease. Unfortunately, it is very unlikely that a particular cancer is a result of just one genetic change. In solid tumours, cancer is probably the result of something like five genetic changes. In contrast, ‘liquid’ tumours such as leukaemia may require fewer genetic changes. Different tumours will be the result of different genetic changes and, consequently, it is highly unlikely that a single drug will cure every patient with cancer.

Multiple Genes
Multiple genes have been identified that are linked with cancer and the majority of these genes regulate cell growth. For example, over-expression of epidermal growth factor receptor (EGFR) is common in many solid tumours, such as colorectal and lung carcinomas, as well as cancers of the head and neck. EGFR over-expression correlates with increased metastasis, decreased survival and a poor prognosis. EGFR is also reported to protect malignant tumour cells from the cytotoxic effects of chemotherapy and radiotherapy, making these treatments less effective. The protein product of the EGFR gene is tyrosine kinase, an enzyme that provides a central switch mechanism in cellular signal transduction pathways.As such, it is involved in many cellular processes, such as cell proliferation, metabolism, survival and apoptosis. Several tyrosine kinases are known to be activated in cancer cells and to drive tumour growth and progression. Inhibition of EGFR-associated tyrosine kinase represents a tried and tested approach to the treatment of solid tumours. Therapeutic strategies include blocking kinase-substrate interaction, inhibiting the enzyme’s adenosine 5-triphosphate (ATP) binding site and blocking extracellular tyrosine kinase receptors on tumour cells. Several tyrosine kinase inhibitors (TKIs) have already been approved as anti-cancer agents.

Biomarkers
Biomarkers have been around for many years, but in cancer drug development they have only become significant relatively recently.There are several classes of these new oncology-focused biomarkers. First are those that permit the detection and possibly the diagnosis of cancer (such as the well established test for prostate-specific antigen (PSA) in prostate cancer patients), and these are often used to give an indication of response to therapy and early relapse, as they are essentially markers of tumour burden.