open access: British Journal of Cancer - Cancer heterogeneity: implications for targeted therapeutics

British Journal of Cancer - Cancer heterogeneity: implications for targeted therapeutics

Clinico-pathological heterogeneity and its molecular basis

"Morphological variation between different regions of a tumour has long been familiar to histopathologists. For this reason, it is routine for pathologists to examine multiple sections from the same tumour, but to report only the highest grade. Nuclear pleomorphism is another example of intra-tumour heterogeneity, which is accounted for in breast cancer grading. It is also readily apparent to those clinicians treating cancer that there is marked variation in tumour behaviour between patients with the same tumour type, and between different tumour sites in the same patient; the latter is usually manifested as differential or mixed responses to therapy (Figure 1).

Intuitively, common clinico-pathological observations such as these could be attributable to intra-tumour heterogeneity, but studies are only now beginning to formally evaluate this relationship. It is also likely that other factors, such as pharmacodynamics, contribute to the non-uniformity of drug response.....