Oncologist's/haematologist's view on the roles of pathologists for molecular targeted cancer therapy

Abstract

In the past two decades there has been a tremendous increase in the understanding of the molecular basis of human malignancies. In a variety of neoplasms, specific molecular markers became part of disease classifications and are now routinely used to define specific entities. Molecular analyses discriminate prognostic groups, guide differential treatment strategies and identify targets for molecular defined cancer therapy. A battery of new drugs has been developed to specifically inhibit oncogenic pathways. For an increasing number of solid and haematological malignancies, the availability of molecular targeted drugs has fundamentally changed treatment algorithms. However, the diagnostic, prognostic and therapeutic impact of selected molecular markers is still limited in many cases. After all, the success of a molecular targeted therapy is clearly determined by the significance of the targeted structure for the biology of cancer and the ability of the malignant cell to evade specific inhibition.

Fig 1

Treatment algorithm in Bcr-Abl⁺ CML. Abbreviations: qRT-PCR, quantitative real-time PCR; CHR, complete haematological response; PCyR, partial cytogentic response; CCyR, complete CyR; AP, accelerated phase; BC, blast phase; Allo-Tx, allogeneic stem cell transplantation.

Fig 2

EGFR targeting in solid tumours: current/ possible future implication of molecular assessment. (A) EGFR TKI in NSCLC. (B) EGFR antibody treatment in CRC. Abbreviations: EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor.

Fig 3

Biomarkers analysis in molecular targeted therapy trials. The pathologist’s role comprises drug target discovery and biomarker identification, as well as evaluation of toxicity and efficacy in normal and tumour tissue samples.