Editorial [Hot Topic: Cancer Biomarkers Guest Editor: Robert C. Rees]

Cancer is a genetic disorder resulting in a change in cell growth pattern, cell phenotype and functional traits. Tissue integrity is challenged as a result of malignancy, placing the host-cell equilibrium under threat. In particular the immune system may respond to cancer in several ways: (1) to the benefit of the host by mediating the destruction of the malignant cells, (2) provide the tumour with an additional growth advantage by changing the tissue micro-environment to enhance tumour cell survival and growth potential or (3) become tolerant to the presence of the tumour through interaction with tumour or host cell derived products, thereby allowing the tumour to develop “unchecked”. Although single biomarkers have been identified for several cancers, the dynamic biological relationship between the host and the cancer will be reflected through extensive and differing genetic, protein and cell response “signatures”, derived from both host and tumour cells. Biomarkers may predict the presence of cancer and associate with diagnosis, prognosis and outcome of therapy. The development of advanced bio-molecular techniques for the interrogation of complex genetic, protein, biological data and clinical parameters has led to new opportunities for defining cancer biomarkers. There is a pressing need for more reliable markers that associate with disease status and importantly with response to therapy. Many cancers are detected late in the disease process when more aggressive therapy is required and although treatment may succeed in eradicating the disease it is often difficult to predict patient outcome following treatment. It is well reported that first line treatment may fail to stem the disease course; thus, providing a more accurate assessment of the likely outcome of therapy would allow appropriate treatment options to be administered at an earlier stage. For these reasons it is important to focus research on the identification of new cancer biomarkers with predictive capability. This publication provides an insight into important research areas of current interest, describing “state of the art” methods that are being used to identify new, disease -associated genes / gene products that have utility as cancer biomarkers. Many of the studies focus on markers detected in response to immunotherapy, for example, where a specific immune response can be defined and monitored, which in some cases may be indicative of patient outcome. This involves the assessment of adaptive Tcell mediated immunity and innate immune mechanisms using phenotypic and functional characteristics or the measurement of soluble serum factors produced either by leukocyte populations or as a consequence of host cell - tumour cell interaction (Pawelec et al., Dodi et al., Schadendorf et al.). Some of the many characteristics of cancer cells, for example the loss of MHC which represents a tumour escape mechanism, have been recognised as indicators of patient prognosis (Garrido et al.). Another important area of research focuses on profiling autoantibody responses against tumour -associated proteins, many of which have been discovered through screening cDNA libraries and antigen arrays. Protein micro-arrays in particular may prove to be beneficial for the rapid screening of patient sera for antibody responses to onco-proteins and normal cellular proteins (Miles et al.). Gene arrays and interrogation for the serum and cancer cell proteome using currently available separation and analytical methods coupled with bioinformatic analysis of complex data sets, allows an integrated approach to be adopted for biomarker discovery. The combined assessment of proteomic, genetic, immunological and clinical data may prove to be of greater value in defining a set of markers with greater accuracy of prediction (Laversin et al.). This issue further continues with reviews on cancer diagnosis, prognosis and predictive responses that are likely to influence therapeutic intervention in the future. The host-cancer relationship is complex and the sequel of pathological mechanisms occurring during progression of the disease will dictate the genetic and protein expression profile that can be detected. Biomarkers may be used to predict the presence of cancer, although there is a continuing need for more reliable indicators of disease and it is unlikely that single biomarkers will prove to be accurate and reliable. The paper by Labarriere et al. describes the current status of research using adoptive cellular therapy, as developed by the group of Francine Jotereau in Nantes. They describe the clinical and biological consequences of adoptive T-cell transfer and the clonal response and T-cell phenotype / genotype associating with long term patient survival. Mihaylova et al. further discusses the role of NK associated ligands and receptors as potential markers associating with susceptibility to cancer. The paper includes important concepts of KIR - HLA interactions and NKG2D -Mic proteins, that impact on genetic diversity.