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Today is World Cancer Day. In light of this, we asked Elaine Holmes, Member of our Pharmacology & Drug Discovery Faculty, to give us an overview of biomarkers of cancer.

Globally, cancer is among the leading causes of death with the number of new cases projected to rise to 22 million over the next two decades.  Breast, lung, prostate, colorectal cancers are amongst the most common cancers but rising incidences of pancreatic, liver, thyroid and melanoma reflect the impact of changing environmental risk factors. There is a critical need for new and reliable biomarkers to allow early detection of disease or provide a measurement of how well a patient is responding to therapy.

What are biomarkers?

A biomarker is a biological characteristic that is objectively measured and evaluated as an indicator of normal biological or pathological processes, or a response to a therapeutic intervention. Examples include patterns of gene expression, levels of a particular protein in body fluids, or changes in electrical activity in the brain.

Biomarkers and cancer

In cancer, biomarkers can be chemicals secreted by tumours themselves or chemicals that reflect the body’s response to cancer. Current biomarkers of cancer tend to lack sensitivity or specificity. For example, the prostate-specific antigen (PSA) blood test, is used to screen for prostate cancer but levels of PSA can also be elevated in response to benign prostate conditions. This means that the number of false positives are high and that PSA is not an effective tool for reducing the number of prostate cancer deaths.

More recently, increasing emphasis has been placed on biomarkers that are prognostically predictive of an individual’s response to a drug, thereby enabling stratification of the patient population with respect to clinical course of action. To be effective, the biomarker should be indicative of the presence of a specific cancer, be highly reproducible, easy to detect and preferably inexpensive.

Biomarkers of cancer risk are also an important part of the picture and advances in genomic, epigenetic, proteomic, glycomic and metabonomic technologies has resulted in the identification of new biomarkers in the cancer arena such as REP522, a repetitive non coding RNA sequence identified by the FANTOM5 consortium using Cap-Analysis Gene Expression (CAGE) technology. The battery of ‘omics technologies provides a framework for understanding the molecular changes underpinning the conversion of normal cells to cancerous cells and provides a framework for localizing the tumour and assessing stage and severity of the pathology. The field of epigenetics holds promise to deliver new understanding of aetiology and risk.

Biomarkers in Imaging

Imaging of tumour biomarkers has moved beyond positive emission tomography (PET) and new mass spectrometry methods such as Desorptive ElectroSpray Ionisation (DESI) imaging are being used to identify the location of chemicals on the surface of the tumor with respect to its composition as well as its surrounding tissue environment. DESI provides good spatial resolution, sensitivity and information recovery from frozen section material in order to achieve histopathological classification and provides more refined guidelines for tumour based on metabolic changes in the tumour environment, which gives a new dimensionality to tissue analysis.

Early response to therapeutics

Biomarkers of early response to therapeutics or indicative of drug resistance are the holy grail of clinical management strategies. Development of traditional cancer drugs that rely predominantly on cytotoxicity has driven dosage to a point of maximum tolerance, often associated with high levels of toxicity. Biomarkers of pathway responses allow for a more subtle tailoring of drug targets to block synthesis of specific molecules or pathways rather than global cytotoxic chemotherapies. Targeted molecular antibody-drug conjugates with the ability to deliver cytotoxic drugs to localised tumour cells or tissues will potentially revolutionise the therapy landscape by optimizing tumour exposure and minimizing peripheral toxicity.

Biomarkers and Big Data

As the era of ‘Big Data’ comes into play, the role of bioinformatics and data mining are coming into their own for compiling comprehensive lists of cancer biomarkers. Researchers from Sheffield, Coventry and Warwick combined bioinformatics forces to collate and functionally group 788 biomarkers from over 19,000 studies performed over the last five years. The ability to collate, co-analyse and visualise clinical and analytical data from large cohorts of individuals using advanced bioinformatics infrastructure and algorithms will open new doors to researchers and provide a forum for sharing data to advance knowledge.

The need for cancer biomarker research is emphasized by dedicated funding initiatives from Cancer Research UK (CRUK) and other funding bodies, which focus not only on discovery but validation of the biomarker in a clinical setting. The CRUK outlines three phases of biomarker development, namely demonstration of accuracy and reproducibility, assay optimisation and SOP development and finally development of the assay to GCLP standards.