Development of Biomarkers and Biotherapeutics is Heavily Reliant on Analytical Science

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The 1980s saw the introduction of the first biotherapeutic – recombinant human insulin for the treatment of diabetes mellitus (DM). This drug replaced bovine and porcine as sources for this hormone as it had a higher purity, specificity, and efficacy. It was also a more cost-effective source of treatment.

Since then, biotherapeutics have demonstrated high specificity and effectiveness compared to their small, chemical counterparts of the pharmaceutical industry, resulting in a dramatic increase in total annual revenue from $4.4 billion in 1990 to more than $275 billion today.

The National Institute of Health defines biomarkers as “characteristics that can be objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention.” The majority of biomarkers that have been identified to date are small biological molecules and, based on the concentration of these substances, clinical decisions can be made in the diagnosis and treatment of the specified diseases. These molecules are often used as targets based on the development of new biotherapeutics.

Characterization is Key

Biotherapeutics tend to be large, complex molecules, often with posttranslational modifications (PTM) due to their production in biological sources, such as yeast and bacteria.

Using high throughput ‘omic’ technologies, potential biomarkers are identified from complex biological samples, such as tissues, cell lines, and biofluids, which contain thousands of substances. Therefore, in both fields, analytical chemistry is an essential tool as it provides sample separation and in-depth structural characterization.

Depending on the analytical tool, information on a sample's structure at the atomic scale can be uncovered to its three-dimensional ordering. Each technique comes with its inherent advantages and limitations. Therefore, analytical instrumentation is often combined to provide a platform that gives comprehensive qualitative and quantitative information.

For the discovery of biomarkers, gas chromatography (GC) or liquid chromatography (LC) is commonly coupled with nuclear magnetic resonance (NMR) or mass spectrometry (MS). The chromatographic section provides a thorough separation of the molecules in the complex biological mixtures, while NMR or MS deduce the structural composition of the substances in the sample.

Discovery of Novel Biomarkers for Diabetes and Cancer

The incidence of type 1 and type 2 DM has now reached epidemic proportions, with 700 million people expected to be living with the disease by 2045. Despite an increase in understanding the disease's pathogenesis, glucose remains the only biomarker to aid diagnosis. Recent work has demonstrated that two-dimensional GC and time-of-flight mass spectrometry (GCxGC-TOFMS) enables analysis of complex type 2 DM samples. Several biomarker candidates were identified by analyzing a mass range of 40 to 650 Da with statistical data processing.

Cancer is also a significant public health problem, with an expected increase to more than 20 million new cancer cases each year by 2025. The only definitive way of diagnosing cancer is through a tumor tissue biopsy. However, gathering cells from a tumor to perform the biopsy can be very difficult, and the results only provide information about the disease at that point.

The discovery of three tumor-derived biomarkers, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and extracellular vesicles (EVs), has initiated the development of liquid biopsies. This technique uses samples of bodily fluids, taken by a non-invasive procedure, to analyze these biomarkers and aid in cancer diagnosis. A liquid biopsy process using saliva has been shown to detect ctDNA with >95% concordance to tumor tissue biopsy and delivers results in 15 minutes.

Pittcon: The World Leading Conference in Analytical Science

These developments, along with many others in the biotherapeutic and biomarker fields, will be presented at Pittcon, the world’s leading conference and exposition on analytical chemistry and scientific instrumentation.

Due to the coronavirus pandemic, scientific dissemination, and collaboration are more vital than ever. This year’s virtual Pittcon conference takes place on 8-12 March and promises to be a truly global event due to its accessibility.

With over 2,000 sessions in the technical program, new developments in all areas of life science will be presented. All major analytical manufacturers, including Bruker, Shimadzu, Agilent, Thermofisher, and Advion, will be present at the exposition with online stalls for instrument demonstrations and discussions with technical experts.

This meeting of top-class scientists and analytical companies will provide a platform for further development in biotherapeutics and biomarkers discovery. It will also help move these fields towards achieving future objectives of using biomarkers to screen high-risk populations for individual diseases and prescribe the most suitable biotherapeutic and dose for personalized medicine.  

References

1. Landgraf, W., et al. (2016). Recombinant Human Insulins – Clinical Efficacy and Safety in Diabetes Therapy. European Journal of Endocrinology. doi: 10.17925/EE.2016.12.01.12.
2. Rader, R. A. (2018) Biopharma Market: An Inside Look. https://www.pharmamanufacturing.com/articles/2018/biopharma-market-an-inside-look/
3. Naylor, S. (2003). Biomarkers: Current Perspective and Future Prospects. Expert Review of Molecular Diagnostics. doi: 10.1586/14737159.3.5.525.
4. Hare, D. J., et al. (2016). On the Outside Looking In: Redefining the Role of Analytical Chemistry in the Biosciences. Chemical Communications. doi: 10.1039/c6cc00128a.
5. Laakso, M. (2019). Biomarkers for Type 2 Diabetes. Molecular Metabolism. https://doi.org/10.1016/j.molmet.2019.06.016.
6. www.pittcon.org. (2021). High Performance GC- and GCxGC-TOFMS Metabolomics-Based Approach for Discovery of Potential Diabetes II Biomarkers in Human Serum. https://s23.a2zinc.net/clients/Pittcon/PIT21/Public/SessionDetails.aspx?FromPage=Sessions.aspx&SessionID=4773&SessionDateID=16.
7. Zugazagoitia, J., et al. (2016). Current Challenges in Cancer Treatment. Clinical Therapeutics. http://dx.doi.org/10.1016/j.clinthera.2016.03.026.
8. www.pittcon.org. (2021). Saliva EFIRM Liquid Biopsy. https://s23.a2zinc.net/clients/Pittcon/PIT21/Public/SessionDetails.aspx?FromPage=Sessions.aspx&SessionID=2714&SessionDateID=18.
9. www.pittcon.org. (2021). Science: Now More Than Ever. https://pittcon.org/pittcon-2021/