Using Biomarkers to Identify Inflammation in Prostate Cancer Patients
Article Mar 30, 2016
Prostate cancer is on the rise and, like other cancers, exhibits many complex phenotypes. Chronic inflammation is common in malignant and non-malignant prostate cases and is a frequent cause of false-positive diagnoses. In a recent industry-academia collaboration, biomarkers for chronic inflammation were identified in prostate cancer patients, leading to the potential to identify high inflammation in patients without the need for biopsies. These biomarkers could be used as new drug targets and as part of the route to companion diagnostics development and personalised medicine.
Prostate cancer is the second most common cancer in men worldwide and accounted for around 8% of all new cancer cases in 2012. One of the challenges in tackling prostate cancer is achieving an accurate diagnosis and prognosis. Patients are commonly screened and assessed for prostate cancer using blood tests measuring the levels of prostate-specific antigen (PSA) and a physical examination. If these tests are positive or there are other indications of an enlarged prostate or abnormal tissue growth, more detailed anatomical and molecular diagnostic analyses may be conducted.
A common feature of prostate cancer and disease is inflammation. Some evidence suggests inflammation of the prostate might increase the likelihood of the development of cancer. Conversely, inflammation is also thought to sometimes occur in response to prostate cancer, and whether this aids in combating the cancer or promotes its progression remains an active debate.
The need for improved diagnosis and patient stratification
The causes of both cancer and inflammation are extremely varied, since they are the result of complex genetic rearrangements in the human genome. The different disease subtypes caused by these rearrangements lead to the production of unique biomarkers. Not only do these biomarkers hold great potential for better, more accurate diagnoses, they can also serve as potential drug targets and enable the profiling and differentiation of specific patient subgroups, supporting the development of companion diagnostics and a more personalised medicine approach.
A common molecular diagnostic test currently used for prostate cancer is the PSA test, which assesses the presence of an antigen commonly found in prostate cancer. One of the limitations with this test is that prostatitis and other prostate problems can cause increases in PSA levels, leading to false positive results. Another problem is that the PSA test does not give any specific indication of the stage of the disease nor of the presence or absence of inflammation. If more reliable and informative tests could be used, a more accurate diagnosis could be achieved and treatment plans could be tailored for patient groups to increase the chances of success.
The identification of new biomarkers specific for inflammation in prostate cancer
A recent study aimed to identify and validate new molecular markers of inflammation in prostate cancer. The researchers used a protein array containing antigens known to be enriched in prostate cancer patients to screen for the new molecular markers. From patients exhibiting either low or high inflammation in the prostate, they identified autoantibodies associated specifically with high inflammation. Candidate biomarkers were confirmed using an independent assay by another industrial partner in the study, and several promising biomarkers were highlighted. These showed a sensitivity to high inflammation of 80% and a diagnostic specificity of 67%. The researchers would like to follow up this study with a larger patient cohort that includes both prostatitis and prostate cancer patients at different disease stages, so that biomarkers facilitating patient stratification might be identified.
This research was conducted by industrial and academic collaborators and is a good example of how such collaborations can efficiently fill the gap between fundamental and applied research, bringing the benefits of scientific research to peoples’ health and wellbeing.
Improved treatment and companion diagnostics
As the average age increases in developed countries, the incidence of prostate cancer and the associated medical problems follow suit. If inflammation in the prostate increases the probability of cancer development then early medical treatment of inflammation might help prevent or delay the disease. “The biomarkers we identified might facilitate early intervention in prostate cancer, and could have several other benefits”, said Dr Stefan Müllner, CEO of Protagen. “We hope that identifying inflammation will assist researchers in clarifying the impact of inflammation on prostate disease. Molecular diagnostics could abrogate invasive diagnosis and could identify novel drug targets for personalised medicine.”
Personalised medicine entails intelligent drug choices that are deemed optimal based on several molecular and physical indicators exhibited by the patient. As this new area of medicine becomes more accessible there is hope that it will improve patient outcomes and reduce costs for health services and the tax payer by enabling faster pre-clinical and clinical development, as well as the adoption of smaller, targeted and more cost-effective trials. This is especially important in cancer where every case varies at the molecular level and various treatments are attempted in order to find out which treatment is effective. Some treatments cause more harm than good and it would be extremely beneficial if we could avoid these by predicting their outcome.
The world of microfluidics has generated a host of intricate tools on a microscale, ranging from cheap paper-based lateral flow tests to organ-on-a-chip models designed to facilitate personalized diagnostic tests.
This article explores the extent to which microfluidic tools are filling a gap in clinical and point-of-care diagnostics, and touches on how microfluidics could improve the drug discovery process.
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