A 'molecular' look at prostate cancer boosts treatment options
Treatment guidance for prostate cancer patients is not optimal because current clinical tests do not clearly differentiate between slow-growing and aggressive forms. An EU-funded project is addressing this by studying the underlying molecular mechanisms of the disease to enable personalised and effective treatment.
© Vitalii Vodolazskyi #159285112, source:stock.adobe.com 2020
There are around 1.3 million new cases of prostate cancer every year, making it the second most common cancer among men worldwide.
Not all prostate cancer patients require immediate therapy because in almost 45 % of cases the cancer is slow growing. These patients are frequently overtreated, creating adverse health consequences, because current clinical tests cannot accurately differentiate between slow-growing and aggressive forms of the disease.
On the other hand, immediate treatment with hormone (androgen deprivation) therapy is recommended for aggressive prostate cancer. However, if this fails, treatment options are limited, and advanced stages are regarded as incurable.
The EU-funded PCAPROTREAT project is addressing the clinical challenges of treating prostate cancer by improving the understanding of the diseases underlying molecular mechanisms. The aim is to use this new knowledge to develop novel and more effective treatments for prostate cancer.
After modelling the disease at the molecular level, we will identify molecules that can be targeted with drugs, says project coordinator Harald Mischak, CEO of Mosaiques Diagnostics in Germany. This approach is directed towards personalised medicine in prostate cancer, which attempts to guide the treatment of the disease based on each persons molecular profile.
To date, the project team has developed a comprehensive database on prostate cancer at the molecular level, conducted a protein-based analysis (proteomics) of patients with prostate cancer, and identified many new compounds as potential drug treatments.
The projects prostate cancer molecular knowledge base now includes data from 122 published studies which has been acquired by, among other means, using proteomics and other -omics technologies, such as gene expression analysis (transcriptomics). In parallel, PCAPROTREAT is using an experimental proteomics approach to analyse clinical samples. Urinary proteomics profiles acquired from over 800 patients with prostate cancer were used to identify proteomics patterns that are different between advanced and slow-progressing prostate cancer, explains Agnieszka Latosinska, the projects Marie Skłodowska Curie Actions Research Fellow.
Proteomics analysis was also performed on tissue samples taken from patients with prostate cancer. High-resolution mass spectrometry was used to characterise the full list of proteins present in each patient. Statistical analysis of these individual proteomes enabled the identification of unique proteins that are commonly altered in prostate cancer patients.
All these molecular features were consolidated, based on their function, and mapped on to molecular pathways. This analysis resulted in 56 new compounds that can be developed as drugs for prostate cancer, says Latosinska. To our knowledge, this is the first attempt aimed at the multidimensional multilayer/multi-omics molecular characterisation of prostate cancer to improve on available treatment options.
Effective novel treatments
The new drug candidates identified during the project will be taken forward into preclinical assessments. If successful, this will serve as a proof-of-concept that could have a major impact on drug development in general by showing how new drugs can be developed based on a multi-parametric molecular rationale.
Such an approach, when proven to be valid, will revolutionise healthcare as more efficient drugs are expected to be developed based on molecular pathology, says Mischak. It is expected that these drugs will be more specific and probably associated with fewer side effects and a lower probability of acquiring resistance.
The social impact of the results is expected to be very high as patients with slow-progressing prostate cancer are frequently overtreated. Therefore, the new approach could improve the quality of life of patients with slow-developing forms of prostate cancer, while providing novel treatments for the advanced disease, where efficient therapeutic options do not currently exist.
Therefore, better characterisation of the disease at the molecular level is expected to improve on the management of both slow-progressing and advanced prostate cancer, concludes Latosinska.
PCAPROTREAT is funded through the Individual Fellowships programme of the Marie Skłodowska Curie Actions (MSCA).