Synopsis
The role of molecular pathology in researching prostate cancer is complex. Multiple genes are involved in the pathogenesis of cancer disease, together with additional environmental factors. In the development of prostate cancer, researchers have demonstrated an intricate interaction of multiple genes and external influences. Recent research confirms that a significant number of men die with the disease, and not from it. The survival rate has improved, alongside developments in investigative tools like DNA microarray technology and the application of proteomics. These advancements have significantly enhanced the role of molecular pathology in prostate cancer research. Today we will explore and present the latest developments in prostate cancer on a genetic level.
Prostate Cancer Pathogenesis
Prostate cancer is the second leading cause of death in men. It is not invariably lethal but goes from asymptomatic to rapidly fatal systemic malignancy. Molecular pathology in prostate cancer has a compound role. Multiple genes are involved in cancer pathogenesis, but additional environmental factors like diet and inflammation are also involved. Research into prostate cancer has demonstrated a complex interaction of multiple genes and environmental factors, which can be important in individual cancer cases.
Prostate Cancer Prevalence
The prevalence of prostate cancer is so high that it could be considered a common age-related phenomenon. According to a study examining white Mediterranean males, 33% of men in their 8th decade had evidence of prostate cancer with necropsy and died with the disease and not from it. Data from postmortem studies show an even higher prostate cancer prevalence rate.
The Evolution of Research Technologies
The cases of morphologically identical prostate cancers often behave differently. Rapid advancements in understanding the genetic factors behind the initiation, development, and progression of prostate cancer are being made. This knowledge enables the distinction between indolent and aggressive tumors through molecular fingerprinting. Clinically, this could help avoid radical treatments and their associated morbidity in cases where prostate cancers have poor prognostic indicators.
The Role of Genetics
Inherited susceptibility genes suggest whether prostate cancer was caused by the interaction of multiple genes or not. Many studies focused on one gene at a time. However, it is a challenge to identify inherited susceptibility genes. Thus, future studies may need to consider the simultaneous effects of multiple genes.
Combined Effects of Multiple Genes
Analyzing multiple genes will involve larger sample sizes, especially if the effect of each gene is small. Microarray technology can examine multiple genes simultaneously. Talking about molecular pathology, sophisticated statistical models using DNA and cDNA microarrays allow the analysis of large numbers of genes and gene expression at a high resolution.
Major Challenges
The major challenge is the identification of features that can accurately predict the behavior of prostate cancer. The typical procedure, Gleason grading is a powerful prognostic indicator based on morphological features. However, there can be difficulties with interobserver reproducibility. Prostate carcinomas that are morphologically indistinguishable and discovered incidentally can behave in a clinically indolent way or aggressively.
DNA Repair
Over the last few years, major research emphasized DNA repair deficiency leading to the development of novel therapeutic approaches like poly ADP ribose polymerase (PARP) inhibitors. These inhibitors show therapeutic effects in tumors with a deficiency in the homologous recombination DNA repair pathway. This can be caused by either genetic or epigenetic mechanisms.
The Role of MMR Proteins
Another mechanism of DNA repair frequently altered in tumors is the mismatch repair pathway. Loss of function of one of the four nuclear enzymes, MMR proteins MLH1, MSH2, MSH6, and PMS2 results in a defective MMR pathway and microsatellite instability. Defective MMR causes a hypermutated tumor phenotype resulting in genomic instability and increased neoantigen burden.
Conclusion
Molecular pathology has a complex role in the diagnostics and research of prostate cancer. It is essential to highlight that multiple genes and external factors contribute to its development. These factors are in complex interaction with each other. Prostate cancer still represents a great problem on a global level when talking about mortality rate as the mortality rate is still high worldwide. DNA microarray technology is one of the most significant developments in the field of molecular pathology and contributes a lot to prostate cancer diagnostics and research. Despite that, the identification of features that can accurately predict the behavior of cancer still represents a major challenge for clinicians. DNA repair and mismatches are at the moment the most effective solution.
