Relevance of the stroma in pancreatic ductal adenocarcinoma and its challenges for translational research
Ashenafi Bulle1, Jeroen Dekervel1, Schalk van der Merwe2, Eric Van Cutsem1, Chris Verslype1 and Jos van Pelt1*
Pancreatic ductal adenocarcinoma (PDAC) is the fourth most lethal tumor around the world and stands out from many other cancers. Despite increasing research for better diagnostic and treatment strategies, there has hardly been a substantial improvement over the last decades in the 5-year survival. This is mainly because, at the time of diagnosis, the cancer cells have already migrated and invaded distant organs and tissues. At this stage, patients in most cases are ineligible for surgery and their response to conventional therapies, such as radiotherapy and chemotherapy, is also very poor.
Researchers have mainly been targeting the genetic alterations of the cancer cells, and these genetic therapies in pancreatic cancer have significantly failed to improve patient survival. It is true that the early stages of tumor formation are based on a combination of genetic and epigenetic alterations that activate oncogenes and/or inhibit tumor suppressor genes, but progress in PDAC is mainly orchestrated by microenvironmental factors. Recently, targeting tumor microenvironment components that play a prominent role in tumor progression (fibrous tissue, angiogenesis, hypoxia, tumor-associated macrophages, etc.) have begun to attract the focus of cancer researchers. In addition, immunotherapy, which has shown some success in other types of cancer, is now also emerging for pancreatic cancer for which the microenvironment possess specific challenges.
This review highlights current obstacles and opportunities in pancreatic cancer research and treatment (in vitro and in vivo (patient-derived tumor xenografts and genetic engineered mouse models)) and also indicates future directions to be explored as a potential strategy to improve patient outcomes.
DOI: 10.29245/2578-2967/2018/1.1112 View / Download Pdf Commentary: "Aptamer-functionalized hybrid nanoparticle for the treatment of breast cancer"
Ronise Evans
The major theme throughout this paper was solving the problem of multidrug resistance (MDR) in chemotherapeutic remediation for breast cancer patients by an aptamer-labeled hybrid nanoparticle to enhance selective delivery of siRNA into tumor cells and produce an enhanced knock-down of P-glycoprotein (P-gp); which was detected mainly by western blot. The primary focus of this study was to know whether labeling nanoparticles with a cancer cell specific aptamer could enhance selective delivery of siRNA into tumor cells leading to enhanced knock-down of P-glycoprotein or P-gp as compared to non-labeled nanoparticles. The goal is to minimize cancerous gene expression by silencing its mRNA. Target specificity is not only key in completing this goal, but it is also necessary regarding, biodegradability, cytotoxicity and immune response. To accomplish this goal, the design methods had to be meticulous and carefully researched andapplied.
DOI: 10.29245/2578-2967/2018/1.1103 View / Download Pdf Prostate Cancer Detection: Complexities and Strategies
Julie-Ann O’Reilly1*, Richard J. O’Kennedy1,2
Prostate cancer (PCa) incidence is increasing due to the ageing worldwide population. In recent years, the unsuitability of prostate specific antigen (PSA) as a diagnostic biomarker has become apparent. Unnecessary treatment of men with non-lethal disease leading to significant quality-of-life reducing side-effects resulted in 2017 in the US Preventative Services Task Force (USPSTF) recommending selective and limited use of PSA testing for PCa. An immediate need exists for a test capable of accurate and early diagnosis of PCa. Critically, this test must differentiate between indolent and aggressive PCa to inform appropriate management of the disease. The key to predictive accuracy is the utilisation of combinations of diverse biomarkers and clinical data. A number of suitable new tests have emerged since 2013 but none of these have been implemented in the clinical setting. Extensive clinical validation of these tests is critical to address the chasm that now exists in PCa diagnostics. This mini review assesses current clinical issues for PCa diagnosis, evaluates currently available commercial tests and critically assesses next-generation diagnostic tools that could revolutionise PCa diagnostics.
DOI: 10.29245/2578-2967/2018/1.1111 View / Download Pdf