An article available as an uncorrected proof in the journal Drug Discovery Today has reviewed the role of nanomedicine in the pathology and genetics of pancreatic cancer.
Study: Nanomedicine for overcoming therapeutic and diagnostic challenges associated with pancreatic cancer. Image Credit: mi_viri/Shutterstock.com
The Impact of Pancreatic Cancer
Pancreatic cancer is one of the leading causes of cancer-related deaths in the USA, with a significant number of individuals succumbing to the disease every year. The low five-year survival rate makes pancreatic cancer more deadly compared to other cancers.
The development of this cancer starts from the damage to pancreatic deoxyribonucleic acid (DNA). Later, the mutated/damaged pancreatic cells transform into a tumor and grow abnormally by feeding on the nutrients available in the pancreas.
Distinct pancreatic cancer symptoms emerge only after the initial stages of disease progression, which delays diagnosis and limits treatment options. Moreover, the symptoms, such as weight loss, vomiting, and nausea, are often confused with symptoms of other less severe disorders.
The existing imaging technology cannot effectively detect small masses, such as tumors, in the pancreas. These factors are collectively responsible for the late detection of cancer when most of the treatment alternatives, such as surgical tumor removal and/or chemotherapy, become implausible.
However, significant advancements in the field of cancer research and nanomedicine in the last few decades have helped achieve a better understanding of the disease, which has allowed the development of more effective treatment and early diagnosis of the disease.
Pancreatic Cancer: Pathology
The poor diagnosis of pancreatic cancer can be attributed to several factors, such as lack of effective detection technology and treatment alternatives, the adverse impact of chemotherapeutic drugs, postoperative disease recurrence, and acquired immune privilege.
Although a biomarker with adequate specificity and sensitivity is required for effective screening of pancreatic cancer, no such biomarkers are currently available that satisfy these criteria.
In terms of treatment alternatives, surgical resections, although safer than other options, are ineffective in controlling pancreatic cancer.
Chemotherapy combined with chemoradiation or systemic chemotherapy can lead to a number of adverse effects that are detrimental to the rapidly dividing body cells, such as hair follicle cells. Thus, ideal pancreatic cancer treatment would require targeting intraductal papillary mucinous neoplasm (IPMNs) or pancreatic intraepithelial neoplasias (PanINs) at the early stages in order to prevent them from becoming malignant and increase the effectiveness of surgical resection.
Nanotechnology-Based Drug Delivery Mechanism
Recently, the use of nanoparticles (NPs) that mainly comprised of biodegradable materials, has gained prominence for effectively delivering a number of chemotherapeutic agents to the target tumor sites. NP-based drug delivery mechanism possesses multiple benefits that include enhanced drug penetration and reduced toxicity.
Additionally, NPs can substantially reduce the possibility of tumor cells developing resistance to anticancer drugs as they can enter the cells without triggering the p-glycoprotein (P-gp) system in the cells that pumps out those drugs. Many anticancer drugs, such as doxorubicin and dexamethasone, were administered successfully using NPs.
NP-Based Drug Delivery Systems can Improve Therapeutic Outcomes of Pancreatic Cancer
NP-based drug delivery systems are specifically more effective against pancreatic cancer, which is highly resistant to radiation and chemotherapy. An in vitro study demonstrated that several anticancer agents, such as sulforaphane and aspirin, are more effective in controlling the growth of pancreatic cancer cells in NP form compared to free form.
For instance, a combination of gemcitabine/ paclitaxel (GEM/PTX) anticancer agents delivered by a mesoporous silica NP (MSNP) drug delivery mechanism displayed more effectiveness in mice with PANC-1 xenografts compared to free GEM plus nab-PTX or GEM, while curcumin (CCM)/PTX co-bounded with albumin (Alb)-NPs successfully prevented the growth of primary tumor without showing systemic or local toxicity, indicating the in vivo safety and efficacy profile of the NP-drug delivery system.
Role of Nanotechnology in Early Diagnosis Progression and Development
In addition to the NP-based pancreatic cancer treatments, a significant effort has been devoted to exploring early detection biomarkers in pancreatic cancer to increase the cure rate.
The progressive manner of epigenetic changes from PanIN-1, PanIN-2, PanIN-3 to invasive cancer was already discovered. Thus, the cancer cure rate can be increased by discovering the early detection biomarker that indicates the transition between the PanIN-3 and the invasive cancer stage.
The promoter DNA methylation of ADAM metallopeptidase with thrombospondin type 1 motif 1 (ADAMTS1) and basonuclin-1 (BNC1) can act as potential biomarkers that can help in optimizing patient prognoses, improving the rates of survival, and early diagnosis of pancreatic cancer. Additionally, innovative methods are being developed using blood-NP interactions to improve cancer staging accuracy.
Overall, this study reviewed the pancreatic cancer pathology, clinical challenges associated with pancreatic cancer therapy, and the increasing significance of nanotechnology and early detection markers for pancreatic cancer treatment and diagnosis. However, more research is required to identify effective and reliable treatment and screening options for pancreatic cancer to improve the overall prognosis and reduce patient mortality.
Sau, S., Iyengar, D., Tatiparti, K. et al. (2022) Nanomedicine for overcoming therapeutic and diagnostic challenges associated with pancreatic cancer. Drug Discovery Today https://www.sciencedirect.com/science/article/pii/S1359644622000903?via%3Dihub