Pancreatic Ductal Adenocarcinoma and its Treatment Strategies

Aiman Yaseen1, Muhammad Akram1, *

1Department of Life Sciences, School of Science, University of Management and Technology, Lahore, 54770, Pakistan

*Corresponding Author:

Introduction

Drug discovery and development through different technologies and strategies has addressed multiple diseases such as Alzheimer’s disease, Parkinson’s disease, many viral diseases and multiple types of cancers such as prostate cancer, ovarian cancer, breast cancer, lung cancer, pancreatic cancer and many more. This review aims to discuss the biology and treatment strategies for pancreatic ductal adenocarcinoma.

Physiology of Pancreas

This is an organ present behind the stomach surrounded by other organs. It has a major role in digestion, comprises of enzymes like amylase, trypsin and lipase. It is made up of two glands endocrine and exocrine glands.

Literature Review

Proteins over-expresses during PDAC

There are multiple novel tumor specific proteins, genes or antigens which are crucial for the point of view of therapeutic applications in PDAC. Here in this review, a few proteins are being discussed, their function, importance in the progression of PDAC.

Leukemia Inhibitory Factor (LIF)

Nima –related protein kinase -7 (NEK-7)

Phosphoprotein Phosphatases family (PPPs)

Kallikrein –related protein -8 (KLK8)

KLK8 is also an important protein which over-expresses during PDAC. Over-expression of this protein cleaves epidermal growth factor (EGF), then binds to epidermal growth factor receptor (EGFR) and start multiple signaling pathways associated with the progression of PDAC.

Treatment Availability of PDAC

Non- oncology Drugs for PDAC

Figure 2. Microenvironment of Pancreas

Drugs obtained through Virtual Screening

Chemotherapy

Surgical Treatment

Combinational Therapies

Immunotherapy

An advanced type of cancer treatment is immunotherapy. Tumor microenvironment (TME) consists of different types of cell populations, which include dendritic cells, (CAFs) cancer associated fibroblasts, epithelial cells, T-regulatory cells, tumor associated macrophages (TAM), and B-lymphocytes. They show intrinsic resistance to conventional treatment that is use of chemotherapeutic drugs. Several types of immunotherapies reported such as use of monoclonal antibodies, immune checkpoint inhibitors, adoptive cell transfer and vaccination.

Nanotechnology based drug delivery system (DDS)

Personalized Medicines

There are some limited regarding the treatment strategies of PDAC. Prior, only gemcitabine was used. Some other combinations were also used but there are some limitations in using these drugs as combinational therapies. Some non-oncology drugs, in-silico identified drugs are also available but they lack in-vivo and in-vitro experimentations for proper validation to be used as a treatment against PDAC. Personalized medicines have some limitations too. They will target specific mutation or specific biomarkers. It means huge amount of funds are required for designing medicines for other mutations or genes which are leading towards PDAC. Advanced treatment such as nanotechnology based drug delivery system (DDS) has outperformed conventional treatment in clinical trials. But it also require further research to develop formulations that target every specific mutation. This requires a lot of research to explore the unidentified and unexplored areas.

Conclusion

Progress in the treatment of PDAC is ongoing and survival rate has been increased from 5% to 9% from the last few years. Since 1996, the treatment against PDAC has started and emerging day by day that will improve the outcome of the disease to overcome it. But gemcitabine and combination of different drugs has not shown survival benefit. Combination use of monoclonal antibodies and immune checkpoint inhibitors have shown proven results yet. Still, there is an urgent need to develop strategies that would discover specific and sensitive biomarkers for rapid identification. There is a need to conduct more pre-clinical and clinical studies to explore the efficacy of different treatments. Advanced treatments such as immunotherapy, personalized medicines and nanotechnology based drug delivery system has revolutionized the field of drug development and discovery that will target the specific genes and receptors, ultimately stop the signaling pathways and hence alleviate disease progression. There is a need to collaborate with different oncologist, pharmacists, radiologist and surgeons to design the accurate patients’ classification for proper treatment at proper time. Research is needed to further explore the best treatment in the recent years to combat this lethality.

Funding: This study did not receive any funding in any form.

Acknowledgments: This study conducted and supported by the Department of Life Science, University of Management and Technology, Lahore, Pakistan.

Conflicts of Interest: The authors declare no conflict of interest

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