Herbal Medicinal Agents with Gemcitabine in Treatment-Resistant pancreatic cancers: A Promising Area of Research

Pancreatic cancer is one of the most lethal malignancies that accounts for the 3^rd leading cause of cancer related deaths in world. Poor Prognosis, late diagnosis, aggressive invasive nature makes pancreatic cancer a challenging threat to the modern medicinal science. Gemcitabine, a nucleoside analogue is the first line chemotherapeutic agents that has been used in pancreatic cancer patients. Beside gemcitabine, various other chemotherapeutic agents like oxaliplatin, erlotinib, and their combination have been used against the treatment of resistant pancreatic cancer. However, even with various combinational approach and gemcitabine, the response rate of pancreatic cancer against these treatment is very poor (5.4%). In this relentless effort of overcoming resistance of pancreatic cancer towards treatment, use of herbal plants could be significant as various herbal plants have shown promising results in various pre-clinical and clinical studies.

Crude plant extracts or bio-active components of plants like curcumin, shagol, eschin, emodin, piperlongumine, shikonin, colchicine, bitter-melon, capsicum, gedunin, resveratrol, mangositin, microsclerodermin, etc. have shown to reduce tumor volume in in-vitro/in-vivo models of pancreatic cancer. Further-more combinations of these bio-active components with gemcitabine have shown significant reduction of tumor as compared to gemcitabine or plant extracts alone. Mechanisms of increased efficacy towards therapy by these medicinal plants is mainly based on their property to overcome apoptotic resistance of pancreatic tumor. Beside this, common properties of herbal plants like multiple target sites, anti-inflammatory and less side effects make them more promising for the use against treatment resistant pancreatic cancer. Various dietary agents including citrus fruits and plants rich in flavonoid and B-caretinoids are associated with anti-oxidant, anti-inflammatory, pro-apoptotic and anti-proliferation properties. Curcumin- a flavoring agent (spice) commonly used in south Asian countries like India, China, Nepal is known to have anti-cancer properties against various cancer including pancreatic cancer. Importantly two of the phase II clinical trials have shown increased survival rate in patients taking curcumin. Similarly, Ukrain- a semi-synthetic derivative of chelidonine obtained from plant chelidonium majus in a clinical trial has shown improved survival rates in comparison to patients receiving gemcitabine alone.

Various herbal plants are known from centuries for their anti-cancer effects and other medicinal use. However, they have not been suitably explored to bring them for clinical use. No patent right, research difficulties and less funding are some of the reason amongst many for not bringing out the use of herbal plants on commercial scale but should not worth when it comes to cure the fatal ailment like cancer. Regardless of positive outcomes from various pre-clinical and clinical studies future clinical studies are warranted to establish the clinical use of natural agents in treatment of pancreatic cancer.

Reference:

Marasini and Sahu. Natural agents: Implications in gemcitabine resistant Pancreatic cancer. Mini Reviews in medicinal chemistry. 2017, 17, 920-927.

                                                                                        Bishal Marasini

Researcher

Cincinnati Children Hospital Medical Center
MS (Pharmacology)