Pancreatic cancer is one of the worst malignancies and the majority of patients discover too late for curative surgery. Even in individuals who have had a curative resection, the disease return rate is more than 80% within two years. Since 1997, when a randomized phase III study showed that gemcitabine monotherapy relieved cancer-related symptoms more than 5-fluorouracil medication; systemic gemcitabine-based chemotherapy has been standard therapy for patients with advanced pancreatic cancer. Researchers and doctors have undertaken many attempts over the last decade to enhance the overall survival of patients with this disease; by combining gemcitabine with another cytotoxic drug. The majority of these gemcitabine combination treatments, however, have failed to provide significant survival benefits above gemcitabine monotherapy.
As a result, a patient needs novel techniques outside just adding more cytotoxic chemicals to gemcitabine. When choosing palliative chemotherapy, it’s also vital to assess the balance between efficacy and quality of life. Curcumin in preclinical in vitro and in vivo investigations; it shows numerous pharmacologic effects such as antioxidant, anti-inflammatory, and anticancer actions; via regulating multiple signalling pathways in different forms of cancer, including pancreatic cancer.
Many researchers want to develop curcumin as a chemopreventive as well as a chemotherapeutic medication due to its promising outcomes. Curcumin has low toxicity compared to traditional cytotoxic medications, which often include side effects such as nausea, vomiting, and exhaustion. This is a significant benefit for treating patients with pancreatic cancer; who, due to their poor clinical circumstances, have a low tolerance for rigorous therapy. Another benefit of this agent is its safety. The Food and Drug Administration and the World Health Organization themselves confirm curcumin’s safety. Factually, people have used it in traditional medicine for thousands of years.
Curcumin shows the possession of anti-cancer properties in preclinical studies; not only against pancreatic cancer but also on other malignancies; which includes breast, colon, stomach, head and neck, hepatic, ovarian, lung, and prostate cancers, as well as lymphoma and leukemia. Lan Li and colleagues were the first to discover curcumin’s anticancer properties in pancreatic cancer cells. Curcumin inhibits nuclear transcription factor-kappa B (NF-B); which inhibits tumour growth in pancreatic cancer cell lines in a time and dose-dependent way.
Researchers also used an orthotopic mouse model of pancreatic cancer to illustrate curcumin’s effectiveness. Despite the fact that either curcumin or gemcitabine had only minor anticancer effects; the combination of the two agents inhibited tumour growth more effectively than either agent alone. Curcumin is present in preclinical tests to enhance the effects of other cytotoxic drugs such as cisplatin, oxaliplatin, and 5-fluorouracil, in addition to gemcitabine. Curcumin has been shown in studies to suppress the expression of microRNA 21, which is overexpressed in a number of cancers, including pancreatic cancer, and is thought to be an oncogenic microRNA.
Navneet Dhillon and colleagues were the first to report on the effects of curcumin on pancreatic cancer in a phase II clinical trial. This study included twenty-five patients, three of whom were chemo-naive. One patient had a stable disease course for almost 18 months; and another patient had a partial response in a liver metastasis (73 percent reduction in size); albeit these effects only lasted one month. According to research, curcumin medication is safe in patients with pancreatic cancer, with no harm linked to curcumin consumption.
IN CLINICAL TRIALS, THE USE OF A HIGHLY BIOAVAILABLE FORM OF CURCUMIN (THERACURMIN®)
Several researchers have investigated plasma curcumin levels in clinical trials, and the majority of them found that despite multi-gram dosages of curcumin, plasma curcumin levels remained low. Due to curcumin’s limited absorption, oral dosages of curcumin did not result in additional rises in plasma curcumin levels in humans in several investigations. As a result, researchers have made various efforts to increase the bioavailability of this substance utilising a number of ways, including the development of novel curcumin analogues and unique drug delivery systems. For example, it has been demonstrated that a nanoparticle-based drug delivery system can increase the water solubility of hydrophobic drugs like curcumin and various distinct forms of nanoparticle-based curcumin.
THERACURMIN® is one of the new varieties of nanoparticle-based curcumin. In rat models, THERACURMIN® revealed a higher than 30-fold increase in bioavailability above traditional curcumin. Ingestion of THERACURMIN® can result in higher plasma curcumin levels than ordinary curcumin, according to a study. As a result, curcumin can be considered a promising method for investigating the anticancer benefits of curcumin in clinical trials, and a follow-up study was done to test the safety of THERACURMIN® in pancreatic cancer patients.
Curcumin has been demonstrated to have anticancer effects in preclinical animals, both alone and in combination with other anticancer medicines, via modulating a range of molecular targets. Curcumin’s limited bioavailability, on the other hand, has been a key barrier to its clinical use. The introduction of highly bioavailable versions of curcumin (THERACURMIN®), which can cause larger plasma curcumin levels without increasing toxicity, has now remedied this problem. We will require more clinical trials to explore the therapeutic potential of this intriguing drug in patients with pancreatic cancer.