?The mouth, the stomach, and the intestines.

?The human digestive tract is often viewed as a few simple parts: the mouth, the stomach, and the intestines. There are numerous other, lesser-known organs that play vital roles in the digestive process as well. One of the most important of these organs is the pancreas. It is a small organ the sits just behind the stomach, producing enzymes and hormones to aid in the digestive process. Just like other organs, the pancreas is vulnerable to cancer. While Professor Wilhelm Conrad Roentgen proposed the existence of pancreatic cancer in 1895, it wasn’t able to be proven until 1927. The invention of the x-ray allowed imaging of the abdomen, confirming the existence of pancreatic cancer. Pancreatic cancer is a high risk cancer, but treatments have proven to prolong the lives of those diagnosed with it.    ?The pancreas has two different types of functions: endocrine and exocrine. Its endocrine functions consist of producing insulin and glucagon, which are the primary hormones involved in controlling blood sugar levels. Its exocrine functions consist of creating enzymes to help break down food particles. The primary enzymes are protease, lipase, and amylase, which break down proteins, lipids, and sugars, respectively. These enzymes are released into the stomach and the small intestine, allowing food to be fully broken down so it can be absorbed by the intestines. Without these enzymes the body cannot properly digest food, leading to malnourishment and wasting. This is why pancreatic cancer can be so devastating to the body. Cancer is an umbrella term for over 100 conditions characterized by DNA mutations leading to uncontrolled cell growth, which can lead to tumors and organ failure (Bolesta 1). There are two different types of tumors in pancreatic cancer. Exocrine tumors, also known as adenocarcinomas, are the primary type of tumor found. They often form in the pancreatic ducts before spreading throughout the rest of the pancreas. Neuroendocrine tumors are the other type of tumor found in the pancreas. These are much rarer and are usually benign. There are several different risk factors for pancreatic cancer. These include age, gender, family history, particularly the BRCA2 gene mutation, pancreatitis, and diabetes (“Symptoms” 1).     Pancreatic cancer causes numerous symptoms and complications, including weight loss, jaundice, pain, and bowel obstruction. Weight loss often occurs because the body is unable to process and absorb nutrients without the aid of the major pancreatic enzymes. The location of the tumor inside the pancreas can determine the symptoms that occur. If the tumor occurs in the entrance of the bile duct it can create a blockage that results in the liver being unable to secrete bile. This leads to a buildup of a chemical known as bilirubin, which leads to jaundice, a yellowing of the skin and eyes. The tumor location can also determine whether or not it causes pain. As the tumor grows larger it can begin to press on other organs, causing discomfort and pain. The location can determine which organs it will affect. The growth of the tumor can also press into the walls of the small intestine, causing it to narrow and create a blockage (“Symptoms” 3). Despite these symptoms being very profound, they are often blamed on other potential illnesses. This leads to pancreatic cancer going undiagnosed until it has reached advanced stages. Treatment often comes with its own set of side effects. Chemotherapy and radiation are known for causing changes in taste, constipation or diarrhea, fatigue, hair loss, loss of appetite, hand/ foot syndrome, and lowered red and white blood cell counts (“Side Effects” 1).     Current treatments include surgery, radiation therapy, and chemotherapy. Surgery is typically put into place when the tumor is still small and can be resected. Resection can also be used in late-stage cancer to reduce the size of the tumor and decrease the patient’s pain. Radiation treatments can be used before or after surgery. They are not used for complete suppression of the tumor, but they can help shrink the tumor. This reduces pain for the patient and can help slow the progression of the disease (“Radiation” 1). There are four main chemotherapy agents approved by the FDA for the treatment of pancreatic cancer. These drugs are Abraxane, Gemzar, 5-fluorouracil (5-FU), and Onivyde. Out of these, Gemzar is the most commonly used agent. It was approved in 1996 and has shown to provide clinical benefits and less symptoms than other approved treatments (Heinemann 1). Gemzar works by preventing the replication of DNA in cancer cells, thereby stopping the overall process of cell division. When added to chemotherapy including Gemzar, Abraxane has helped prolong some lives of those who have advanced pancreatic cancer. Abraxane works similarly to Gemzar, interrupting the cancer cells’ ability to divide (“Abraxane plus” 1). If the tumor is caught early enough it is often possible to have it surgically removed. After removal, patients are frequently started on gemcitabine, a chemotherapy agent, to suppress any remaining cancerous cells. Pancreatic tumors are rarely discovered this early, however, so less than 20% of patients are eligible for surgical removal (“Pancreatic” 1). Standard therapy for patients who are unable to undergo surgical resection consists of treatment with gemcitabine. Gemcitabine works by inhibiting DNA synthesis, reducing the rate at which the cancerous cells can multiply (“Gemzar” 1). Treatment with gemcitabine has been shown to prolong life-expectancy by several months, but it has not been shown to fully suppress pancreatic cancer (“Treating” 1). Another chemotherapy drug, 5-fluorouracil (5-FU), was formerly a common agent for pancreatic cancer. Studies showed that gemcitabine is equally effective in the treatment of pancreatic tumors but causes less side effects, so gemcitabine became the standard therapy (Kota 1). Scientists are researching different methods for overcoming the barriers that have so far made pancreatic cancer so difficult to treat. Since one of the largest obstacles in treating pancreatic cancer is getting effective drug concentrations to the active tumor, there is a large focus on finding drugs that can be added to current treatments to enhance their ability to penetrate the tumor site. Another goal of researchers is finding a drug that can work synergistically with current therapy to increase the potency of the drugs and reduce cancer replication. Two drugs that have been recently studied as potential options to improve current chemotherapy regimens are nab-paclitaxel and capecitabine.     Paclitaxel is a chemotherapy agent that works by inhibiting the replication of chromosomes during mitosis, which leads to decreased overall cell replication. Nab-paclitaxel is a form of paclitaxel that has been combined with albumin nanoparticles to improve its ability to penetrate and remain within tumor sites. Albumin has a very high binding affinity for a protein known as SPARC. SPARC is found in very high levels in pancreatic tumors. The albumin that is attached to the paclitaxel is bound by SPARC, pulling the paclitaxel into the tumor site and preventing it from being pulled out. Nab-paclitaxel has also been found to increase the concentration of gemcitabine in the tumor site when the two agents are used in combination (Kota 1). A study published in the New England Journal of Medicine in 2013 showed a significant improvement in survival in patients that were treated with nab-paclitaxel and gemcitabine compared to patients that were only treated with gemcitabine. The survival rate at one year was 35% in the group that was treated with nab-paclitaxel and gemcitabine versus only 22% in the group treated with only gemcitabine. The results were similar at the two year mark, where the group treated with nab-paclitaxel and gemcitabine was 9% versus 4% in the group that was only treated with gemcitabine (Hoff 1). These results show that nab-paclitaxel has a significant impact on pancreatic cancer therapy. There are now trials underway to determine how effective nab-paclitaxel is as monotherapy, as well as trials using it in combination with other chemotherapy agents.    Capecitabine is another chemotherapy agent that is being studied as a potential option for improving the effectiveness of existing treatments for pancreatic cancer. It works by inhibiting the formation of thymidylate, which is a vital ingredient for DNA synthesis. This inhibition of thymidylate results in reduced DNA synthesis, which leads to reduced replication of cancer cells (“Xeloda” 1). It is believed that the effects of capecitabine combined with gemcitabine create a synergistic effect that improves the potency of both drugs. ESPAC-4, a study published in March, 2017, compared the effectiveness of treatment with both capecitabine and gemcitabine to treatment with gemcitabine alone in patients who had already undergone surgical removal of a pancreatic tumor. The study found that the group that was treated with capecitabine and gemcitabine had a median survival rate of 28.0 months compared to 25.5 months in the group that was treated with only gemcitabine (Neoptolemos 1). Future studies are planned to examine the effectiveness of using the combination of capecitabine and gemcitabine for treating patients who did not have a tumor surgically removed.    Pancreatic cancer is the fourth deadliest cancer in the world. Treatments have been proven to be difficult to find. Most treatments do not cure the cancer, only prolong the life of the person who has it. More studies will be performed to find better options with those who have it. New drugs are being found every day. Treatments have been proven to prolong the lives of those diagnosed with pancreatic cancer.