Pancreatic Cancer

Pancreatic Cancer

By Chyler and Olivia Katona and Yingling Yang

Causes

Pancreatic cancer can be caused by carcinogens such as tobacco, and is increased by several risk factors. These include increased age (most commonly over 45), being male or black, smoking, diabetes, and having a diet high in fats. About 25% of pancreatic cancer cases are thought to be caused by tobacco smoking.Pancreatic cancer can also be caused genetically. It can be caused by a mutation in the KRAS gene, which is found on the short arm of chromosome 12. However, there are many genes that are involved in the cell cycle and could potentially cause pancreatic cancer due to mutations. Some other genes known to be linked to pancreatic cancer are BRCA1, BRCA2, PALB2, CDKN2A, ATM, TP53, STK11, MLH1, MSH2, MSH6, PMS2, EPCAM, p16/CDKN2A, TP53, and SMAD4/DPC4.

Environmental

Genetic

KRAS gene

What does it do?

KRAS is an oncogene that codes for instructions on making a protein called K-Ras. K-Ras is part of the RAS/MAPK signaling pathway. It relays signals from outside a cell to the nucleus of the cell. These signals instruct the cell to either continue to grow and divide, or mature and differentiate into a cell with specialized functions.

KRAS stands for Ki-ras2 Kirsten rat sarcoma viral oncogene homolog.

What happens when it mutates?

When there is a mutation in KRAS, it signals too much and cells grow without being told to. This causes the mass of cells known as a tumor. The cancerous tumor grows larger in the pancreas, and can also spread to other parts of the body.

Model of the K-RAS protein

Symptoms

• Severe abdominal pain
• Smaller appetite
• Weight loss
• Jaundice
• Lightly-colored stools
• Darker-colored urine
• Itchy skin
• New diabetes or more uncontrollable diabetes
• Blood clots
• Fatigue

Early symptoms

• Yellowish skin (jaundice)
• Weakness
• Loss of appetite
• Fever
• Nausea
• Unexplained weight loss

Later symptoms

Symptoms usually do not appear until after the cancer is fairly advanced and has spread to other organs. This makes it hard to detect the cancer while it is still curable.

Treatments

Whipple Surgery

Whipple surgery can be used for patients that only have cancer in their pancreas. In the surgery, the head of the pancreas is removed, as well as the duodenum (first part of small intestine), the gallbladder, and the bile duct. However, artificial insulin injections and digestive enzymes will be needed for the rest of the person’s life since the pancreas will not be able to produce them if removed. The Whipple procedure is the only known cure for most pancreatic cancers and tumors. Only 9% of patients have pancreatic cancer diagnosed in these early stages. Whipple Surgery has several risks that should be considered. One concerning one is that even hospitals that frequently perform these surgeries can have a mortality rate of 4%. Less experienced hospitals have even higher rates. Also, patients are at risk to develop diabetes, as the remaining parts of the pancreas may not be able to produce enough insulin.

Radiation

Radiation treatment is the use of radiation to destroy cancer cells, such as through high power x-ray machines. Types of radiation treatment for pancreatic cancer include the traditional version, Stereotactic body radiation (SBRT), also known as cyberknife, and proton beam therapy. The main difference between the three is the method of introducing the radiation to the cancerous cells, and the duration of time during which the body is exposed to the radiation. Medical devices required include machines used as an external source of radiation.

Treatments (cont)

Chemotherapy

Chemotherapy can be used to destroy the cancerous cells through the use of drugs. Patients receive one or more approved drugs on a set schedule to stop the cancerous cells from dividing and multiplying. For pancreatic cancer, the FDA has approved the following drugs for chemotherapy: Capecitabine (Xeloda), Fluorouracil (5-FU), Gemcitabine (Gemzar), Irinotecan (Camptosar), Leucovorin (Wellcovorin), Nab-paclitaxel (Abraxane), Nanoliposomal irinotecan (Onivyde), and Oxaliplatin (Eloxatin). Patients using this method can generally go about their day to day lives with little change or side effects. If using more than one drug, side effects are more common. First treatments are called ‘first line’. If those fail, ‘second line’ treatments are administered. In more difficult cases, doctors may recommend off-label use, where drugs that are approved for other cancers are used, though there is often research stating that a certain drug may work. Side effects for all three types are varied, even for those taking the same drug. Chemotherapy is also used in addition to other treatment methods, such as before or after a surgery.

Studies from December of 2022 at the Penn Pancreatic Cancer Research Center show promise of a new “molecule inhibitor” that works with the immune system to target the gene mutation that causes the cancer. The treatment is considered a “strong candidate” for clinical trials, to increase research on the new treatment. The treatment is meant for those with a KRAS gene mutation, which includes about 90% of pancreatic cancer patients. The treatment mentioned above does not guarantee results, and tumors sometimes return after treatment. Scientists are considering ways to combine medicines so that the tumors cannot come back.

New treatments

Prognosis

“If the cancer is detected at an early stage when surgical removal of the tumor is possible, the 5-year survival rate is 42%. About 13% of people are diagnosed at this stage. If the cancer has spread to surrounding tissues or organs, the 5-year survival rate is 14%. For the 52% of people who are diagnosed after the cancer has spread to a distant part of the body, the 5-year survival rate is 3%.” -American Society of Clinical Oncology

The average 5-year survival rate is 8% (with good treatment). People that can have surgery have a survival rate of 15%. If the cancer is locally advanced and unresectable (it cannot be surgically removed and is advanced but still only in the pancreas) there is a 8-12 month survival rate.

Why is the survival rate so low?

In most cases, pancreatic cancer is not discovered until it is in its later stages or has spread to other areas of the body, after which it becomes very hard to treat. This is because the symptoms often do not appear until the cancer is advanced. People often are not able to detect symptoms in the earlier stages, when they would have a higher chance of survival.

The Whipple procedure is a major, complex surgery that has risks such as infection and people already in poor health may choose not to take the risk by undergoing the procedure.

Risks of treatment

Chemotherapy is physically debilitating and can cause long-term damage to nerves as well as vital organs like the heart and lungs. Some chemo drugs can also cause other types of cancers. Radiation is a carcinogen itself and can actually increase the risk of cancer development if it is used. Radiotherapy and chemotherapy kill healthy cells as well as cancerous ones, putting the body under even more stress.

Blood can be tested for proteins called tumor markers that are shed by the cancer cells. A CA 19-9 test measures the amount of CA 19-9 protein (cancer antigen 19-9) in a sample of blood. A sample of blood is tested for CA 19-9. In healthy people there is very little CA 19-9 in the blood, but in people with pancreatic cancer there are high levels of it. Percutaneous biopsies are usually used for pancreatic cancer. A thin hollow needle is inserted through the skin and into the pancreas, removing a small part of the suspected tumor for examination.

Blood testing

Diagnosis

Biopsy

MRI, CT, ultrasound or PET scans can also be used to take images of the pancreas and look for tumors.

Normal vs Cancerous pancreas cells under a microscope

Cancer cells in the pancreas are often surrounded by dense, fibrous scar tissue called stroma. The stroma forms most of the tumor, with as little as 10% of the tumor being composed of cancer cells. The stroma makes the tumor extremely hard and is a barrier to cancer drugs. It is also thought to play a role in drug resistance and cancer development.

Links used:

https://www.cancer.net/cancer-types/pancreatic-cancer

https://pancan.org/facing-pancreatic-cancer/about-pancreatic-cancer/risk-factors/genetic-hereditary/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666336/

https://www.cancer.net/cancer-types/pancreatic-cancer/statistics

https://www.hopkinsmedicine.org/health/conditions-and-diseases/pancreatic-cancer/pancreatic-cancer-prognosis

https://www.uptodate.com/contents/supportive-care-of-the-patient-with-locally-advanced-or-metastatic-exocrine-pancreatic-cancer/print

https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/pancreatic-cancer/survival

https://www.mayoclinic.org/diseases-conditions/pancreatic-cancer/diagnosis-treatment/

https://www.cancer.org/cancer/pancreatic-cancer/treating/chemotherapy.html

https://www.pennmedicine.org/news/news-releases/2022/december/study-shows-promise-of-new-anti-kras-drug-for-pancreatic-cancer

https://www.cancer.org/cancer/pancreatic-cancer/detection-diagnosis-staging/staging.html

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963227/