Pancreatic Cancer Vaccine: The Future of Treatment?
According to the National Cancer Institute, an estimated 51,750 Americans will die of pancreatic cancer (PC) in 2024. As such, patients face an unprecedented 12.8% 5-year survival rate, making pancreatic cancer one of the deadliest forms of this disease.
To comprehend the inadequacies of current treatment options, it is important to understand the complexities of the disease. The pancreas itself is an important organ. It produces crucial hormones like insulin and glucagon, both of which are necessary for the regulation of blood sugar levels. Additionally, it is responsible for food digestion through the release of enzymes from the exocrine glands. The most common type of pancreatic cancer is Pancreatic Ductal Adenocarcinoma, which makes up 95% of all diagnoses according to the American Cancer Society. This type occurs when exocrine cells, which compose exocrine glands and ducts, begin to form at rapid rates. As the pancreas is located behind the stomach and close to the spine, this cell growth is often hidden from practitioners.
However, this is just one issue surrounding early detection. Pancreatic cancer is often called a silent disease, as it fails to present symptoms in early stages of development. In fact, symptoms often remain invisible until the cancer has spread to other organs, thereby reducing the effectiveness of treatment options. Even after symptoms begin to appear, they generally remain mild. Examples include belly pain, specifically on the side, loss of appetite, itching, tiredness and weakness. As symptoms worsen, patients may experience jaundice and discoloration of urine and stool in addition to the development of diabetes. While the cancer is inevitably detected, the long pre-symptomatic phase allows for the rapid growth of exocrine cells and the formation of tumors. As such, Gheorghe et al. explains that 75% of patients get diagnosed in stage III to IV, when resection surgery is an impossibility.
While diagnosis is difficult, several factors put individuals at risk of pancreatic cancer. These may include smoking and drinking, type 2 diabetes, pancreatitis, and a family history of PC. Another factor includes genetic mutations in DNA, including the BRCA2 and CDKN2A genes. As trends indicate these as primary risk factors, many current solutions involve early screenings of patients that fall under these categories. Testing options include imaging tests, like an ultrasound and MRI, and genetic testing. The goal of such screening techniques is to catch the cancer while it is small and easily treatable. However, simply scanning at risk individuals produces ineffective results as PC is a rare form of cancer. This means that the majority of those tested will receive negative results.
The most effective cure to pancreatic cancer is tumor removal surgery. However, palliative surgery is sometimes conducted to remove sources of pain and increase quality of life. Additional treatments include radiation therapy, chemotherapy, and chemoradiation therapy.
However, given the high mortality rates of PC, medical professionals are continuing to search for more effective treatment and diagnostic processes. Diagnostic research is being conducted on AI as a detection tool, which would utilize patient risk factors and other data to identify individuals at the most immediate risk of developing PC. Nonetheless, scholarly focus has centered around the development of more effective treatment options, as limited treatment options once the cancer is inoperable has largely shaped the current mortality rate.
This has led to the development of a possible pancreatic cancer vaccine. Several variations of the vaccine are being clinically trialed. However, the goal of all of the vaccines is the same. They intend to serve as a treatment option to PC, both after operation and for inoperable tumors. All vaccines intend to alert T-cells, a type of white blood cell known as a lymphocyte which fights off infection, of cancerous growth. T-cells themselves need to be activated or alerted of an issue in the immune system before they respond. However, cancer cells have found a way to trick T-cells into not recognizing them as a threat, thereby preventing T-cells from activating a response to the cancer growth. By finding a way to alert T-cells, researchers hope that the widespread growth of pancreatic cancer cells will be severely limited, thereby providing a more effective treatment plan than current available options.
The first form of vaccination tested against pancreatic tumors were peptide and protein-based. These are intended to target mutations present in the majority of pancreatic cancer cells, thereby stimulating an anti-tumor T-cell response. Vaccines would target mutations like KRAS, Telomerase and Gastrin. While trials were somewhat successful, additional research must be conducted to determine the true impact of this form of vaccines and their level of safety.
As there are several ways to activate T-cells, clinical trials have focused on different variations of the vaccine. A trial conducted by Lei Zhang, a medical oncologist at Johns Hopkins University, used a vaccine composed from inactivated tumor cells. In testing, some patients' immune systems responded to the vaccine, which prompted an attack on cancer cell growth, both in the pancreas and in areas cells had spread to. However, the testing done by Zhang was very limited and more investigation needs to be done to determine the effectiveness of this vaccination in comparison to other forms, like peptide and protein-based vaccines.
Another variation, known as the Investigational mRNA Vaccine, aims to accomplish a similar goal. This vaccine is custom-made for all individuals participating in the trial based on the mutational profile of their tumor. The vaccine aims to teach T-cells to recognize neoantigens, or proteins present in their pancreatic tumor. Thereby, the T-cell can recognize the cancer as a foreign invader and activate a response. In the initial trial, 50% of the patients responded to the vaccine. Of these patients, each experienced the activation of around 98% of T-cells, an incredibly successful result. Due to high success, a secondary trial is being conducted with a larger sample size and a control group to better determine the future of the vaccine.
Ultimately, the prospect of effective pancreatic cancer vaccines is hopeful. Many clinical trials have demonstrated optimism towards the future of the technology. However, vaccines safe for human trials have only been created recently meaning minimal studies have been conducted. A large sample size for testing and investigation is necessary before this innovation can be approved for widespread use. Even after approval, many professionals argue that vaccination should be used alongside other treatment options, including chemotherapy and radiation therapy. This would provide the optimum treatment for patients with inoperable tumors. Additionally, some even believe vaccination could occur following surgery as a means to prevent recurrence.
As such, the continued innovation in the field of pancreatic cancer diagnosis and treatment is crucial to lowering mortality rates and increasing early detection options. The development of a widespread pancreatic vaccine could influence cancer technology across all forms, thereby expanding its impacts. It is an exciting new prospect in the oncology community and should be followed closely in the upcoming years.
Works Cited
"Cancer Stat Facts: Pancreatic Cancer." National Cancer Institute, edited by American Cancer Society, U.S. Department of Health and Human Services, 2024, seer.cancer.gov/statfacts/html/pancreas.html. Accessed 18 Dec. 2024.
Gheorghe, Gina. "Early Diagnosis of Pancreatic Cancer: The Key to Survival." Diagnostics, 24 Oct. 2020, pmc.ncbi.nlm.nih.gov/articles/PMC7694042/#:~:text=One%20of%20the%20most%20effective,sensitivity%20and%20a%2099%25%20specificity. Accessed 21 Dec. 2024.
"Pancreatic Cancer." American Cancer Society, 2024, www.cancer.org/cancer/types/pancreatic-cancer.html. Accessed 18 Dec. 2024.
"Pancreatic Cancer." Mayo Clinic, Mayo Foundation for Medical Education and Research, 4 May 2024, www.mayoclinic.org/diseases-conditions/pancreatic-cancer/symptoms-causes/syc-20355421#:~:text=Pancreatic%20cancer%20is%20a%20type,cancer%20is%20pancreatic%20ductal%20adenocarcinoma. Accessed 21 Dec. 2024.
"Pancreatic Cancer Treatment." National Cancer Institute, National Institute of Health, 2024, www.cancer.gov/types/pancreatic/patient/pancreatic-treatment-pdq#_162. Accessed 21 Dec. 2024.
Salman, Bulent, et al. "Vaccine Therapy for Pancreatic Cancer." Taylor and Francis, vol. 2, no. 12, 22 Oct. 2013, www.tandfonline.com/doi/full/10.4161/onci.26662#d1e165. Accessed 21 Dec. 2024.
Stallard, Jim, editor. "Investigational mRNA Vaccine Induced Persistent Immune Response in Phase 1 Trial of Patients with Pancreatic Cancer." Memorial Sloan Kettering Cancer Center, 7 Apr. 2024, www.mskcc.org/news/can-mrna-vaccines-fight-pancreatic-cancer-msk-clinical-researchers-are-trying-find-out. Accessed 21 Dec. 2024.
Zheng, Lei, editor. "Pancreatic Cancer Vaccine: What to Know." Johns Hopkins Medicine, Johns Hopkins University, www.hopkinsmedicine.org/health/conditions-and-diseases/pancreatic-cancer/pancreatic-cancer-vaccine-what-to-know. Accessed 21 Dec. 2024.