Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.
If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.
This week’s study is…
Dual stromal targeting sensitizes pancreatic adenocarcinoma for anti-programmed cell death protein 1 therapy
We previously published about this research in a story titled “A Novel 3-Step Treatment Improves Pancreatic Cancer in Mice Models” which can be found here. The study was originally published in the scientific journal Gastroenterology. You can read the abstract of the study here.
This research team was affiliated with Johns Hopkins University and Cedars-Sinai Cancer.
What Happened?
The researchers sought to conduct a preclinical study on a possible treatment for pancreatic cancer, which is one of the most deadly and difficult to treat forms of cancer. Pancreatic cancer can be highly resistant to many common cancer approaches, such as chemotherapy. The team was specifically targeting pancreatic adenocarcinoma, which is the most common type. The goal with this treatment was two-fold: to disrupt the tumor microenvironment and prevent the cancer from metastasizing (spreading to other areas).
For this study, the scientists used a mouse model of pancreatic cancer. The treatment itself entailed three different components: a protein called FAKi, an anti-PD-1 immunotherapy antibody, and a novel pathway known as CXCR4. The treatment was able to bolster the immune system of the mice, as well as eliminate the pancreatic cancer tumor’s outer microenvironment. Furthermore, it was able to successfully attack the tumor.
In comparison to placebo, the treatment was able to extend the lifespan of the mice and successfully prevented metastasis of the cancer. Overall, this preclinical trial appears to have found a treatment method that successfully disrupts the cancer microenvironment and enables immunotherapy to have a greater treatment effect on the disease.
About Pancreatic Cancer
Pancreatic cancer is one of the most dangerous forms of cancer. The disease affects the pancreas, which is a glandular organ that is situated behind the stomach. Part of the reason that pancreatic cancer is so dangerous is that it rarely produces noticeable symptoms until it has reached an advanced stage and begun to spread. However, even when detected earlier, it is difficult to treat effectively. Risk factors for pancreatic cancer include being male, old age, African-American ancestry, family history, smoking, obesity, diabetes, chronic pancreatitis, and a diet heavy in red meat, processed meat, or meat cooked at very high temperatures. Symptoms include depression, upper abdominal pain, jaundice, diabetes, constipation, weight loss, and appetite loss. Treatment approaches for this cancer include surgery, chemotherapy, and radiation therapy. Even with heavy treatment, pancreatic cancer almost always returns. The five year survival rate is just ten percent. To learn more about pancreatic cancer, click here.
Why Does it Matter?
Pancreatic cancer is a devastating diagnosis to receive, as this cancer has a very low rate of long term survival and is often very aggressive. While only around 62,000 people are anticipated to be diagnosed this year with the disease in the US, pancreatic cancer is anticipated to be the second-leading cause of cancer death in the US by 2030. This highlights the cancer’s deadly nature.
Therefore, the encouraging results from this study are a cause for optimism. The tumor microenvironment in this cancer has long been believed to be part of the reason why pancreatic cancer can be so unresponsive to treatment. Even treatments of the immunotherapy class have had only a limited benefit; but these findings highlight an approach that increases the effectiveness of immunotherapy.
“This is an important step for a disease that is extremely challenging to treat and has very low survival rates…by focusing on the difficult-to-treat tumor microenvironment, we were able to amplify an immune response while simultaneously attacking cancerous cells.” – Arsen Osipov, MD, program lead, Pancreatic Cancer Multidisciplinary Clinic and Precision Medicine Program, Cedars-Sinai Cancer, senior and corresponding author
The scientists anticipate that further research into targeting the microenvironment will continue, and the promising results from this study suggest that this step could be a vital part of treatment.
“This innovative research study emphasizes how simultaneously targeting both intracellular and extracellular components of the microenvironment may improve an immunotherapy response.” – Dan Theodorescu, MD, Ph.D., director, Cedars-Sinai Cancer
The next step will be the development of a clinical trial to evaluate this three-part treatment approach in human patients and determine the potential of the CXCR4 pathway.
