Pancreatic Cancer Research Projects
MOON SHOTS PROGRAM
Pancreatic Cancer Priority Projects
Research projects of the Pancreatic Cancer Moon Shot® address the crucial issues facing pancreatic cancer patients by focusing our largest efforts on the approaches that have near‐term measurable success. Our efforts are aimed at developing new therapeutic strategies, enhancing outcomes by administering therapy prior to surgery and designing sophisticated methods to detect pancreatic cancer earlier.
Pancreatic cancer is highly metastatic and often chemo-resistant. The Pancreatic Cancer Moon Shot® team is taking a multi-prong approach to develop novel therapies to increase the overall survival of our patients. Over 90% of pancreatic cancer patients have genetic abnormalities in a specific gene called KRAS. We’ve developed a way to silence these abnormalities using a novel delivery system called “iExosomes.” We’re also developing targeted therapies that inhibit recurrently abnormal genes and pathways in pancreatic cancer, investigating how to adapt immunotherapy into a treatment option for this disease and developing a liquid biopsy to personalize patient treatment.
Recent sequencing efforts have helped clarify the genomic landscape of pancreatic ductal adenocarcinoma (PDAC) and reaffirmed that it is dominated by alterations that are considered “undruggable.” For instance, developing a drug that specifically inhibits KRAS mutations has proven to be challenging. We are developing and evaluating novel therapeutic approaches to take aim at pancreatic cancer from several vantage points.
In many diseases like melanoma or lung cancer, immunotherapy, which turns the body’s immune system against the cancer cells, has shown dramatic effects on survival. Unfortunately, many of these drugs have failed to benefit pancreatic cancer. We are investigating how to develop immunotherapy into a viable treatment option for pancreatic cancer patients by focusing on turning the primary immune cells in the body, called T cells, into more powerful cancer killers. We’ve successfully isolated T cells from patients and increased their activity in the laboratory. We then re-inject large volumes of these powerful immune cells back into patients to more effectively fight their tumor. A clinical trial is observing if this technology will generate a significant response. In addition, we’ve identified several tumor signatures that are shared between pancreatic cancer patients. These shared signatures can then be used to engineer T cells to better recognize pancreatic cancer tissue at a more universal level. These “off-the-shelf” T cells can then be used to treat any patient, and could make a significant impact in the clinic.
We’re also addressing the challenging and potentially risky nature of tissue biopsy collection and analysis. Our novel liquid biopsy program enables the complete genomic characterization of every patient’s tumor using only a single vial of blood. This technology places us in a unique position to “match” patients to the best trial without the need for them to undergo invasive tissue biopsies. This personalized program operates in collaboration with the Moon Shots Program's APOLLO platform and the information collected from this study will guide drug development and allow clinicians to track a patient’s response to therapy.
Many pancreatic cancer patients who have localized disease will undergo surgery to have their tumor removed. MD Anderson Cancer Center has shown that patient survival outcomes improve if prior to surgery they are treated with drugs or radiation. This pre-surgical treatment is called neoadjuvant therapy. In fact, the median overall survival for pancreatic cancer patients that successfully complete neoadjuvant therapy and surgical resection at MD Anderson is 43 months, which is nearly double the national average.
The goal of the Pancreatic Cancer Moon Shot's neoadjuvant platform is to evaluate novel therapeutic agents in the neoadjuvant setting to enhance resectability and survival in our patients. We have conducted a series of trials geared towards patients with resectable, borderline resectable or locally advanced disease. Each trial was accompanied by extensive blood- and tissue-based analysis, including long-term monitoring, in order to unravel the underpinnings of response and resistance to particular treatments.
There is clear evidence that diagnosis of pancreatic ductal adenocarcinoma (PDAC) at earlier, resectable stages has a profoundly favorable impact on disease prognosis. To detect pancreatic cancer earlier, we’re using three parallel efforts:
- Analysis of patient samples to define tumor signatures that can be used in a blood-based biomarker test to uncover early-stage PDAC
- Developing advanced, quantifiable imaging tools and methods to identify early and progressive neoplasia
- A multi-disciplinary clinic for individuals at high risk for pancreatic cancer
As leaders in this area, we’ve already made significant progress in our efforts to create a blood test for pancreatic cancer. Our three-protein biomarker panel has been substantially validated and we’re optimistic that it will have an impact on early detection of this disease. Now, we’re refining our panel and aiming to improve its performance by adding additional biomarkers. We’ll then test this blood-based biomarker panel in asymptomatic pre-diagnostic settings, including our high-risk clinic. Once fully-tested, our intent is to use this blood test as an early detection mechanism for both high-risk (those with familial PDAC, new-onset type 2 diabetes and chronic pancreatitis) and general populations.
Our Moon Shot team recognizes that once a sensitive and specific blood test is developed we’ll need sophisticated imaging techniques to determine the location of the disease so that it can be managed appropriately. To address this, we’re developing an image processing method called enhancement pattern mapping (EPM) that enables detection of small volume pancreatic tumors by amplifying abnormal signals that are usually undetectable.
The chance that a healthy adult in the general population will develop PDAC is approximately 1 in 10,000. However, individuals with an inherited predisposition to PDAC present a unique opportunity for screening and early diagnosis at an asymptomatic stage. To offer this service to such individuals, we’ve initiated Houston’s first Pancreatic Cancer-High Risk Clinic (PC-HRC). This clinic will track patients through biospecimen collection and help inform and validate our blood-based biomarker and EPM imaging method.