Pancreatic Cancer Research Projects

Development of innovative therapies

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, KRAS mutations are present in up to 90% or more pancreatic cancers, yet developing a drug that specifically inhibits this abnormal tumor-specific signature has proven to be challenging. The Pancreatic Cancer Moon Shot™ team is developing and evaluating novel therapeutic approaches to take aim at pancreatic cancer from several vantage points.

To target KRAS-driven pancreatic tumors, we’ve developed a unique technology called “iExosomes” to silence abnormal KRAS activity. In collaboration with the Adoptive Cellular Therapy Moon Shot™ platform, we’re validating our preclinical findings in a variety of models and beginning Investigational New Drug (IND) enabling studies required by the FDA with the intent of bringing this treatment approach to a pilot clinical trial for pancreatic cancer patients.

In addition, we’re collaborating with the Institute of Applied Cancer Science (IACS) and Center for Co-Clinical Trials (CCCT) Moon Shot platforms to develop targeted therapies that inhibit recurrently abnormal genes and pathways in pancreatic cancer. These therapies have been shown to be highly effective in multiple pancreatic cancer preclinical models and several will soon enter Phase I clinical trials for pancreatic cancer.

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. The Pancreatic Moon Shot has been aggressively 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 new clinical trial is currently enrolling patients to observe 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 APOLLO Moon Shot platform and the information collected from this study will guide drug development and allow clinicians to track a patient’s response to therapy.

Early detection through biomarkers and imaging

There is clear evidence that diagnosis of 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 10,0000. 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.