Mazur Labs' work focuses on the identification of novel drug targets that can efficiently treat lung and pancreatic cancers, the two most deadly human malignancies. They are one of the first teams to register for PurpleStride 2022!
Note: This article was edited for the October 13, 2021 issue of The PurpleStrider to fit the space. The article appears here in its entirety.
Meet Team Mazur Labs of MD Anderson
For Pawel K. Mazur, Ph.D, Pancreatic Cancer is personal.
Dr. Mazur, what’s the status of novel targeted drugs and immunotherapies that enable precision medicine clinical trials for cancer patients?
Immunotherapies have been proven to be very successful in liquid tumors and are also a hot topic in the treatment of pancreatic cancer right now. Unlike leukemias and lymphomas, pancreatic cancer is a solid tumor and furthermore characterized by an excessive tumor stroma which displays an immunosuppressive microenvironment that contributes to T cell exhaustion and hence immunotherapy alone is not applicable in pancreatic cancer patients. Currently, there are several clinical trials ongoing/under way that combine immunotherapy with chemotherapy and targeted therapies. The aim of these therapies is to overcome the immunosuppressive tumor microenvironment and consequently prevent T cell exhaustion.
One example of such an approach is a clinical trial that is currently performed at the Sidney Kimmel Comprehensive Cancer Center at John Hopkins. Here, chemotherapy (cyclophosphamide), a checkpoint inhibitor (pembrolizumab), a pancreatic cancer vaccine (GVAX) and an inhibitor for colony stimulating factor 1 receptor (CSF1R) are combined. CSF1R has shown to contribute to the immunosuppressive PDAC microenvironment by recruiting immunosuppressive tumor associated macrophages to the tumor microenvironment. In preclinical studies inhibition of CSF1R has shown promising effects by reducing the number of tumor associated macrophages, increasing T cell activity and thus ameliorating chemotherapy effects. This therapy is currently in a phase 1 clinical trial.
In parallel there are clinical trials that combine immunotherapy with agents that target the fibrotic stroma in order to inhibit the immunosuppressive microenvironment. For instance, the combination of the checkpoint inhibitor pembrolizumab and the focal adhesion kinase (FAK) inhibitor defactinib are currently investigated in pancreatic cancer patients following chemotherapy in a phase 2 study. The focal adhesion kinase has been reported to be highly expressed in pancreatic cancer patients and to correlate with a stronger stromal reaction evident by higher collagen deposition. Combination treatment consisting of chemotherapy, a checkpoint inhibitor and the FAK inhibitor have shown promising results in preclinical models and are currently tested in a clinical setting.
Furthermore, the development of so-called chimeric antigen receptor T cells (CAR T) which target a specific antigen that is predominantly found on pancreatic cancer cells is being tested in several labs. This novel approach uses the patients’ own T cells which are engineered in the lab to target specific cells and subsequently are reintroduced into the patient. This kind of immunotherapy is still in its infancies in pancreatic cancer but has already been successfully utilized to cure some kinds of lymphomas and leukemias. As for the immunotherapies that are employing checkpoint inhibitors, the major hurdle using CAR T cells in pancreatic cancer patients is the immunosuppressive microenvironment which results in exhaustion of these specialized T cells and consequently renders them ineffective. Researchers in several labs (also in the Mazur lab) are currently working on modifying these CAR T cells in order to reduce exhaustion and keep them in an active state.
Dr. Mazur, what caused to become interested in this area of medicine?
Science is my lifelong passion and I am whole heartedly devoted to a career in human health-oriented research – in particular I am committed to search for the causes and cures for the most devastating human diseases – pancreatic cancer. Pancreatic cancer has had a tremendous impact on my life. My maternal grandfather – my greatest role model, a WWII hero awarded the highest honors, including the Righteous Among the Nations –succumbed to this dismal disease. His courage and selflessness have helped shape my ambition. My research is a tribute to his memory.
How long have you been participating in PurpleStride?
Our lab is participating in PurpleStride since 2019. That’s when I heard the first time about this event. After I told all the lab members about it everybody was excited and we designed our own personalized purple T-shirts that we wore on the PurpleStride 2019. Since then we are planning to participate every year and we are thrilled about PurpleStride 2022 which will happen in person again.
What do you want patients, survivors, caregivers and families touched by pancreatic cancer to know about Mazur Labs?
Our lab is committed to find new therapeutic options for pancreatic cancer patients. Currently we are pursuing different approaches to find a cure or to at least turn pancreatic cancer into a chronic disease.
One major setback with current treatment options is the development of therapy resistance. Therefore, we aim to identify novel therapeutic targets that help overcome resistance to current treatment agents. Another approach in our lab is to develop an innovative immunotherapy that can be combined with current treatment modalities that will hopefully result in tumor regression.