Mazur Laboratory
Pawel K. Mazur, Ph.D.
Assistant Professor
Areas of Research
- Pancreatic Cancer
- Lung Cancer
- Immunotherapy
- Targeted Therapy
- Drug Development
- Molecular Biology
Welcome to the Mazur Laboratory at MD Anderson Cancer Center. Our work focuses on the identification of novel drug targets that can efficiently treat lung and pancreatic cancers, the two most deadly human malignancies. Our goal is to spearhead the development of novel targeted drugs and immunotherapies that enable precision medicine clinical trials for cancer patients.
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Pancreatic cancer is one of the deadliest and most aggressive forms of cancer. There is an urgent need to develop new drugs and immunotherapeutic combinations to treat this disease and overcome drug resistance.
- Over 48,000 Americans will be diagnosed this year and over 95% will die from this deadly disease.
- More than 50% of patients die within the first 6 months of diagnosis
- Pancreatic cancer is one of the few cancers for which survival has not substantially improved over the past 25 years
- Pancreatic cancer is projected to surpass breast, prostate, and colorectal cancers to become the 2nd leading cause of cancer-related death by 2020
Lung cancer is the leading cause of cancer-related death in the US and worldwide. A major unmet need for lung cancer treatment is the identification of new therapeutic targets, which requires elucidating the critical genes and molecular pathways driving this disease.
- This year, 116,470 men and 109,690 women will be newly diagnosed with lung cancer in the US. Over 165,000 of them will die from this deadly disease this year. That’s about 452 deaths a day.
- Lung cancer accounts for over 1 million deaths each year worldwide – that is more deaths than colon, breast and prostate cancer combined.
- The chance that a man will develop lung cancer in his lifetime is about 1 in 13 and for a woman, 1 in 16
- Lung cancer remains one of the most lethal of malignancies in part due to the development of drug resistance and rare response to immunotherapy
Our work is dedicated to translating cancer discovery into cancer cures.
Our aim is to define upfront polytherapy approaches based upon deep systematic interrogation of the aberrant molecular pathways operating in lung and pancreatic cancer to combat or eliminate targeted and immunotherapy resistance and transform the two most deadly human cancers from lethal disease into a chronic or curable condition.
Our approach is to develop novel promising immunotherapy approaches using T lymphocytes (more commonly known as T cells) engineered with chimeric antigen receptors (CARs). Once the T cell has been engineered to become a CAR T cell, it acts as a "living drug" that exhibits a new specificity to kill cancer cells.
Our goal is to build a comprehensive disease modeling platform to study novel signaling networks and generate innovative immunotherapeutics using animal models that frightfully represent human disease to better understand mechanisms of cancer progression and drug resistance. Our ultimate goal is to guide clinical drug development for precision medicine clinical trials.
Spotlight on Our Research
A novel combination therapy for pancreatic cancer
NATURE MEDICINE, 2015
Major finding:
Dual inhibition of BET proteins and HDACs synergistically suppresses PDAC development and maintenance.
Mechanism:
JQ1 inhibits MYC and inflammatory cytokines, and synergizes with SAHA to activate p57 and induce death.
Impact:
PDAC is sensitive to epigenetic-based therapies, which may be quickly implemented for patient use or clinical drug development.
A novel regulatory mechanism can be manipulated to treat pancreatic cancer
NATURE, 2014
SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer
Major finding:
SMYD3-mediated MAP3K2methylation activates RAS signaling and drives carcinogenesis in vivo.
Mechanism:
Methylation of MAP3K2 by SMYD3 disrupts binding to PP2A and activates MEK1/2 signaling.
Impact:
Those results reveal an unexpected role for lysine methylation in a kinase signalling pathway and establish SMYD3 as a potential therapeutic target for clinical drug development.
Scaffold blockade inhibits pancreatic cancer
NATURE MEDICINE, 2013
IQGAP1 Scaffold-Kinase Interaction Blockade Selectively Targets RAS-MAP Kinase Driven Tumors
Major finding:
Disruption of IQGAP1 scaffold function inhibits oncogenic ERK signaling without toxicity.
Mechanism:
An IQGAP1 peptide reduces RAS/RAF–driven tumor growth and bypasses vemurafenib resistance.
Impact:
Blockade of scaffold-kinase interactions can complement direct kinase inhibition for pancreatic cancer treatment and clinical drug development.
Critical regulator of tumorigenesis in the pancreas and lung uncovered
GENES & DEVELOPMENT, 2016
Coordination of stress signals by the lysine methyltransferase SMYD2 promotes pancreatic cancer
Major finding:
Loss of SMYD2 function reduces the growth of various tumor cell populations while its overexpression is pro-tumorigenic.
Mechanism:
SMYD2 methylation of MK3 stress kinase promotes the proliferation and the survival of pancreas and lung cancer cells.
Impact:
Inhibition of SMYD2 cooperates with standard chemotherapy to treat pancreatic cancer cells and reduces growth of patient derived tumors.