Metastasis, recurrence and drug resistance are major problems in cancer treatment. Metastasis is responsible for the majority of colorectal cancer mortality, yet the underlying mechanisms are largely unknown. Colorectal cancer has a high metastatic relapse rate, which is thought to be caused by the activation of dormant tumor cells. However, very little is known of the establishment, maintenance and activation of tumor dormancy. 5-FU-base chemotherapy has been the standard care for patients with metastatic colorectal cancer. While improvements in survival have been seen with 5-FU based chemotherapy combinations and biologic agents over the past 20 years, less than 20% of patients diagnosed with metastatic colorectal cancer survive 5 years beyond diagnosis mainly due to intrinsic or acquired resistance to drug treatment. Therefore, there is an urgent need to identify new targets and develop effective therapies to treat metastatic disease and prevent recurrence.
Research in Dr. Wang’s laboratory includes basic and translational research projects, aiming to 1) understand the molecular mechanisms of colorectal cancer metastasis, recurrence, tumor dormancy and drug resistance, 2) identify and validate novel therapeutic targets using cell culture, organoids, mouse models and patient-derived xenografts (PDXs) and 3) develop small molecule inhibitors and test their efficacy in vitro and in vivo. The main goal is to develop novel and effective therapies that can be taken to the clinical trials.
Recently, checkpoint blockade immunotherapy has shown promising results in a variety of cancers including colorectal cancer. As existing immune checkpoint therapies are not universally effective and may be limited by toxicities, discovery of other immunotherapeutic targets and combination strategies is a priority. Dr. Wang’s laboratory has recently developed several projects aiming to identify new therapeutic avenues and facilitate development of novel strategies to prevent cancer immune evasion and increase therapeutic efficacy of immunotherapy.
Research projects include:
- Investigate LGR5 function and its crosstalk with TGFβ signaling in colorectal cancer development and progression.
- Determine whether targeting GRM3-mediated glutamatergic signaling with small molecule inhibitors would be an effective approach to treat metastatic colorectal cancer patients and overcome drug resistance.
- Identify PDK4 substrates and characterize their function in drug resistance and metastasis of colorectal cancer. Determine whether targeting PDK4-mediated signaling with small molecule inhibitors would improve 5-FU efficacy in treating colorectal cancer.
- Characterize tumor dormancy in vitro and in vivo.
- Identify new therapeutic targets involved in cancer immune invasion and determine whether targeting them would increase therapeutic efficacy of immunotherapy.
- Investigate the role of microRNAs in cancer metastasis, tumor dormancy and drug resistance as well as their regulation by different signaling pathways.
- Investigate the role of cancer stem cells (or tumor initiating cells) in cancer metastasis, tumor dormancy and drug resistance.
- Investigate the interaction between microenvironment and tumor cells and its effect on colorectal cancer development, progression and treatment.
Office Location896 Biomedical Research Tower
460 W 12th Ave
Columbus, OH 43210