Novel therapeutic strategies for pancreatic cancer, gastric cancer, and bile duct cancer:

Pancreatic cancer, gastric cancer, and bile duct cancer (cholangiocarcinoma) are challenging diseases to treat. These cancers are highly resistant to conventional therapies and have very poor prognoses, with a median survival time remaining less than a year. Our laboratory research is focused on understanding the molecular mechanisms of tumor progression and determining novel and more effective therapeutic strategies for these upper gastrointestinal cancers. We have developed and established several highly effective, reproducible, and efficient animal models including subcutaneous, orthotopic, peritoneal dissemination and patient-derived xenografts, to evaluate experimental therapeutics in these cancers, as represented in 50 research article publications in the peer-reviewed journals. Our preclinical research work in pancreatic cancer demonstrated that nab-paclitaxel is a superior chemotherapeutic agent compared with gemcitabine or docetaxel, and the addition of antiangiogenic agents enhanced nab-paclitaxel antitumor response. These research findings played a significant role in the FDA approval of the nab-paclitaxel and gemcitabine combination for the treatment of advanced pancreatic cancer. The clinical and translation impact of our research is evident by several Industry-Sponsored Research Grants and Cancer Research Foundation Grants in recent years. My research objectives are to develop novel and more effective therapeutic strategies and delineate the mechanism(s) of antitumor efficacy of these therapies for improving the clinical outcome of patients with advanced pancreatic, gastric and bile duct cancer.

Selected Publications:

1. Meghan Grojean, Schwarz MA, Schwarz JR, Hassan MS, von Holzen U, Changhua Zhang, Schwarz RE, Awasthi* N. 2020. Targeted dual inhibition of c-Met/VEGFR2 signaling by foretinib improves antitumor effects of nanoparticle paclitaxel in gastric cancer model. J Cell Mol Med 25:4950-4961.
    
2. Awasthi N, Kronenberger D, Stefaniak A, Hassan MS, von Holzen U, Schwarz MA, Schwarz RE. 2019. Dual inhibition of the PI3K and MAPK pathways enhances nab-paclitaxel/gemcitabine chemotherapy response in preclinical models of pancreatic cancer. Cancer Lett 459:41-49.
    
3. Awasthi N, Mikels-Vigdal AJ, Stefanutti E, Schwarz MA, Monahan S, Smith V, Schwarz RE. 2019. Therapeutic efficacy of anti-MMP9 antibody in combination with nab-paclitaxel-based chemotherapy in pre-clinical models of pancreatic cancer. J Cell Mol Med 23:3878-3887.
    
4. Zhou Z, Xia GK, Xiang Z, Liu M, Wei ZW, Yan J, Chen W, Zhu JT, Awasthi N, Sun X, Fung KM, He Y, Li M, Zhang CH. 2019. A C-X-C chemokine receptor type 2-dominated crosstalk between tumor cells and macrophages drives gastric cancer metastasis. Clin Cancer Res 25:3317-3328.
    
5. Awasthi N, Schwarz MA, Zhang C, Schwarz RE. 2018. Augmentation of nab-paclitaxel chemotherapy response by mechanistically diverse antiangiogenic agents in preclinical models of pancreatic cancer. Mol Cancer Ther 17(11):2353-2364.
    
6. Xiang Z, Zhou Z-J, Xia G-K, Zhang X-H, Wei Z-W, Zhu J-T, Yu J, Chen W, He Y, Schwarz RE, Brekken RA, Awasthi N and C-H Zhang. 2017. A positive crosstalk between CXCR4 and CXCR2 promotes gastric cancer metastasis. Oncogene 36:5122-5133.
    
7. Awasthi N, Zhang C, Stefan H, Brekken RA, Schwarz MA, Schwarz RE. 2015. Nintedanib, a triple angiokinase inhibitor, enhances cytotoxic therapy response in pancreatic cancer. Cancer Lett 358:59-66.
    
8. Awasthi N, Zhang C, Schwarz AM, Stefan H, Schwarz MA, Schwarz RE. 2014. Enhancement of nab-paclitaxel antitumor activity through addition of multitargeting antiangiogenic agents in experimental pancreatic cancer. Mol Cancer Ther 13:1032-43.
    
9. Awasthi N, Zhang C, Schwarz AM, Stefan H, Wang C, Williams NS, Schwarz MA, Schwarz RE. 2013. Comparative benefits of nab-paclitaxel over gemcitabine or polysorbate-based docetaxel in experimental pancreatic cancer. Carcinogenesis 34:2361-9.
    
10. Awasthi N, Zhang C, Ruan W, Schwarz MA, Schwarz RE. 2012. BMS-754807, a Small molecule inhibitor of insulin-like growth factor-1 receptor / insulin receptor, enhances gemcitabine response in pancreatic cancer. Mol Cancer Ther 11:2644-53