Senior Research Professor at Indiana University School of Medicine - South Bend
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States, and is expected to become the second-leading cause of cancer death by 2030. Gemcitabine (Gem), the standard of care agent, has modest clinical benefit. Gemcitabine combination with nab-paclitaxel (NPT) has shown improved clinical activity in advanced PDAC. The low survival rate of PDAC patients warrants further evaluation of other anticancer drugs that block the potential pathways of PDAC progression.
Our research work is focused on evaluating combination therapy benefits in PDAC. We demonstrated that NPT is a superior chemotherapeutic agent compared with gemcitabine or docetaxel (1). Furthermore, we showed the enhancement in NPT antitumor activity by addition of antiangiogenic agents, bevacizumab and sunitinib (2). These research findings played a significant role in recent FDA approval of the nab-paclitaxel plus gemcitabine combination for the treatment of advanced PDAC. Recently, we showed that nintedanib, a triple angiokinase inhibitor, enhances cytotoxic therapy response in PDAC (3). We are currently evaluating the recently approved chemotherapy regimen NPT plus Gem, in combination with potential targeted agents involved in PDAC progression such as MAPK and PI3K inhibitor, TGFb inhibitor, MMP-9 inhibitor and JAK1/2 inhibitor. These studies will provide a better understanding of molecular mechanisms of PDAC progression and open realistic avenues to double patient survival. Our lab is also focused on finding a novel and more effective treatment for gastric adenocarcinoma (GAC) that is the fourth most common cancer worldwide. The prognosis of metastatic GAC patients is generally poor with a median overall survival of 3-5 months. Systemic chemotherapy is commonly recommended as a fundamental treatment for metastatic GAC that usually leads to a median survival of 8 to 10 months. Therefore, novel and effective therapeutic strategies are urgently required to improve outcome for patients with metastatic GAC. In our lab, we established human GAC xenograft models in mice to study effects of anticancer drugs on animal survival, tumor growth and metastasis. We demonstrated that NPT has superior antitumor activity in GAC (4). Angiogenesis is a well-established target for the treatment of GAC. We are currently evaluating enhancement in cytotoxic chemotherapy agents (5-FU, docetaxel, cisplatin, irinotecan, epirubicin, NPT) response by addition of mechanistically different antiangiogenic agents such as bevacizumab, ramucirumab (or DC101), cabozantinib, regorafenib and nintedanib.
1. Awasthi N, et al. (2013). Carcinogenesis 34:2361-69.
2. Awasthi N, et al. (2014). Mol Cancer Thera 13:1032-43.
3. Awasthi N, et al. (2015). Cancer Lett 358:59-66.
4. Zhang C, Awasthi N, et al. (2013). PLoS ONE 8(2):e58037.