Stroma-Targeting Therapy in Pancreatic Cancer: One Coin With Two Sides?

Pancreatic ductal adenocarcinoma (PDAC) is a malignancy with one of the worst prognoses worldwide and has an overall 5-year survival rate of only 9%. Although chemotherapy is the recommended treatment for patients with advanced PDAC, its efficacy is not satisfactory. The dense dysplastic stroma of PDAC is a major obstacle to the delivery of chemotherapy drugs and plays an important role in the progression of PDAC. Therefore, stroma-targeting therapy is considered a potential treatment strategy to improve the efficacy of chemotherapy and patient survival. While several preclinical studies have shown encouraging results, the anti-tumor potential of the PDAC stroma has also been revealed, and the extreme depletion might promote tumor progression and undermine patient survival. Therefore, achieving a balance between stromal abundance and depletion might be the further of stroma-targeting therapy. This review summarized the current progress of stroma-targeting therapy in PDAC and discussed the double-edged sword of its therapeutic effects.