Locoregional drug delivery for cancer therapy: Preclinical progress and clinical translation

Abstract

Systemic drug delivery is the current clinically preferred route for cancer therapy. However, challenges associated with tumor localization and off-tumor toxic effects limit the clinical effectiveness of this route. Locoregional drug delivery is an emerging viable alternative to systemic therapies. With the improvement in real-time imaging technologies and tools for direct access to tumor lesions, the clinical applicability of locoregional drug delivery is becoming more prominent. Theoretically, locoregional treatments can bypass challenges faced by systemic drug delivery. Preclinically, locoregional delivery of drugs has demonstrated enhanced therapeutic efficacy with limited off-target effects while still yielding an abscopal effect. Clinically, an array of locoregional strategies is under investigation for the delivery of drugs ranging in target and size. Locoregional tumor treatment strategies can be classified into two main categories: 1) direct drug infusion via injection or implanted port and 2) extended drug elution via injected or implanted depot. The number of studies investigating locoregional drug delivery strategies for cancer treatment is rising exponentially, in both preclinical and clinical settings, with some approaches approved for clinical use. Here, we highlight key preclinical advances and the clinical relevance of such locoregional delivery strategies in the treatment of cancer. Furthermore, we critically analyze 949 clinical trials involving locoregional drug delivery and discuss emerging trends.

Keywords: Abscopal effect; Cancer therapy; Depot; Drug delivery systems; Implantable port; Injectable hydrogel; Intratumoral; Local; Microneedles; Ommaya; Scaffold; TACE; Wafer.