Drug delivery approaches for HuR-targeted therapy for lung cancer

Lung cancer (LC) is often diagnosed at an advanced stage and conventional treatments for disease man-agement have limitations associated with them. Novel therapeutic targets are thus avidly sought for the effective management of LC. RNA binding proteins (RBPs) have been convincingly established as key play -ers in tumorigenesis, and their dysregulation is linked to multiple cancers, including LC. In this context, we review the role of Human antigen R (HuR), an RBP that is overexpressed in LC, and further associated with various aspects of LC tumor growth and response to therapy. Herein, we describe the role of HuR in LC progression and outline the evidences supporting various pharmacologic and biologic approaches for inhibiting HuR expression and function. These approaches, including use of small molecule inhibitors, siRNAs and shRNAs, have demonstrated favorable results in reducing tumor cell growth, invasion and migration, angiogenesis and metastasis. Hence, HuR has significant potential as a key therapeutic target in LC. Use of siRNA-based approaches, however, have certain limitations that prevent their maximal exploitation as cancer therapies. To address this, in the conclusion of this review, we provide a list of nanomedicine-based HuR targeting approaches currently being employed for siRNA and shRNA delivery, and provide a rationale for the immense potential therapeutic benefits offered by nanocarrier-based HuR targeting and its promise for treating patients with LC.(c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

Lung cancer is often diagnosed at an advanced stage with limited treatment options. RNA binding proteins, particularly Human antigen R (HuR), have been identified as key players in tumorigenesis, including lung cancer. This review explores the role of HuR in lung cancer progression and highlights various approaches, such as small molecule inhibitors, siRNAs, and shRNAs, for inhibiting HuR expression and function. These approaches have shown promising results in reducing tumor growth, invasion, migration, angiogenesis, and metastasis. Nanomedicine-based HuR targeting approaches using siRNA and shRNA delivery hold immense potential for enhancing cancer therapies in lung cancer patients.