The multiple roles and therapeutic potential of clusterin in non-small-cell lung cancer: a narrative review

Abstract

Worldwide, lung cancer is the most common form of cancer, with an estimated 2.09 million new cases and 1.76 million of death cause in 2018. It is categorized into two subtypes, small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). Although platinum-based chemotherapy or molecular targeted drugs is recommended for advanced stages of NSCLC patients, however, resistance to drug and chemotherapy are hindrances for patients to fully beneficial from these treatments. Clusterin (CLU), also known as apolipoprotein J, is a versatile chaperone molecule which produced by a wide array of tissues and found in most biologic fluids. There are studies reported high expression of CLU confers resistance to chemotherapy and radiotherapy in different lung cancer cell lines. By silencing CLU using Custirsen (OGX-011), a second-generation antisense oligonucleotide (ASO) that inhibits CLU production, not only could sensitized cells to chemo- and radiotherapy, also could decreased their metastatic potential. We will review here the extensive literature linking CLU to NSCLC, update the current state of research on CLU for better understanding of this unique protein and the development of more effective anti- CLU treatment.

Keywords: Non-small-cell lung cancer (NSCLC); antisense oligonucleotide; chemotherapy; clusterin (CLU); radiotherapy.

Figure 1

Molecular function of clusterin in tumorgenesis.