Meeting the needs of breast cancer: A nucleolin’s perspective

Abstract

A major challenge in the management of breast cancer disease has been the development of metastases. Finding new molecular targets and the design of targeted therapeutic approaches to improve the overall survival and quality of life of these patients is, therefore, of great importance. Nucleolin, which is overexpressed in cancer cells and tumor-associated blood vessels, have been implicated in various processes supporting tumorigenesis and angiogenesis. Additionally, its overexpression has been demonstrated in a variety of human neoplasias as an unfavorable prognostic factor, associated with a high risk of relapse and low overall survival. Hence, nucleolin has emerged as a relevant target for therapeutic intervention in cancer malignancy, including breast cancer. This review focus on the contribution of nucleolin for cancer disease and on the development of therapeutic strategies targeting this protein. In this respect, it also provides a critical analysis about the potential and pitfalls of nanomedicine for cancer therapy.

Druggable Nucleolin Identifies Breast Tumours Associated with Poor Prognosis That Exhibit Different Biological Processes

“…A second study reported that NCL expression level was over-expressed in mammary tumours compared to normal tissues using both immunohistochemistry (IHC) in a panel of eight normal/tumour pairs and NanoString-quantified mRNA levels in 57 normal vs. 183 triple-negative breast cancer [ 15 ]. A recent review reported similar observations on small series [ 6 ]. These data are concordant with our observation that tumours of the high NCL -expressing group expressed more NCL mRNA levels than healthy mammary tissues.…”

“…Overall, our data open up interesting opportunities in clinics. First, several promising anti-NCL drugs have been developed to fight liquid and solid cancers that are currently evaluated in clinical trials phase II [ 2 , 5 , 6 , 7 , 8 , 9 , 10 ]. Compared to intermediate and low NCL -expressing tumours, tumours expressing high NCL are the most prone to respond to anti-NCL drugs.…”

“…Several drugs targeting NCL have been developed that specifically induced cell death of tumour cells [ 2 , 5 , 6 ]. Among them, two anti-NCL have been evaluated in clinical trials.…”

“…In contrast, the NCL-targeted DNA aptamer AS1411 has shown only limited efficacy in a phase II clinical trial on unselected patients with advanced stage of renal cell carcinoma: only one patient out of the 35 enrolled ones showed dramatic reduction of tumour burden [ 7 ]. Interestingly, most of the anti-NCL therapies have been evaluated in vitro and in vivo using triple-negative breast cancer models and showed strong cytotoxic effects, making NCL a powerful candidate for future evaluation of anti-NCL in breast cancer [ 6 ]. Indeed, the antibody 4LB5 inhibiting NCL activity decreased MDA-MB-231 cell viability, clonogenicity, and tumour growth in xenografts while inducing apoptosis [ 8 ].…”

“…At present, the role of NCL in cancer is supported only by few studies using human samples that showed the association of NCL expression with poor overall survival both in solid and liquid cancers [ 6 , 11 , 12 , 13 ]. In breast cancer, only two studies investigated NCL expression.…”