Patented therapeutic approaches targeting LRP/LR for cancer treatment

ABSTRACT

Introduction: The ubiquitously expressed 37 kDa/67 kDa high-affinity laminin receptor (laminin receptor precursor/laminin receptor, LRP/LR) is a protein found to play several roles within cells. The receptor is located in the nucleus, cytosol and the cell surface. LRP/LR mediates cell proliferation, cell adhesion and cell differentiation. As a result, it is seen to enhance tumor angiogenesis as well as invasion and adhesion, key steps in the metastatic cascade of cancer. Recent findings have shown that LRP/LR is involved in the maintenance of cell viability through apoptotic evasion, allowing for tumor progression. Thus, several patented therapeutic approaches targeting the receptor for the prevention and treatment of cancer have emerged.

Areas covered: The several roles that LRP/LR plays in cancer progression as well as an overview of the current therapeutic patented strategies targeting LRP/LR and cancer to date.

Expert opinion: Small molecule inhibitors, monoclonal antibodies and small interfering RNAs might act used as powerful tools in preventing tumor angiogenesis and metastasis through the induction of apoptosis and telomere erosion in several cancers. This review offers an overview of the roles played by LRP/LR in cancer progression, while providing novel patented approaches targeting the receptor as potential therapeutic routes for the treatment of cancer as well as various other diseases.

KEYWORDS:

• Angiogenesis
• antibody
• apoptosis
• cancer
• laminin receptor precursor/laminin receptor
• metastasis
• nanoparticles
• small interfering RNA
• telomerase
• therapy

Article highlights

• Synthetic and natural small molecule inhibitors have been shown to have a positive effect on metastasis in several cancer cell types.

• Monoclonal anti-LRP/LR specific antibody, IgG1-iS18, has been shown to decrease adhesion and invasion in several cancer types.

• Small interfering RNAs targeting LRP/LR are found to decrease cell survival through the induction of apoptosis.

• Potential avenues of targeting LRP/LR include investigating the formation of the 67 kDa LR form, as well as its relationship with proteins parkin, telomerase and RNF8.

This box summarizes key points contained in the article.

Author contributions

L Vania: leading author on review, wrote the majority and contributed to several of the sections of the review. She was involved in conceptualizing the figures and edited the review. G Morris: wrote the sections ‘Structure and Function of LRP/LR’, ‘Oncofoetal antigen/immature laminin receptor protein’ ‘Dendritic cell therapies’, and some sections for ‘SMIs targeting LRP’ and ‘Potential avenues for targeting LRP/LR in cancer’. He constructed the figures. TC Otgaar: contributed to the ‘LRP/LR and Telomerase’ section and edited the review. MJ Bignoux: contributed to the ‘LRP and Telomerase’ section. M Bernert: edited the review. J Burns: wrote the ‘LRP and Parkin’ section. A Gabathuse: provided a list of existing patents. E Singh: wrote the ‘Epidemiology’ section. E Ferreira: edited the review. SFT Weiss: wrote with J Burns the LRP and Parkin section. He wrote the ‘Conclusion’ and ‘Expert Opinion’ sections, and edited the review. All authors finally approved the version to be published; all authors agree to be accountable for all aspects of the work.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work is based upon research supported by the National Research Foundation (NRF), the Republic of South Africa (RSA), Grant Numbers 105832, 99061 and 118851. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s), and therefore, the National Research Foundation does not accept any liability in this regard thereto. Financial support was received from the South African Medical Research Council (SAMRC) under the Wits Common Epithelial Cancer Research Centre (CECRC) grant. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s), and therefore, the SAMRC does not accept any liability in this regard thereto. Financial support was further received from the Cancer Association of South Africa (CANSA). Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s), and therefore, CANSA does not accept any liability in this regard thereto.