Faculty Bibliography

Purpose of Review: Stent design continues to evolve with newer generation of stents aimed at improving clinical outcomes. This review compares different generations of stents with a focus on biodegradable polymers and stents and their potential benefits. Recent Findings: Drug-eluting stents (DES) reduce stent thrombosis when compared with bare-metal stents (BMS). However, they are associated with impaired vascular healing/endothelialization and excess very long-term events (beyond 1 year). Much of these events (beyond 1 year) have been attributed to continued inflammation due to the polymer. Biodegradable-polymer drug-eluting stents (BP DES) were designed to overcome this polymer related limitation of first-generation DP DES by combining the benefits of reduced in-stent restenosis seen with DES and the benefits of reduced very-late stent thrombosis and myocardial infarction due to absence of polymer with bare-metal stents (BMS). Earlier generation of BP DES showed superiority over first-generation DP DES but at best non-inferior to second-generation DP DES for clinical outcomes; however, the newer-generation BP DES with ultrathin struts show promise in further reducing clinical outcomes when compared with second-generation DP DES. Whether this is due to the biodegradable polymer or the ultrathin struts continues to be debated. Summary: Biodegradable polymer stents in conjunction with ultrathin struts have shown promise as the next generation of DES; however, additional studies and long-term follow-up are needed to confirm these effects.

Targeted therapies require cellular protein expression that meets specific requirements that will maximize effectiveness, minimize off-target toxicities, and provide an opportunity for a therapeutic effect. The receptor tyrosine kinase-like orphan receptors (ROR) are possible targets for therapy that may meet such requirements. RORs are transmembrane proteins that are part of the receptor tyrosine kinase (RTK) family. The RORs have been shown to play a role in tumor-like behavior, such as cell migration and cell invasiveness and are normally not expressed in normal adult tissue. As part of the large effort in target discovery, ROR proteins have recently been found to be expressed in human cancers. Their unique expression profiles may provide a novel class of therapeutic targets for small molecules against the kinase or for antibody-based therapies against these receptors. Being restricted on tumor cells and not on most normal tissues, RORs are excellent targets for the treatment of minimal residual disease, the final hurdle in the curative approach to many cancers, including solid tumors such as neuroblastoma. In this review, we summarize the biology of RORs as they relate to human cancer, and highlight the therapeutic approaches directed toward them.