Purpose Scoping reviews address the nature of the literature per se rather than inferring evidence-based treatment guidelines. Scoping reviews of the published literature are intended to describe the aggregated nature of the evidence surrounding some agent or intervention, in contrast to systematic reviews that seek when possible to guide clinical practice. We conducted a scoping review to identify reports of potential clinical utility of off-label topical analgesics and adjuvants when FDA-approved treatments have proven inadequate. Methods We performed a comprehensive search of three databases (PubMed, Web of Science and Embase) for articles dating from 1947 to the present. Mindful that FDA-approved and WHO-recommended analgesic medications often prove inadequate for individual patients in extremis with palliative, hospice or cancer pain, we used broad, structured inclusion criteria to retrieve articles. Results We retrieved 12,100 articles; after screening, we had 39 reports addressing 19 different topical agents out of the 32 chemical entities. Our scoping review disclosed evidence about agents that might not have met inclusion criteria for clinical practice guidelines. Discussion Although generally considered lower quality evidence, case reports or series present suggestions for diverse topical medications to manage pain in challenging circumstances when high-quality evidence for agents and routes of administration is lacking. Conclusion Patients with the greatest need for evidence to identify and guide lesser-used agents during aggressive pain management are the most difficult to enroll and follow in standardized, controlled and/or blinded clinical trials. This scoping review identifies medications, dosages, and routes of topical agents reported to be effective in these often-challenging circumstances. Until larger and higher quality studies are completed, we must rely on the best available evidence even if of lower quality.

Triple negative breast cancer (TNBC) is one of the most aggressive types of breast cancer accounting for 12% of breast cancer cases. It is characterized by the lack of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER‐2), which limits treatment options and enhances its ability to metastasize with the risk of recurrence. Patients with TNBC are not responsive to conventional therapies. Capsaicin (CAP) is the most abundant capsaicinoid produced in chili pepper fruits and has been utilized for its analgesic and anti‐inflammatory effects. While several studies have demonstrated that capsaicin has anti‐carcinogenic properties in various types of human cancers, the underlying molecular mechanisms remain to be explored. The aim of this study was to investigate the effects of capsaicin in human TNBC, utilizing a BT‐20 cell model. Capsaicin demonstrated concentration‐ and time‐dependent in the viability of BT‐20 cells, as determined by the MTS assay. Capsaicin caused significant increases in cytochrome C release, caspase 3/7 activity and expression of cleaved poly‐(ADP‐ribose) polymerase (PARP), all of which are markers of apoptotic activation. These effects were accompanied by down‐regulation of cyclin D1 production, an indicator of cell cycle arrest at the G0/G1 phase. Further analyses of signaling mechanisms revealed that capsaicin significantly inhibited EGFR phosphorylation and the phosphorylation of its downstream signaling proteins AKT and MAPK, which may provide some explanation for its mechanism of action in TNBC. In conclusion, capsaicin has demonstrated inhibitory effects on cell growth and cell cycle progression on TNBC cells by enhancing apoptosis. Our data demonstrated a novel mechanism for capsaicin, modulating EGFR signaling by AKT/MAPK pathways in BT‐20 cells. These results provide useful information relevant to the development of a potential new therapy to treat TNBC with capsaicin.Support or Funding InformationThis work was funded by the College of Medicine, King Saud bin Abdulaziz University for Health Sciences (KSAU‐HS), Jeddah, Saudi Arabia.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.