Preclinical evaluation of an unconventional ruthenium-gold-based chemotherapeutic: RANCE-1, in clear cell renal cell carcinoma.

Abstract

BACKGROUND:

There are few effective treatments for patients with advanced clear cell renal cell carcinoma (CCRCC). Recent findings indicate that ruthenium-gold containing compounds exhibit significant antitumor efficacy against CCRCC in vitro affecting cell viability as well as angiogenesis and markers driving those 2 phenomena. However, no in vivo preclinical evaluation of this class of compounds has been reported.

METHODS:

Following the dose-finding pharmacokinetic determination, NOD.CB17-Prkdc SCID/J mice bearing xenograft CCRCC Caki-1 tumors were treated in an intervention trial for 21 days at 10 mg/kg/72h of RANCE-1. At the end of the trial, tumor samples were analyzed for histopathological and changes in protein expression levels were assessed.

RESULTS:

After 21 days of treatment there was no significant change in tumor size in the RANCE-1-treated mice as compared to the starting size (+3.87%) (P = 0.082) while the vehicle treated mice exhibited a significant tumor size increase (+138%) (P < 0.01). There were no signs of pathological complications as a result of treatment. Significant reduction in the expression of VEGF, PDGF, FGF, EGFR, and HGRF, all key to the proliferation of tumor cells and stromal cells serving protumorigenic purposes was observed.

CONCLUSIONS:

The tumor growth inhibition displayed and favorable pathology profile of RANCE-1 makes it a promising candidate for further evaluation toward clinical use for the treatment of advanced CCRCC.

• Authors: Benelita T Elie, Karen Hubbard, Yuriy Pechenyy, Buddhadev Layek, Swayam Prabha, Maria Contel
• Journal: Cancer medicine (Cancer Med) Vol. 8 Issue 9 Pg. 4304-4314 (08 2019) ISSN: 2045-7634 [Electronic] United States
• PMID: 31192543 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Chemical References

• Angiogenic Proteins
• Organometallic Compounds
• Gold
• Ruthenium

Topics

• Angiogenic Proteins (metabolism)
• Animals
• Carcinoma, Renal Cell (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Gold (chemistry)
• Humans
• Kidney Neoplasms (drug therapy, metabolism, pathology)
• Male
• Mice
• Organometallic Compounds (administration & dosage, chemical synthesis, chemistry, pharmacokinetics)
• Ruthenium (chemistry)
• Treatment Outcome
• Xenograft Model Antitumor Assays