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ELESCLOMOL

Program Overview |  Presentations & Publications |  References

Program Overview

About Elesclomol

Elesclomol is a first-in-class, investigational drug candidate that triggers apoptosis (programmed cell death) in cancer cells by disrupting cancer cell energy production and metabolism.

Preclinical studies have shown that elesclomol acquires copper ions, in the form of Cu(II), from serum, and, once inside a cancer cell, enables the reduction reaction Cu(II) to Cu(I). This redox reaction disrupts mitochondrial respiration in cancer cells and elevates the level of reactive oxygen species (ROS) beyond sustainable levels. This increase in ROS overwhelms the cancer cells and ultimately triggers the mitochondrial apoptosis pathway.1,2 This mechanism of action represents a novel way of selectively targeting and killing cancer cells.

The induction of apoptosis by elesclomol has been observed in a wide variety of cancer cell types. The anti-cancer activity of elesclomol has also been shown to require energy metabolism driven primarily through the mitochondria. This occurs under normoxic (normal oxygen) conditions. Under hypoxic conditions, often associated with elevated LDH levels, energy production shifts to glycolysis in the cytoplasm and elesclomol anti-cancer activity is diminished.3 These observations are consistent with findings in a Phase 3 metastatic melanoma study, where elesclomol activity was observed in subjects with normal baseline LDH levels, but not in subjects with elevated LDH levels.4

Plans for future clinical trials with elesclomol will be announced later in 2010.

1 Kirshner JR, He S, Balasubramanyam V, Kepros J, Yang CY, Zhang M, Du Z, Barsoum J, Bertin J. Elesclomol induces cancer cell apoptosis through oxidative stress. Molecular Cancer Therapy 2008 Aug; 7(8):2319-27.

2 Nagai M, Vho N, Kostik E, He S, Kepros J, Ogawa LS, Inoue T, Blackman RK, Wada Y, Barsoum J. The oxidative stress inducer elesclomol requires copper chelation for its anticancer activity. Molecular Cancer Therapeutics 2009; 8 (12, suppl 1): Abstract C11. Poster presented at 2009 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, Boston, MA

3 Nagai M, Blackman RK, Rao PE, Wada Y, Koya K. Anticancer activity of elesclomol correlates with low LDH levels and active mitochondrial respiration. Presented at: American Association for Cancer Research Annual Meeting, April 2010, Washington DC

4 Hauschild A, Eggermont AM, Jacobson E, O’Day SJ. Phase III, Randomized, double-blind study of elesclomol and paclitaxel versus paclitaxel alone in Stage IV Metastatic Melanoma (MM). J Clin Oncol 2009; 27 (18s); abstract LBA9012. Presented at American Society of Clinical Oncology Annual Meeting, 2009.

Elesclomol Presentations

Meeting/Date Title Link

ASCO Annual Meeting 2010
June 6, 2010 - Chicago, IL

Phase III, randomized, double-blind study of elesclomol and paclitaxel versus paclitaxel alone in stage IV metastatic melanoma (MM): 1-year OS update. Poster

Abstract

101st AACR Annual Meeting
April 20, 2010 - Washington, DC

Anticancer activity of elesclomol correlates with low LDH levels and active mitochondrial respiration Poster

Abstract

101st AACR Annual Meeting
April 20, 2010 - Washington, DC

Targeting ROS to kill cisplatin-resistant cells Poster

Abstract

ASH 2009
Annual Meeting of the American Society of Hematology
December 6, 2009 - New Orleans, LA

Antileukemic Effects of the Novel Agent Elesclomol. Poster

Abstract
AACR-NCI-EORTC
Molecular Targets and Cancer Therapeutics
November 18, 2009 - Boston, MA
The oxidative stress inducer elesclomol requires copper chelation for its anticancer activity. Poster

Abstract
Perspectives in Melanoma XIII
October 10, 2009 - Baltimore, MD
SYMMETRYSM Clinical Trial Update Presentation
ASCO Annual Meeting 2009
May 30, 2009 - Orlando, FL
Phase 3, randomized, double-blind study of elesclomol and paclitaxel versus paclitaxel alone in Stage IV metastatic melanoma. Abstract
100th AACR Annual Meeting
April 21, 2009 - Denver, CO
Elesclomol and chemotherapy agents synergistically induce apoptosis in breast cancer cells. Abstract

Elesclomol Publications

Publication/Date Title Link
Journal of Clinical Oncology
November 2009; 27(32): 5452-5458.
A Phase II, Randomized, Controlled, Double-Blinded Trial of Weekly Elesclomol Plus Paclitaxel Versus Paclitaxel Alone for Stage IV Metastatic Melanoma. Abstract
Breast Cancer Research Treatment
2009 July 16. [Epub ahead of print]
Elesclomol, counteracted by Akt survival signaling, enhances the apoptotic effect of chemotherapy drugs in breast cancer cells. Publication
Molecular Cancer Therapeutics
August 2008; 7(8): 2319-2327.
Elesclomol induces cancer cell apoptosis through oxidative stress. Publication

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References

Oxidative Stress and Cancer
  • Fruehauf, J.P., Meyskens, FL: Reactive Oxygen Species: A Breath of Life or Death? Clinical Cancer Research; 13(3) February 2007, 789-794.
  • Fruehauf, J.P., Trapp, V: Reactive oxygen species: an Achilles' heel of melanoma? Expert Review of Anticancer Therapy. 8(11) November 2008, 1751-1757.
  • Gastpar, R., Gehrmann, M., et.al.: Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res, 2005; 65 (12).
  • Massa, C., et.al.: Enhanced efficacy of tumor cell vaccines transfected with secretable hsp70. Cancer Res, 2004; 64:1502-1508.
  • Noessner, E., et.al.: Tumor-derived heat shock protein 70 peptide complexes are cross-presented by human dendritic cells. J of Immunology, 2002; 169:5424-5432.
  • O'Day, S., et.al.: A Phase II, Randomized, Controlled, Double-Blinded Trial of Weekly Elesclomol Plus Paclitaxel Versus Paclitaxel Alone for Stage IV Metastatic Melanoma. J Clin Oncol. 2009 Oct 13. [Epub ahead of print].
  • Pelicano, H., et al: ROS stress in cancer cells and therapeutic implications, Drug Resistance Updates 7 (2004) 97-110.
  • Ramanathan, B., et al: Resistance to Paclitaxel is Proportional to Cellular Total Antioxidant Capacity, Cancer Research 65: (18), September 2005, 8455-8460.
  • Schmitt, E., et.al.: Intracellular and extracellular functions of heat shock proteins: repercussions in cancer therapy. J of Leukocyte Biology, 2007; Vol 81 (published as DOI 10.1189/jlb.0306167, Aug 2006).
  • Schumacker, P.T.: Reactive oxygen species in cancer cells: Live by the sword, die by the sword, Cancer Cell, September 2006, 175-176.

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