Research Development and Innovation

SLIRP – a novel protein with applications in cancer treatment and diagnosis and disorders of metabolism.

Opportunity

UWA is offering partnership in an early-stage collaborative development and commercialisation opportunity to evaluate the potential of SLIRP as a therapeutic target and diagnostic marker in cancer. With a suitable partner we intend to establish whether SLIRP is:

• a therapeutic target for diseases involving hormones as the proliferative driver (i.e. estrogens in breast cancer, androgens in prostate cancer)
• able to serve as a novel clinical biomarker in cancer
• involved in the regulation of energy/metabolism disorders.

The cancer-related applications have considerable market potential and validated technology should be an attractive in-licensing opportunity for biotech / pharma companies operating in cancer medicine. Whilst preliminary, there is also data showing that SLIRP is closely associated with mitochondria and abundant in energy-rich tissues. Exploring applications in metabolism disorders would also be an attractive research and investment opportunity.

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Summary

Estrogen and other hormones play key roles in triggering the proliferation of cancer cells. Selective Estrogen Receptor Modulators (SERM’s), such as tamoxifen for the treatment of breast cancer, are now standard therapies and recognised to be valuable targets for intervention.

SLIRP has been shown to be an important modulator in the hormone receptor signalling pathways of cancer cells. This activity is via association with a steroid receptor RNA activator (SRA), an established activator of the estrogen receptor (ER), and results in the repression of the ER and consequent loss of estrogen signaling activity.

Additionally, SLIRP has been shown to repress the glucocorticoid receptor (GR), another important pathway that is targeted by cancer therapeutics.

Recent research at WAIMR has confirmed that:

• SLIRP is a novel RNA binding protein that binds to a specific region of SRA.
• SLIRP is expressed in breast, prostate and lung cancer cell lines as well as breast cancer tissue, normal tissues and other hormone-dependent tissues such as ovary and testes.
• SLIRP represses SRA-mediated transactivation of estrogen- and glucocorticoid- responsive reporters.

Furthermore SLIRP is abundant in energy-rich tissues such as muscle, heart and liver and has been shown to be localised in mitochondria; this suggests that SLIRP may participate in controlling energy processes via the mitochondria and that it might prove to be a useful therapeutic target.

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Intellectual Property

‘SRA Binding Protein’ - Provisional Patent Application 2005903903, July 2005 and supplementary information added to 2005907268, Dec 2005. Includes claims to therapeutic, diagnostic and prognostic applications of SLIRP and regions of the protein understood to be functionally important. The patent applications and a draft publication can be accessed under a UWA Confidentiality Agreement.

Research required

Further research is required to establish the distribution of SLIRP in other diseased and normal tissues, to:

• determine if expression levels of SLIRP will serve as a useful clinical prognostic biomarker
•  to investigate whether SLIRP has tumour-suppressor activity; and
• to determine whether SLIRP could have a role in the treatment of cancer using conventional therapies.

In addition, the potential for SLIRP to play a role in regulating mitochondrial function and/or gene expression within energy rich tissues requires further investigation. These areas offer further scope to create new intellectual property.

SLIRP was recently awarded significant NH&MRC grant funding and whilst this will enable the team to extend their knowledge of SLIRP the project could be accelerated through early partnering.

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Commercialisation

This is an early-stage opportunity and requires significant research to validate and develop the preliminary findings. UWA is seeking a partner to assist with these pre-clinical investigations and to collaborate on the commercialisation and intellectual property strategy.

For a partner willing to invest in the technology UWA is prepared to offer an exclusive option or a license to the SLIRP IP. It is envisaged that UWA and the partner would agree on a minimum 18 month research project at UWA, with provisions in the agreement for the partner to secure a long term relationship if desired.

A potential partner wishing to exclusively evaluate the SLIRP IP could do so via a short-term (90 day) option with a modest option fee.

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