Novel therapy for a broad spectrum of tumours: targeting minor class splicing

Novel therapy for a broad spectrum of tumours: targeting minor class splicing

The opportunity

  • Genetic disruption of minor class splicing (MCS) inhibits the growth of multiple cancers.
  • Identifying novel inhibitors of minor class splicing.
  • Approach of phenotypic and targeted HTS.

Pancreatic, colorectal and lung adenocarcinomas are difficult-to-treat cancers with abysmal five-year survival rates. Together they represent a major unmet therapeutic need.

These tumours frequently carry mutations in the KRAS gene causing unrestrained activation of the MAPK pathway. Most genes encoding components of the RAS/MAPK pathway require efficient minor class splicing for their correct expression.

Scientific figure

The technology

Researchers at the Walter and Eliza Hall Institute have found that targeting minor class splicing genetically can arrests tumour growth, while healthy cells remain unaffected.

Two distinct/complementary screening approaches are being pursued to identify small molecules that interfere with the minor class splicing machinery:

1) Phenotypic screen

  • Completed: screened >260,000 compounds against a cell-based splicing reporter assay
  • Ongoing: hit validation stage

2) Targeted screen

  • Planned: alpha screen to target interactions between key components of the minor class splicing machinery

Opportunities for partnership

This opportunity is to develop a drug that helps patients with hard-to-treat tumours, including mutant KRAS-driven lung, liver, colorectal and pancreatic adenocarcinomas.

We have:

  • Preclinical models and a phenotypic screen at hit validation stage.

We are seeking a partner to:

  • Progress target ID of phenotypic screen, targeted screen, medicinal chemistry and preclinical validation.

Scientific team

Associate Professor Joan Heath, Laboratory head, Epigenetics and Development division


Dr Anne-Laure Puaux, Head, Biotechnology and Commercialisation

Phone: +61 3 9345 2175