Novel Target and Therapeutics for Dormant Cancer Cells
Background and Opportunity
Scientists at the ICT have discovered a novel pro-survival protein called TDIF in dormant cancers cells. Dormancy specific modification to TDIF is critical for the viability of dormant cancer cells. When TDIF blockers inhibit this modification in dormant cancer cells it leads to a high accumulation of DNA damage which leads to dormant cancer cell death, preventing their awakening. We have developed AI platform that can identify compounds to block this target. The team used AI methods to identify a series of small molecules that can inhibit this protein modification and demonstrated in vitro efficacy and selectivity in dormant cancer cell models. No effect on normal proliferating cells.
The Problem
Cancer cell dormancy refers to an adaptive response of a cancer cell, after it detaches from the primary tumor and disseminates throughout the body. These disseminated tumor cells (DTCs) enter a state of dormancy or “hibernation”. In this dormant state, DTCs spend most of their time not dividing. DTCs survive like this via the activation of an adaptive survival pathway that facilitates cellular crosstalk between DTCs and host cells in the surrounding microenvironment. DTCs live in the bones, lungs and other hospitable tissues of patients. Eventually, these dormant DTCs “awaken”.
Despite recent advances in cancer treatment, cancer recurrence still poses a major challenge, often involving more aggressive, metastatic disease which remains incurable in the majority of cases. Dormant cancer cells are associated with recurrence, metastasis, and poor clinical outcome, these cells play a crucial role in disease relapse. Dormant cells are by definition in a state of reversible arrested growth, thereby making them unresponsive to the majority of conventional therapies that target actively cycling cell. Currently no specific treatments are available for killing dormant cancer cells.
Application
Scientists at the ICT have discovered a novel pro-survival protein called TDIF in dormant cancers cells. Dormancy specific modification to TDIF is critical for the viability of dormant cancer cells. When TDIF blockers inhibit this modification in dormant cancer cells it leads to a high accumulation of DNA damage which leads to dormant cancer cell death, preventing their awakening. We have developed AI platform that can identify compounds to block this target. The team used AI methods to identify a series of small molecules that can inhibit this protein modification and demonstrated in vitro efficacy and selectivity in dormant cancer cell models. No effect on normal proliferating cells.
Benefits
Unlike current cancer therapies which also affect normal proliferative cells, our identified TDIF blocker affects only dormant cancer cells. The ambition is to develop a safe treatment that will reduce the incidence of recurrence/metastasis in a range of cancer types. A research team from the University of Pennsylvania and the Abramson Cancer Centre were funded to find and target dormant tumour cells before they can cause a recurrence of the disease. The team recently reported (2023) the results of a phase II clinical trial that showed – for the first time – it is possible to detect and treat dormant tumour cells in breast cancer survivors, offering a proof-of-concept for the strategy of preventing breast cancer recurrence.
IP Status and Investment Opportunity
Patent Status: Priority date (UK) 23rd August 2024.
Patent fully owned by UoB.
Seeking Investor/collaborator to further validate the target and progress from hit to lead. Potential spin-out company. Current grant applications include BCN & MRC in pipeline.