BioPathways is a monthly event series, presented by Rosalind Franklin University of Medicine and Science and SmartHealth Activator featuring prominent bioentrepreneurs, biotech executives and biotech venture capitalists in a fireside chat. We will also feature a guest biotech startup in a quick pitch. This month we are featuring Prof. Sarit Larisch, University of Haifa.

BACKGROUND

All cells in our body have the ability to self-destruct by activating an intrinsic cell death program called “apoptosis”. In this way, the accumulation of damaged and potentially dangerous cells, such as tumor cells, is greatly limited.

Unfortunately, cancer cells can acquire resistance towards cell death by inactivating cell suicide pathways, thereby gaining the ability for “unlimited” life and propagation. However, the ability to undergo apoptosis is not completely lost in cancer cells and most currently used anti-cancer therapies (chemotherapy, radiation) act by activating this apoptosis death pathway in cancer cells.

ARTS-induced tumor cell death R&D

Prof. Sarit Larisch’s lab focuses on investigating the molecular mechanisms of cell death, specifically how abnormal regulation of this process contributes to the transformation of healthy cells into cancers. She is using this knowledge to construct molecular tools that will enforce cancer cells to selectively self-destruct.

Prof. Larisch discovered a protein she termed ARTS (Sept4_i2).ARTS functions at the apex of the cascade of events which culminates in the death of cells. Indeed, we have found that many types of cancers lose the expression of ARTS, thereby avoid cell death and can propagate in an uncontrolled manner. ARTS promotes cell death by degrading two major inhibitors of apoptosis proteins; Bcl-2 and XIAP which prevent the execution of cell death. Many types of cancers express high levels of both XIAP and BCL-2 and they become “addicted” to high levels of these inhibitors, which allow them to escape death. Accordingly, both XIAP and Bcl-2 have become targets for developing anti-cancer drugs.

We have now identified small molecules which mimic the function of ARTS. These “ARTS mimetic” molecules enter cancer cells and degrade both inhibitor proteins Bcl-2 and XIAP. Reducing the levels of inhibitors enforces the execution of cell death in cancer cells. As healthy cells maintain relatively low levels of inhibitors, administration of ARTS-mimetic small molecule should not harm normal cells but selectively kill cancer cells. These small molecules are unique. No other anti-cancer drugs target BOTH these inhibitors for degradation. We are now in the process of developing these ARTS mimetics into a novel class of distinct potent anti-cancer therapies.