Knighthood for Professor Stephen Jackson

his work has established many of the key principles by which cells respond to and repair DNA damage. This includes identifying many DNA-damage-response (DDR) proteins, establishing how they function, as well as how – in many cases – they are strongly evolutionarily conserved, and helping to define how their dysfunction yields cancer and other diseases.

In turn, these fundamental findings have been translated into innovation; Jackson has created three spin-out companies focused on the therapeutic opportunities arising from his research: KuDOS Pharmaceuticals, Mission Therapeutics and Adrestia Therapeutics.

The first, KuDOS, was founded in 1997 (and acquired by AstraZeneca in 2006) to develop Jackson’s observation that many DDR proteins represent attractive drug targets. Of the compounds KuDOS has brought forward, olaparib is the most advanced and has established a new cancer therapy paradigm, wherein a cancer cell’s genetic deficiency (such as the loss of BRCA1 or BRCA2 function) is exploited pharmacologically using a process called synthetic-lethality. This enables cancer cell killing with minimal impact to a patient’s normal cells. Olaparib, the first anti-cancer medicine targeted to patients based on them having an inherited predisposition, has now been approved for the treatment of ovarian, breast, prostate and pancreatic cancers.

Mission Therapeutics, co-founded in 2010, pursues new therapeutic opportunities arising from Jackson’s work on protein ubiquitylation and deubiquitylation. These are the processes by which ubiquitin, a small protein that occurs in all tissues, is attached or detached from another targeted protein. Since 2018, Adrestia Therapeutics has investigated potential drug targets for inherited rare diseases based on the concept of synthetic viability, a process by which a lethal or disease phenotype is “rescued”.