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JOIN OUR EFFORTS TO

Design the next generation of synthetic lethality

by launching a science company.

Most oncogenic alterations in humans (mutations, translocations, amplifications, deletions, and epigenetic modifications) are caused by the inefficient repair of damaged DNA. These errors occur at a rate of around 10,000 a day mainly due to genotoxic insults from endogenous reactive oxygen species (ROS). This is a disease of aging, it is only a matter of time before cellular repair machinery fails to catch an error, or more typically miss-repairs it, and this leads to the development of a population of cells with oncogenic potential.

One of the highest potential avenues of investigation in oncology at the moment is targeting deficiencies in cellular DNA repair machinery that are unique to cancerous cells. Tumor cell deficiency in tumor suppressor gene p53 has long been a target to increase sensitivity to DNA damaging therapeutics ranging from cisplatin to radiotherapy. This is because, by comparison, normal cells are better able to repair, although unfortunately this still drives damage and further tumors.

More recently ‘synthetic lethality’ has emerged as a more advanced method of leveraging cancer’s greatest strength; the lack of checks on DNA, against it. This adds a layer of selectivity (or logical computation) to therapeutics by targeting non-druggable cancer-promoting lesions with pharmacological inhibition of the druggable synthetic lethal interactor. In theory this should select exclusively cancer cells, and be well tolerated by healthy normal cells, that lack the cancer-specific mutation. Impressive clinical results have already been achieved with PARP inhibitors (PARP enzyme repairs double stranded breaks) in patients with BRCA1/2-mutated cancers (BRCA repairs double stranded breaks), including ovarian, breast and prostate cancers. 

The ability to add this level of selectivity in what to date has been a brute force approach is really exciting but it’s still far from perfect. The best results so far are in breast cancer, where patients that have this mutation had a 33% response rate, much better than other therapeutics, but 67% still died and the long-term outcome remains to be seen.

Our concern is that we are about to start another long journey of identifying targets, in which it might work in 1/3rd of patients, whilst the very nature of the genomic instability and population heterogeneity of cancer means that there is probably a way around any single point weakness. We are starting with the question of how can we detect abnormalities in DNA, mediators and effectors, not by sequential target discovery and development, but by equipping the therapeutic with the inherent ability to discriminate between overall normal and states which have oncogenic potential.

Clearly all of these are moon-shot projects in themselves, with thousands of people already working in these areas and billions of pounds in research funding. We hope that our approach of bringing together diverse fields, and often asking the non-obvious questions, can create new directions that might play some small part to accelerate the goal of eradicating cancer.

our offer

You will join our in-house team of entrepreneurial scientists as a ‘Founding Analyst’ to lead opportunity analysis and venture creation in this particular area. Specifically, you will focus on mapping out the constraints and limitations currently leading to a lack of innovation, and team building.

Our partnership with Cancer Research UK means that your work will also be supported by the world’s largest independent funder of cancer research. Further information about the DSV-CRUK programme here.

After six to nine months, it’s anticipated that you will co-found up to three start-ups in this space, taking the role of CEO or CTO at one. Each company will be created with £50,000 to cover initial proof of principle work. DSV may follow on up to £500,000 and Cancer Research UK is launching several seed, grant and later stage funding initiatives that may be relevant on a case by case basis.

Most oncogenic alterations in humans (mutations, translocations, amplifications, deletions, and epigenetic modifications) are caused by the inefficient repair of damaged DNA. These errors occur at a rate of around 10,000 a day mainly due to genotoxic insults from endogenous reactive oxygen species (ROS). This is a disease of aging, it is only a matter of time before cellular repair machinery fails to catch an error, or more typically miss-repairs it, and this leads to the development of a population of cells with oncogenic potential.

One of the highest potential avenues of investigation in oncology at the moment is targeting deficiencies in cellular DNA repair machinery that are unique to cancerous cells. Tumor cell deficiency in tumor suppressor gene p53 has long been a target to increase sensitivity to DNA damaging therapeutics ranging from cisplatin to radiotherapy. This is because, by comparison, normal cells are better able to repair, although unfortunately this still drives damage and further tumors.

More recently ‘synthetic lethality’ has emerged as a more advanced method of leveraging cancer’s greatest strength; the lack of checks on DNA, against it. This adds a layer of selectivity (or logical computation) to therapeutics by targeting non-druggable cancer-promoting lesions with pharmacological inhibition of the druggable synthetic lethal interactor. In theory this should select exclusively cancer cells, and be well tolerated by healthy normal cells, that lack the cancer-specific mutation. Impressive clinical results have already been achieved with PARP inhibitors (PARP enzyme repairs double stranded breaks) in patients with BRCA1/2-mutated cancers (BRCA repairs double stranded breaks), including ovarian, breast and prostate cancers. 

The ability to add this level of selectivity in what to date has been a brute force approach is really exciting but it’s still far from perfect. The best results so far are in breast cancer, where patients that have this mutation had a 33% response rate, much better than other therapeutics, but 67% still died and the long-term outcome remains to be seen.

Our concern is that we are about to start another long journey of identifying targets, in which it might work in 1/3rd of patients, whilst the very nature of the genomic instability and population heterogeneity of cancer means that there is probably a way around any single point weakness. We are starting with the question of how can we detect abnormalities in DNA, mediators and effectors, not by sequential target discovery and development, but by equipping the therapeutic with the inherent ability to discriminate between overall normal and states which have oncogenic potential.

Clearly all of these are moon-shot projects in themselves, with thousands of people already working in these areas and billions of pounds in research funding. We hope that our approach of bringing together diverse fields, and often asking the non-obvious questions, can create new directions that might play some small part to accelerate the goal of eradicating cancer.

our offer
You will join our in-house team of entrepreneurial scientists as a ‘Founding Analyst’ to lead opportunity analysis and venture creation in this particular area. Specifically, you will focus on mapping out the constraints and limitations currently leading to a lack of innovation, and team building.
Our partnership with Cancer Research UK means that your work will also be supported by the world’s largest independent funder of cancer research. Further information about the DSV-CRUK programme here.
After six to nine months, it’s anticipated that you will co-found up to three start-ups in this space, taking the role of CEO or CTO at one. Each company will be created with £50,000 to cover initial proof of principle work. DSV may follow on up to £500,000 and Cancer Research UK is launching several seed, grant and later stage funding initiatives that may be relevant on a case by case basis.
the ideal profile for this opportunity will have experience in a mix of the following areas:

Tumor suppressors, promoters and tumorigenesis, oncogenes, the malignant / DNA damage threshold, DNA damage and cell cycle checkpoints, nucleotide excision repair (NER), base excision repair (BER) and mismatch repair (MMR), transcription coupled variants of these, DNA verification, damage sensing, damage mediators and repair.

Ideally this would be coupled with knowledge of genetic reprogramming techniques that could transiently or permanently affect these systems whilst smartly affecting the system only in appropriate states. A background in complexity science, systems biology, genome analysis or in silico modelling may also help to model such systems and design therapeutics accordingly.

the ideal profile for this opportunity will have experience in a mix of the following areas:

Tumor suppressors, promoters and tumorigenesis, oncogenes, the malignant / DNA damage threshold, DNA damage and cell cycle checkpoints, nucleotide excision repair (NER), base excision repair (BER) and mismatch repair (MMR), transcription coupled variants of these, DNA verification, damage sensing, damage mediators and repair.

Ideally this would be coupled with knowledge of genetic reprogramming techniques that could transiently or permanently affect these systems whilst smartly affecting the system only in appropriate states. A background in complexity science, systems biology, genome analysis or in silico modelling may also help to model such systems and design therapeutics accordingly.

Applications close November 30th!

Interviews start from 18th of October with places allocated as soon as the right fit is found.

Applications close November 30th!

Interviews start from 18th of October with places allocated as soon as the right fit is found.