An underlying hallmark of cancers is genomic instability and a greater propensity to accumulate DNA damage. Historical cancer therapy by radiotherapy and DNA-damaging chemotherapy is based on this principle but is accompanied by significant collateral damage to normal tissue and unwanted side effects. Targeted therapy based on inhibiting the DNA damage response (DDR) in cancers offers the potential for a greater therapeutic window by tailoring treatment to patients with tumors lacking specific DDR functions.

The DNA damage response (DDR) in cancer cells differs in at least four aspects compared to those of normal cells, namely the loss of one or more DDR pathway or capability leading to greater sensitivity to DNA damaging agents, increased levels of replication stress, increased potential for immune priming and the potential for a DDR dependency that could lead to sensitivity to a single DDR agent. An example of the latter is the synthetic lethality and clinical activity of PARP inhibitors in tumours with homologous recombination repair deficiencies such as BRCA mutant cancers.

This meeting will focus on the current approaches of targeting DDR to generate new cancer therapies from building on the clinical success of PARP inhibitors, identifying ways to exploit replication stress in cancers, enhance the potential for immunotherapy combinations as well as enhance the activity of targeted DNA damaging agents such as antibody drug conjugates (ADCs) and radioconjugates.

The meeting aims to bring together academics, translational biologists and clinicians who are working towards developing therapies based on targeting DDR in cancer and represents an excellent opportunity for networking and gaining broader insights into this exciting area of cancer biology and therapeutics through a number of panel discussions as well as presentations.

Key Sessions

• Current status of DDR therapeutics
• Building on the success of PARP inhibitors
• DDR therapeutic approaches based on DDR synthetic lethality
• Targeting replication stress in cancers
• Combining DDR inhibition with DNA damaging agents (chemotherapy/ADCs and potentiation of radiation/radio-conjugates)
• Combining DDR inhibitors with immunotherapy
• Enabling capabilities for DDR therapeutics
• The next generation of DDR new targets

Panel Discussions

• Challenges of therapeutic preclinical and clinical development
• Patient stratification and optimisation of drug safety /therapeutic index
• Career options in DDR drug discovery and development

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