Signature 3: A New Hope for Gastric Cancer Patients

SIGNATURE 3, a specific genomic molecular fingerprint, represents a fresh avenue of investigation for physicians and researchers aiming to tackle gastrointestinal and other types of cancer. Gastric cancers are the third leading cause of cancer death in the world, not only because they are fairly common but also because they are incredibly difficult to treat. However, a new study shows that the signature 3 pattern of mutations, which is found in a significant proportion of breast, pancreatic, and ovarian cancers, is also present in approximately 10% of gastric cancers.

The signature 3 pattern of defects is associated with cells that have malfunctioning DNA repair mechanisms. This is advantageous in the targeting of cancer cells because, once attacked, these cells are unable to initiate DNA repair and will subsequently die. Cells displaying signature 3 are therefore vulnerable to platinum-based or poly(ADP-ribose) polymerase (PARP) inhibitor therapies, both of which target DNA repair. It is hoped that signature 3 can be used to predict which patients will demonstrate a response to these therapies.

Signature 3 defects are commonly associated with mutations in BRCA1 and BRCA2, although patients may display signature 3 defects without mutations in the BRCA genes. PARP inhibitors are a relatively new therapy that show promising results in the treatment of BRCA-related cancers. They have high specificity and are therefore more targeted than platinum-based drugs, with fewer associated side effects. Although they have yet to enter clinical trials in gastric cancer, they have proven extremely effective and safe in breast cancer trials and so it is hoped that they may receive approval for the treatment of other cancers relatively quickly.

“This is an extremely exciting finding which shows the importance of genomic sequencing for personalised healthcare in the future. In years to come, routine genomic analysis of cancers could show which have the signature 3 fingerprint and inform and transform [the] treatment of thousands of patients with these specific breast, ovarian, pancreatic, and gastric cancers,” stated one of the study authors, Prof Michael Stratton, Director, Wellcome Trust Sanger Institute, Hinxton, UK.

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