In short, we will identify genetic alterations that are neutral in normal cells, but that are lethal when combined with cancer mutations. This 'synthetic lethality' approach may identify potential therapeutic targets that are highly specific to the cancer cell. In the past year, we have made ...
Although synthetic lethality is not a new idea, recent advances, including CRISPR-based gene editing, have made possible systematic screens for synthetic lethal drug targets in human cancers. Such approaches have broad potential to drive the discovery of the next wave of genetic cancer targets and ...
With advances in genome sequencing, cancer treatments have increasingly sought to leverage the idea of “synthetic lethality,” exploiting cancer-specific genetic defects to identify targets that are uniquely essential to the survival of cancer cells. Synthetic lethality results when non-lethal mutation...
Susan Bates and Christina Annunziata looked at several recent papers on this form of treatment, which takes advantage of the synthetic lethality of BRCA (breast cancersusceptibility genes) and poly-ADP ribosepolymerase(PARP) proteins to attack cancerous cells whilst sparing healthy ones. BRCA and PAR...
The genetic concept of synthetic lethality has now been validated clinically through the demonstrated efficacy of poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of cancers in individuals with germline loss-of-function mutations in either BRCA1 or BRCA2. Three different PARP inhibitors...
cancer cell, leg A can continue to support the essential function and when leg A is drugged in a non-malignant cell, leg B will support the essential function. Synthetic lethality occurs in the cancer cell when leg A is drugged and leg B is mutated and both are thus unable to fulfil ...
Furthermore, it was found that reduction of EZH2 expression by antisense oligonucleotides (ASO) instead of an EZH2 inhibitor induces synthetic lethality in a variety of cancer cells with gain-of-function mutations of p53, such as partial breast cancer and prostate cancer. And there is no ...
Researchers Investigating a Class of Drugs that Could Short-Circuit Cancer Cells at Molecular Level For the past few years, drugs exploiting synthetic lethality have gained attention as novel anticancer agents. Breast and ovarian cancers with mutated BRCA1 or 2, essential components of a pathway for...
Abstract P215: The MDM2 inhibitor milademetan induces synthetic lethality in GATA3 mutant, ER positive breast cancer Background:AT-rich interactive domain 1A (ARID1A) is a tumor suppressor gene that is frequently mutated in gastric cancer (GC). Although ARID1A mutations a... V Tirunagaru,G...
The development of cancer therapies is limited by the availability of suitable drug targets. Potential candidate drug targets can be identified based on the concept of synthetic lethality (SL), which refers to pairs of genes for which an aberration in either gene alone is non-lethal, but co-oc...