Currently, effective therapies for breast cancer are lacking. ATM is an attractive target for cancer treatment. Previous studies suggested a synthetic lethality between PTEN and PARP. However, the synthetically lethal interaction between PTEN and ATM in breast cancer has not been reported. Moreover, ...
In recent years, synthetic lethality has been recognized as a solid paradigm for anticancer therapies. The discovery of a growing number of synthetic lethal targets has led to a significant expansion in the use of synthetic lethality, far beyond poly(ADP-ribose) polymerase inhibitors used to ...
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 ...
Furthermore, upregulation of PARP activity is essential for the survival of prostate cancer cells and we demonstrate a synthetic lethality between ADT and PARP inhibition in vivo. Our data suggest that ADT can functionally impair HR prior to the development of castration resistance and that, this ...
The concept of synthetic lethality applies to pairs of genes whose functional loss can be tolerated singly but not in combination.[4] Tumour suppressor genes, which control cell growth, are often deleted or mutated in cancer cells allowing them to sustain uncontrolled growth.[4] Because the funct...
Similarly, combination of two non-cytotoxic compounds, the rapamycin analog everolimus and an ATP-competitive mTOR inhibitor dactolisib, showed synthetic lethality in several mTOR-addicted cell lines. Taken together, by studying the combination of cytotoxic and cytostatic drug responses, we identified ...
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...
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 ...
The mechanisms underlying lethality between BRCA1/2 deficiency, 53BP1 loss and Polθ targeting are emerging but currently unclear. HR and TMEJ repair mechanisms share a substrate of resected, single-stranded DNA (ssDNA) 3’ ends, and may compete2,9. In HR-deficient cells, Polθ targeting is...
Figure 2. Synthetic lethality and poly(ADP-ribose) polymerase (PARP) inhibitors.Synthetic lethality using a poly(ADP-ribose) polymerase (PARP) inhibitor in cells with a breast cancer-associated (BRCA) gene mutation (top panel). Escape from PARP inhibitor-induced synthetic lethality (middle panel)...