Combination of two drugs disrupts cancer cells' ability to survive DNA damage, study finds

Medical News | October 14, 2019

Combination of two drugs disrupts cancer cells' ability to survive DNA damage, study finds
In continuing efforts to find novel ways to kill cancer cells, researchers at the University of Maryland School of Medicine (UMSOM) have identified a new pathway that leads to the destruction of cancer cells. The new finding, recently published in the journal PNAS, could pave the way for the broader use of a class of anticancer drugs already on the market. These drugs, known as PARP inhibitors, are currently approved by the FDA to treat only a limited group of breast and ovarian cancers associated with BRCA gene mutations. In a proof of concept study, the researchers demonstrated that combining a PARP inhibitor with a DNA methyltransferase (DNMT) inhibitor delivered a one-two punch to non-small cell lung cancer tumors, which are normally not associated with mutations in BRCA genes. The research, conducted in mouse models and cell lines, outlines the mechanistic action of the combination. The DNMT inhibitor triggers an effect that mimics a BRCA mutation in the cancer cell so the cell responds to the lethal effects of the PARP inhibitor, which prevents repair of damage to a tumor cell's DNA, triggering cell death. Those who inherit two copies of a normal BRCA gene enjoy protection from DNA damage that can cause healthy cells to turn malignant. Those who inherit a mutation in this gene, however, have a higher risk of breast and ovarian cancer (in women) and prostate cancer (in men). Researchers have previously demonstrated that tumors that share molecular features of BRCA-mutant tumors – those with so-called "BRCAness" – respond to PARP inhibitor drugs designed to target tumors that arise from BRCA mutations. This new study from UMSOM is the first to demonstrate that cells can be induced to have a BRCAness phenotype or gene expression that is not the result of a mutation by treating them with the DNA methyltransferase inhibitor drug.

Spotlight

Different types of clinical studies are used in different circumstances. Depending on what is known and what isn’t, scientists may even study the same research question using different kinds of studies and in different groups of people. Here are different types of clinical studies and why they might be used.

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Guerbet (GBT) to sale its pharmaceutical site in Montreal (Canada) to MedXL

Guerbet, MedXL | July 16, 2020

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Spotlight

Different types of clinical studies are used in different circumstances. Depending on what is known and what isn’t, scientists may even study the same research question using different kinds of studies and in different groups of people. Here are different types of clinical studies and why they might be used.