Synthetic lethality: A new way to kill cancer cells

Feb 22, 2010
This shows the mechanism of sensitivity to PARP inhibition in BRCA-deficient cells. Credit: Susan E Bates

Ovarian and breast cancer treatments being developed that mix a protein inhibitor and traditional anticancer drugs are showing signs of success, according to a new review for Faculty of 1000 Biology Reports.

Susan Bates and Christina Annunziata looked at several recent papers on this form of treatment, which takes advantage of the synthetic lethality of BRCA ( susceptibility genes) and poly-ADP ribose (PARP) proteins to attack cancerous cells whilst sparing healthy ones.

BRCA and PARP are two key players in and have different but complementary functions in the cell. Loss of the BRCA protein still allows the cell to survive but greatly increases its chances of becoming cancerous through the accumulation of mutations. The loss of both proteins, however, kills the cell in a process called synthetic lethality.

Researchers, by using drugs to block the activity of PARP in cells missing BRCA, such as those found in certain breast and ovarian cancers, can help spare healthy, non-cancerous cells because they have functional BRCA and are not affected by the loss of PARP. Thus, only without functional BRCA protein are killed by drugs that inhibit PARP.

Recent clinical trials have shown that cancers caused by mutations that knock out BRCA activity can be controlled by blocking PARP activity with specific drugs. Patients were treated with traditional alone or in combination with one of two new PARP inhibitors, olaparib or BSI-201.

Bates notes that patients on combination therapy had improved "[disease] progression-free survival, and overall survival" as compared to patients treated with traditional drugs alone.

Bates is optimistic about the promise of combining PARP inhibitors with existing . She says that the results of these clinical trials "have provided proof of principle in achieving synthetic lethality" with PARP-inhibiting drugs and that treatments combining novel PARP inhibitors with traditional chemotherapeutic drugs have the potential to vanquish BRCA-associated breast and ovarian cancers.

Explore further: Immune cells can promote liver cancer

More information: The full text of this article is available for subscribers at f1000biology.com/reports/10.3410/B2-10/ or for reporters at faculty1000.files.wordpress.com/2010/02/bates-report.pdf

Related Stories

New therapies to treat breast, lymph cancer: studies

Jun 01, 2009

New therapies developed following groundbreaking clinical trials appear to effectively target breast cancer and non-Hodgkin's lymphoma, according to research unveiled Sunday at a major cancer conference.

Recommended for you

DNA blood test detects lung cancer mutations

16 hours ago

Cancer DNA circulating in the bloodstream of lung cancer patients can provide doctors with vital mutation information that can help optimise treatment when tumour tissue is not available, an international group of researchers ...

Tumors prefer the easy way out

19 hours ago

Tumor cells become lethal when they spread. Blocking this process can be a powerful way to stop cancer. Historically, scientists thought that tumor cells migrated by brute force, actively pushing through whatever ...

Brain tumors may be new targets of Ebola-like virus

19 hours ago

Brain tumors are notoriously difficult for most drugs to reach, but Yale researchers have found a promising but unlikely new ally against brain cancers—portions of a deadly virus similar to Ebola.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.