May 22, 2019   9:54pm
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Breakthrough for certain types of cancer…

We may be closer than we think to finding a tumor-stopping drug for those suffering from certain types of cancer …

According to Technology Review, “A drug tailor-made to strike at a tumor cell’s Achilles heel shrinks or stabilizes tumors in patients with certain treatment-resistant hereditary cancers while causing few side effects. The drug, called olaparib, is the first success story from a new and highly personalized approach to anticancer drug development. This strategy harnesses a concept known as synthetic lethality, in which a drug is designed to work in tandem with the molecular glitch underlying a specific kind of cancer.”

A small percentage of breast, ovarian, and prostate cancers are associated with defects in one copy of the BRCA1 or BRCA2 gene, which encode proteins that help proofread the genome during replication. If a BRCA-mutated cell happens to lose its one functional copy of the gene, proofreading is impaired, and mutations begin to accumulate as the cell divides. These mutations can cause a multitude of other cell processes to go awry, opening the door to tumor development.

Because there are several mechanisms for DNA repair, the loss of BRCA function doesn’t completely incapacitate a cell. But it does create a weakness not present in normal cells, which still carry a working copy of the BRCA gene. Olaparib targets that weakness by inhibiting an enzyme involved in another DNA proofreading pathway, generating a lethal double whammy to the cancer cell’s DNA while sparing healthy cells.

Of 19 patients with BRCA-associated cancer treated by olaparib in the trial, 12 experienced substantial and lasting stabilization or shrinkage of their tumors. “[The drug] was given as a single agent to treatment-resistant advanced cancers–these cancers shouldn’t respond to a piddly little enzyme inhibitor,” says Iglehart. “So the fact that it was so effective was very exciting to people.”

“The drug’s specificity means that unlike conventional chemotherapy drugs, which are toxic to normal cells and cancer cells alike, olaparib causes remarkably few side effects.”

Read the entire story inTechnology Review, “New Drug Kills Cancer with Few Side Effects,” Jocelyn Rice, June 25, 2009.

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