Multi-use prostate can­cer test paves way for one-off treat­ments

The Guardian - - NATIONAL - Press As­so­ci­a­tion

A rev­o­lu­tion­ary three-in-one blood test could pave the way to pre­ci­sion-per­son­alised treat­ment for ad­vanced prostate can­cer. The test has the po­ten­tial to trans­form the way the dis­ease is tack­led by tar­get­ing spe­cific gene mu­ta­tions, it is claimed.

By look­ing for can­cer DNA in blood sam­ples, re­searchers were able to iden­tify men with de­fec­tive BRCA genes who were likely to ben­e­fit from a class of drugs called PARP in­hibitors.

They also used the test to mon­i­tor DNA in the blood af­ter treat­ment started, so pa­tients who were not re­spond­ing could quickly be switched to an al­ter­na­tive ther­apy. The same test was used to pick up signs of evolv­ing can­cer show­ing the first signs of drug re­sis­tance.

Prof Jo­hann de Bono, who led the team at the In­sti­tute of Can­cer Re­search in Lon­don, said: “We think it could be used to make clin­i­cal de­ci­sions about whether a PARP in­hibitor is work­ing within as lit­tle as four to eight weeks of start­ing ther­apy.

“Not only could the test have a ma­jor im­pact on treat­ment of prostate can­cer, but it could also be adapted to open up the pos­si­bil­ity of pre­ci­sion medicine to pa­tients with other types of can­cer.”

The test could al­low the PARP in­hibitor ola­parib to be­come a stan­dard treat­ment for ad­vanced prostate can­cer, by tar­get­ing those most likely to ben­e­fit, pick­ing up early signs that the drug might not be work­ing and mon­i­tor­ing for emerg­ing re­sis­tance. PARP in­hibitors block an en­zyme used by can­cer cells with de­fec­tive BRCA 1 and 2 genes to re­pair their DNA. When PARP is dis­abled, the cells die.

The drugs do not gen­er­ally work on can­cer cells with func­tion­ing BRCA genes be­cause th­ese are pri­mary DNA re­pair tools that make PARP un­nec­es­sary. While some pa­tients re­spond to the drugs for years, others ei­ther fail to re­spond at an early stage or de­velop re­sis­tant can­cer.

The new test, de­scribed in the jour­nal Can­cer Dis­cov­ery, was de­vel­oped with the help of 49 pa­tients en­rolled in a clin­i­cal trial in­ves­ti­gat­ing the ef­fec­tive­ness of ola­parib. Men re­spond­ing to the drug were found to ex­pe­ri­ence an av­er­age drop in cir­cu­lat­ing can­cer DNA of 49.6% af­ter eight weeks of treat­ment. Pa­tients whose can­cer DNA blood lev­els were low­ered by ola­parib sur­vived an av­er­age of 17 months com­pared with 10.1 months for those whose lev­els re­mained high.

The sci­en­tists also con­ducted a de­tailed in­ves­ti­ga­tion of the ge­netic changes in can­cer DNA among men who stopped re­spond­ing to ola­parib. They found that the cells ac­quired ge­netic changes that can­celled out the DNA re­pair de­fects mak­ing them sus­cep­ti­ble to the drug.

Prof Paul Work­man, chief ex­ec­u­tive of the in­sti­tute, said: “Blood tests for can­cer promise to be truly rev­o­lu­tion­ary. They are cheap and sim­ple to use but most im­por­tantly, be­cause they aren’t in­va­sive, they can be em­ployed or ap­plied to rou­tinely mon­i­tor pa­tients to spot early if treat­ment is fail­ing – of­fer­ing pa­tients the best chance of sur­viv­ing their dis­ease.

“This test is par­tic­u­larly ex­cit­ing be­cause it is multi-pur­pose, de­signed for use both be­fore and af­ter treat­ment,” he said. “We be­lieve it can usher in a new era of pre­ci­sion medicine for prostate can­cer.”

Each year, about 47,000 men in the UK are diagnosed with prostate can­cer, and more than 11,000 die from the dis­ease.

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