An artificial mole as an early warning sign April 23, 2018, 11:23

Along­side car­dio­vas­cu­lar dis­ease, can­cer has be­come the top cause of death in in­dus­tri­alised coun­tries. Many of those af­fected are di­ag­nosed only af­ter the tu­mour has de­vel­oped ex­ten­sively. This of­ten re­duces the chance of re­cov­ery sig­nif­i­cantly: the cure rate for prostate can­cer is 32 per­cent and only 11 per­cent for colon can­cer. The abil­ity to de­tect such tu­mours re­li­ably and early would not only save lives, but also re­duce the need for ex­pen­sive, stress­ful treat­ment.

Re­searchers work­ing with Mar­tin Fusseneg­ger, Pro­fes­sor at the De­part­ment of Biosys­tems Sci­ence and En­gi­neer­ing at ETH Zurich in Basel, have now pre­sented a pos­si­ble so­lu­tion for this prob­lem: a syn­thetic gene net­work that serves as an early warn­ing sys­tem. It recog­nises the four most com­mon types of can­cer – prostate, lung, colon and breast can­cer – at a very early stage, namely when the level of cal­cium in the blood is el­e­vated due to the de­vel­op­ing tu­mour.

De­railed cal­cium bal­ance trig­gers melanin pro­duc­tion

The early warn­ing sys­tem com­prises a ge­netic net­work that biotech­nol­o­gists in­te­grate into hu­man body cells, which in turn are in­serted into an im­plant. This en­cap­su­lated gene net­work is then im­planted un­der the skin where it con­stantly mon­i­tors the blood cal­cium level.

As soon as the cal­cium level ex­ceeds a par­tic­u­lar thresh­old value over a longer pe­riod of time, a sig­nal cas­cade is trig­gered that ini­ti­ates pro­duc­tion of the body’s tan­ning pig­ment melanin in the ge­net­i­cally mod­i­fied cells. The skin then forms a brown mole that is vis­i­ble to the naked eye.

The mole ap­pears long be­fore the can­cer be­comes de­tectable through con­ven­tional di­ag­no­sis. “An im­plant car­rier should then see a doc­tor for fur­ther eval­u­a­tion af­ter the mole ap­pears,” ex­plains Fusseneg­ger. It is no rea­son to panic. “The mole does not mean that the per­son is likely to die soon,” stresses the ETH pro­fes­sor. It sim­ply means that clar­i­fi­ca­tion and if nec­es­sary treat­ment are needed.

The re­searchers used cal­cium as the in­di­ca­tor of the de­vel­op­ment of the four types of can­cer, as it is reg­u­lated strongly in the body. Bones serve as a buffer that can bal­ance out con­cen­tra­tion dif­fer­ences. How­ever, when too much cal­cium is de­tected in the blood, this may serve as a sign for one of the four can­cers.

Early de­tec­tion in­creases sur­vival rate

“Early de­tec­tion in­creases the chance of sur­vival sig­nif­i­cantly,” says Fusseneg­ger. For ex­am­ple, if breast can­cer is de­tected early, the chance of re­cov­ery is 98 per­cent; how­ever, if the tu­mour is di­ag­nosed too late, only one in four women has a good chance of re­cov­ery. “Nowa­days, peo­ple gen­er­ally go to the doc­tor only when the tu­mour be­gins to cause prob­lems. Un­for­tu­nately, by that point it is of­ten too late.”

The im­plant also has an ad­di­tional ad­van­tage: “It is in­tended pri­mar­ily for self-mon­i­tor­ing, mak­ing it very cost ef­fec­tive,” ex­plains the ETH pro­fes­sor. How­ever, for those who would pre­fer not to deal with the con­stant stress, an im­plant can also be used that de­vel­ops a mark vis­i­ble only un­der a red light. “This reg­u­lar check could be car­ried out by their doc­tor.”

The dis­ad­van­tage is that the ser­vice life of such an im­plant is lim­ited, as Fusseneg­ger has found in lit­er­a­ture. “En­cap­su­lated liv­ing cells last for about a year, ac­cord­ing to other stud­ies. Af­ter that, they must be in­ac­ti­vated and re­placed.”

A re­li­able pro­to­type

So far, this early warn­ing im­plant is a pro­to­type; the as­so­ci­ated work re­cently pub­lished in the jour­nal Sci­ence Trans­la­tional Med­i­cine is a fea­si­bil­ity study. The re­searchers have tested their early warn­ing sys­tem in a mouse model and on pig skin. It func­tioned re­li­ably dur­ing these tests. Moles de­vel­oped only when the cal­cium con­cen­tra­tion reached a high level.

The Basel-based sci­en­tists still have a long way to go be­fore hu­man test­ing can be­gin. “Con­tin­ued de­vel­op­ment and clin­i­cal tri­als in par­tic­u­lar are la­bo­ri­ous and ex­pen­sive, which we as a re­search group can­not af­ford,” says the ETH pro­fes­sor. How­ever, he would like to pro­mote the trans­la­tion of his de­vel­op­ments, so that one day they will lead to ap­plic­a­ble prod­ucts. He es­ti­mates that bring­ing such a can­cer di­ag­no­sis im­plant to mar­ket ma­tu­rity will take at least ten years of re­search and de­vel­op­ment.

The con­cept of the “bio­med­ical tat­too”, as Fusseneg­ger de­scribes this new find­ing, would also be ap­plic­a­ble to other grad­u­ally de­vel­op­ing ill­nesses, such as neu­rode­gen­er­a­tive dis­eases and hor­monal dis­or­ders. In prin­ci­ple, the re­searchers could re­place the mol­e­c­u­lar sen­sor to mea­sure bio­mark­ers other than cal­cium.