Can­cer trails dom­i­nate $36m fund­ing

Nine re­searchers will share $36 mil­lion from Aus­tralia’s top re­search fund­ing body — its most valu­able l grants so far — for work into can­cer and other dis­eases. Lyn­nette Hoff­man re­ports

The Weekend Australian - Travel - - Health -

NO tears are shed, you won’t find any notes, and no pre­ven­tion pro­grams are in place, but ev­ery sec­ond a mil­lion of your body’s mil­lion bil­lion cells com­mit sui­cide. They’re equipped with a built-in self-de­struct mode — and while this may not sound like such a good thing, it is.

Cells are pro­lific breed­ers and as a mil­lion cells die, a mil­lion other cells are di­vid­ing in two. In a healthy per­son, the self-de­struct mode keeps things bal­anced. Can­cer cells, on the other hand, are prac­ti­cally im­mor­tal.

Pro­fes­sor David Vaux of La Trobe Univer­sity has been study­ing the in­tri­cate process of

cell sui­cide’’, tech­ni­cally known as apop­to­sis, since the 1980s. If a gene is dam­aged in a cell so that it can no longer op­er­ate the self­de­struct mech­a­nism, that cell, and all its prog­eny, will per­sist, and can even­tu­ally turn into a tu­mour,’’ Vaux says.

By pin­point­ing those genes that stop cells from killing them­selves and search­ing for ways to switch them off, Vaux and other re­searchers are clos­ing in on new, hope­fully less toxic ways to treat can­cer by tar­get­ing the spe­cific genes that cause the dis­ease.

The first big break came in 1988 when study­ing fol­lic­u­lar lym­phoma, a com­mon can­cer of the white blood cells. Vaux dis­cov­ered that when a gene called Bcl-2 was turned on, the cells couldn’t kill them­selves.

‘‘ The dam­age be­gan with a sin­gle white blood cell where two chro­mo­somes broke, but were re­paired by the cell the wrong way around,’’ Vaux says. ‘‘ That ac­ti­vated a gene called Bcl-2, and the Bcl-2 pro­tein turned out to be an in­hibitor of the self-de­struct process — like a pin in a hand grenade,’’ he says.

A drug de­signed to ‘‘ in­hibit the in­hibitor’’ is cur­rently in the first phase of clin­i­cal tri­als.

Mean­while, an­other fam­ily of pro­teins called IAPs (which stands for in­hibitors of apop­to­sis pro­teins) have been shown to stop can­cer­ous cells from dy­ing in liver can­cer, cer­vi­cal can­cer, some lung can­cers and melanoma — and re­searchers have dis­cov­ered a pro­tein called Smac that in­hibits the IAPs. Sev­eral phar­ma­ceu­ti­cal com­pa­nies are de­vel­op­ing drugs that mimic it.

So far the re­sults are promis­ing. In mice the

‘‘‘‘drugs have caused the can­cer cells to self­de­struct, while nor­mal cells have es­caped un­harmed — al­though it’s too soon to say whether the drugs will work in peo­ple.

There is still masses of re­search to be done, as sci­en­tists have only iden­ti­fied a few of the un­der­ly­ing ge­netic causes of a tiny amount of can­cers. But this week Vaux was awarded a $4 mil­lion Aus­tralia Fel­low­ship to fur­ther his study over the next five years.

The award was one of nine dis­trib­uted by the Na­tional Health and Med­i­cal Re­search Coun­cil to fund re­search in the ar­eas of can­cer, in­fec­tious dis­ease and men­tal health. Nearly half of $36 mil­lion in fund­ing will go to­ward the fight against can­cer. Pro­fes­sor John Hop­per of the Univer­sity of Melbourne is also look­ing at the way genes in­flu­ence can­cer — fo­cus­ing on the way genes make you more or less vul­ner­a­ble to var­i­ous en­vi­ron­men­tal risk fac­tors.

Hop­per and his col­leagues have de­vel­oped one of the world’s most ex­ten­sive long-term data­bases which fol­lows Aus­tralians with breast can­cer and col­orec­tal can­cer, their fam­i­lies, and con­trol groups who don’t have can­cer. The data in­cludes blood sam­ples, tis­sue sam­ples, in­for­ma­tion on their life­styles in­clud­ing fac­tors such as smok­ing and ex­er­cise, med­i­ca­tion and treat­ment his­tory.

Hop­per’s re­search has put a hole in the no­tion that en­vi­ron­men­tal and lifestyle fac­tors have the same im­pact on dis­ease risk in all peo­ple. De­pend­ing on your ge­netic make-up, you may be much more or much less vul­ner­a­ble to cer­tain en­vi­ron­men­tal fac­tors than some­one with a dif­fer­ent ge­netic makeup, Hop­per says.

For ex­am­ple, women who have in­her­ited a ge­netic fault in ei­ther of two key breast can­cer genes may be twice as likely to de­velop breast can­cer if they smoke cig­a­rettes — but smok­ing doesn’t seem to in­crease breast can­cer risk in other women who have not in­her­ited a fault in ei­ther of the genes.

In other cases, the re­searchers have found pub­lic health ben­e­fits they hadn’t ex­pected. For ex­am­ple, oral con­tra­cep­tives seem to help pro­tect women against breast can­cer if they carry a fault in the BRCA1 gene, which in­creases a wo­man’s risk of the dis­ease. But for women with­out the ge­netic fault, the con­tra­cep­tives have lit­tle or no ef­fect.

Ev­ery­one isn’t born equal when it comes to dis­ease risk, es­pe­cially when it comes to com­mon can­cers like those of the breast, bowel and prostate,’’ Hop­per says. Knowl­edge is power and know­ing your ge­netic risk may al­low you make bet­ter life de­ci­sions.’’

The re­search is also shed­ding light on the most ef­fec­tive ways to screen peo­ple for ge­netic risks. The norm has been for only peo­ple with very strong fam­ily his­to­ries to be screened — but fam­ily his­tory isn’t as strong a pre­dic­tor as com­monly thought. Less than a third of that group car­ries a ge­netic fault.

Hop­per says it may be more cost-ef­fec­tive to fo­cus on screen­ing peo­ple with early-on­set can­cer in­stead. Tu­mour sam­ples can be ex­am­ined un­der a mi­cro­scope to look for tell­tale signs that the can­cer has been caused by a ge­netic fault. If that’s the case, the pa­tient can then be of­fered ge­netic test­ing. If ge­netic mu­ta­tions are in­deed found, rel­a­tives can be alerted that they may be at a high-risk of can­cer as well, and pa­tients can be mon­i­tored closely for fu­ture can­cers, Hop­per says.

But abil­ity to pre­dict risks still hinges on re­searchers de­vel­op­ing a bet­ter un­der­stand­ing of the ge­netic as­pects of can­cers, he says.

Can­cer isn’t the only hot topic cov­ered by re­cip­i­ents of the fel­low­ship, how­ever.

La Trobe Univer­sity’s Tony McMichael is mea­sur­ing the im­pact of cli­mate change and en­vi­ron­men­tal in­flu­ences on pub­lic health risks in Aus­tralia and abroad.

He says ev­ery­thing from in­creased cases of sal­mo­nella poi­son­ing to in­creases in death, ill­ness and in­jury from heat­waves, storms, floods and bush­fires are al­ready be­ing doc­u­mented in Aus­tralia.

Mos­quito-borne ill­nesses such as dengue fever are ex­tend­ing fur­ther south in Aus­tralia, and over­seas the ef­fects of cli­mate change on dis­ease are even more ob­vi­ous.

Malaria is mov­ing to higher al­ti­tudes in East Africa and parts of South Amer­ica, tick-borne en­cephali­tis is spread­ing north in Swe­den as tick pop­u­la­tions move north, and cholera is in­creas­ing in coastal ar­eas of Bangladesh as the com­bi­na­tion of warmer wa­ters and in­dus­trial runoff cre­ates a per­fect bac­te­rial breed­ing ground.

Like other re­cip­i­ents, McMichael’s re­search will also in­volve de­vel­op­ing po­ten­tial so­lu­tions to coun­ter­act the prob­lem. Since the cli­mate change ge­nie is al­ready partly out of the bot­tle, we must also de­vise ways of adapt­ing and less­en­ing ad­verse im­pacts,’’ he says.

Fel­low­ship re­cip­i­ents each re­ceive $800,000 an­nu­ally over five years.

Pic­ture: David Crosling

Boost: La Trobe Univer­sity’s David Vaux is one of nine re­search fund­ing win­ners

Newspapers in English

Newspapers from Australia

© PressReader. All rights reserved.