featuring :teenage bombers against the …...featuring :teenage bombers against the russians, and...

FEATURING :Teenage bombers against the Russians, and the Pirelli Calendar pictures that went too far

r: suNnAyTIrdlEsmagazInJune 19, 2005

One of the world's top

specialists has justdeclared a cancer

breakthrough: 'TheSe

are the most stunningresults. The findings

are astonishing

beyond belief. A newS

age now begins:

We've heard it all

before - or have we?

PDF compression, OCR, web optimization using a watermarked evaluation copy of CVISION PDFCompressor

http://www.cvisiontech.com/

Doctors believe they have found the drugsto sainsist they have the body of evidence to prove

HOW.THE WA

Cover Story

#nr nccS'es4'

a,. t,&' *-flt. a.-. Wn nvnw.-t.C,awa*.b- nv.'W #4r ., 'bA'r /t'.tw a 'A 4,4v .r -- -4- -a

for use in the UnitS ftageoffivernonths,frorn 156and could be available months to 20,3 months.am in about a year. The patients chosen for thetin.producedby6enen tria! already had advanced dis-on rapid approval from ease that had spread to otherFood and DruR .kdtnin- organs, so the results werein because it produced very impressive - the largestnt results in a trial of improvement in survival times with advanced bowel reported in a final-phase cIin-

cat study for any single addi-.he first of a new class of tional form of treatment.

shorm?n#sâw SW"

speed with which the FDA hasrSewed and approved Avas-tin is testimony to the ground-breaking scientific and medi-cal importance this treatmentbrings to cancer patients."

Roche, which holds a mOri-y stake in Genentech, will

market the drug in Europe.l'he company is looking at the

tiafl,enefitsolA)n

/

lest/be a 111efor thousands

THOUSANDS of lives could besaved each year with a ground-breaking test for major cancers.A simple and cheap measure of

hormones in the blood could Iden-Ii& pcople at higher risk otdevetop-ng the disease. ..

V

hestigation by John CornwellPDF compression, OCR, web optimization using a watermarked evaluation copy of CVISION PDFCompressor


liOns of people from dying of cancer andthimass killer finally about to be tamed?

AN BE WO\

4!

uru oU.tme to beOtJmes more effee-Current treatmentsinced by scientistsof the scattergunconventional drttgs, iturs like a bullet, saidavid Thurston of thet London's School of

nctrat work"e a bullet

could be available to patients withinthe nest five yazs.

Profesaor Thuraton said SJG-136worked Qy attactnflseltto the DNAof cancer cells, preventing them rtomrepmduckngBtlt., unlike conventionItreatments, where norm*l cells areftkso dritroyed the drug left, thehealthy eeils alone, he added.'Current nhemothera y drugs

the

wcwtwx Sxccc,\\cwlva% tctea. t

A NEW drug which shrinksbreast cancer tunIottrs couldsave thousnna at' womenfrom the devastating loss of abi'east,Arin)tde reduces the lump In

sIfle so it tan be removed withoutI-he need fkr a Iflssteetomy' oneof the R test tears rot' womendisenosedI With the disease

It also wo0-.tor tt'(2IIten or.tkw.,y'--.:: $91!4. 11*

netuded 6(10 Sritish women, showedfear of IOSIIIB a bi'eafl Was OflO oftheir moat vommon Concerns andone' third wanted treatment thatwould allow then. to kc-rp It.

ftpsillt8 from two si utlies tdons.ccl yesterday at tile 4th l(uropenui-east Cancer Conkrrnco In 11am.burg .- thow that In lu,lf of wonion

ev I g ArimIc*.x, I-halt I motifs

ritain wiJi hep to test the long-tereffects of a drug that could revolultreatment reports

,-\ \.-\CC'lNr It' Ii'_'aI :\tistrstiail hioltt'hfloncIoflonu Iii IkI IItkS I or PIfl)' CSL. Ii%ki,1 CSIIOI ------IC) IA' te4ied toO. spocifle to thcin ri sill tfivr ui ,cour in caIiØ the N I-E50' I



2

rlando ConventionCenter. Florida: something big was about tohappen. Excitement at the world's biggest annualcancer conference last month was palpable. Eightthousand specialists had crowded into the mainauditorium for an unscheduled announcenieng4,000 more spilt into adjacent hails where theycould watch on TV monitors.

On the podium was Professor George Sledge,the chairman of the education committee of theAmerican Society of Clinical Oncology(Asco, widely regarded as the world's leadingspokesperson for the science of cancerHe had summoned the delegates to announcethat a drug called Herceptin had achieved adramatic reduction in breast-cancer deaths.The results were part ofan international studycalled Hera, involving 5,000 women.

The study began in 2001 and is being conductedin 39 countries, including Britain. Hercepein,Sledge said, had achieved a 46% reduction in therisk of recurrence of the early stage of' anaggressive breast cancer affecting 25% ofwomen. Recent trials have shown similar resultsin women with an advanced stage of thecondition. He continued: "These are the moststunning results in a clinical trial in my entireprofessional career." The findings, he vent, were"astonishing beyond belief Biology has spoken,we should listen.., a new age now begins".

After the figures were read out by the Belgianlead investigator. Dr Martine Piccart. there was afive-minute standing ovation. The significance isindeed stunning. Nearly 10% ofwomen willdevelop breast cancer during their lifetimes. Eachyear, more than a million new cases arediagnosed worldwide, with a death rate ofnearly400,000 per year. In Britain, breast cancer is thecommonest cancer, though it is rare in men.Over 100 new cases are diagnosed each day. Itremains the third commonest cause ofcancerdeath, with around 13,000 victims each year. TheHera result suggests that the lives of2,800women could be saved each year by Herceptin.

The Orlando audience, hype-tigued byyears ofpromises ofmagic-bullet cures in thepipeline, was powerflully convinced. Each cancerspecialist worthy of the name knows that thescience behind Herceptin is being applied inlaboratories around the world in the hope oftransforming treatment notjust ofbreast cancerbut also ofcancers of the lung, prostate, stomachand ovary and leukaemia.

The strategy in scientific terms, is to identifymolecular targets for cancer therapy. Hercepein,like another leading cancer drug Glivec, isdesigned to activate or deactivate exquisitelycomplex molecular interactions in the body

'We can tamecancerin the sameway thatwe tamed Aidsin the FirstWorld byfocusing.science andfunding at it'

he new scanners andrugs that couldave millions of lives

Left: aCT scanof a cancerouslung tumour,PetetT scanners(above andright) show

eater detail.

creating an entire new group of cancertreatments. Herceptin works by interfering withone of the ways in which cancer cells divide andgrow Givec, used to treat chronic myeloidleukaemia and a rare stomach cancer, works byblocking signals within cancer cells andpreventing a series of chemical reactions thatcause the cells to grow and divide. LikeHerceptin, it could work for other types ofcancer, including cancer of the prostate.

This year's Asco meeting attracted a record25,000 cancer experts, filling up the hotels ofOrlando which normally play host to DisneyWorld tourists. They had jetted in from all partsof the world to meet and greet collaborators whonormally correspond by e-mail. Year after yearthey have been returning to their clinics andlaboratories increasingly daunted by theever-expanding evidence of cancer's hideouscomplexities. But this year was differentWe were wimessing, I heard more than onedelegate say "a paradigm shift", the phrase firstemployed by the philosopher Thomas Kuhn todescribe how science progresses by longperiods ofstability punctuated by a revolution,after which nothing is the same again.



These two set

scans revealthe liver, hateafter cbemottThe cancer w

detected usiAscanning, whiblends twocomplementacancerimagiimethods intoone scan.

Figures 1are theCT scans,

figures 2are the Fe

scans, a

sof flgures3a .ancer of CT and Pet scans. It isre and these fused Images'erapy. (figures 31 that giveis the most completeg Pet/CT information on cancerch location and

metabolism. Inset:ry .. Herceptin, therig drug that could

: eliminate theneed for

chemotherapyandradiotherapy If

cancer isdetected at

Q!aII7 stage

orig the optimists was Professor Ian Smith,der of the British group in the Hen study and

ead ofthe breast-cancer umt at the Royallarsden hospital at Chelsea and Sutton. Akeerful man with a riotous thatch ofgreyingñy hair, he has an inside track on the Heraults. He said that HEGF (human epidermal

bwth factor) is a protein that occurs naturallythe body Sometimes it attaches itseWtoother protein (Her2) on the surface of breast-ncer cells.When this happens it makes the cellsSc and grow. Herceptin, developed in theboratories of the pharmaceutical companyenentech. blocks this process by attaching itselfithe Her2 protein so that the epidermal growthrtor cannot reach the breast-cancer cells. Thisops the cells from dividing and growing The)mpound also stimulates the body's ownunune cells to help destroy the cancer cells.'hatwe need to do," says Smith, 'are specialtibody tests of all breast-cancer patients atagnosis to determine everyone who couldnefit from such treatment."Behind the Herceptin story are developmentsmedical science that have been a long timeming. As Dr Charles Sawyers ofthejonsson

Comprehensive Cancer Center in LA told asession at Orlando, it had taken 40 years, fromthe earliest work on a single chromosome(a structure within any cell containing DNA,encoding genetic information inherited fromonc's parents), to bring compounds likeGlivec and Herceptin to the clinic. Theinterveningyears had seen advances in the studyofpure biology at the microscopic level inparallel with advances in genetics. The $3 billionhuman genome project (which identified thesequence of all the genes in the humanorganism) was completed in 2001. The task oflinking these genes to the risk of cancer isongoing but hugely complex and problematic.Ofthe 30,000 genes revealed in the project,many are novel with no resemblance to agene of known function.

One of the biggest tasks facing biologists is topredict the 3-D structure of the proteins thatarise from DNA instructions. It has not beenplain sailing. The theory behind antibodytherapy for example, looked straightfoard atthe outset. Our natural antibodies are the firstline of defence against invading antigens orinfections. Our immune system is composed of a

vast library of these antibodies vhich areattracted to the invaders: each antibody grasps aspecific target while alerting the rest of thesystem to the nature of the intruder. The idea isto design appropriate antibodies preciselyto target antigens produced by tumours, and toinject them into the bloodstream to do battle.

The long progress to new rationalised drugsfor cancer, such as Herceptin, Glivec, Erbitux (forcolon and rectum) and Ritux (for non-Hodgkin'slymphorna) contrasts dramatically with the wayin which chemotherapy was discovered.Chemotherapy, a cytotoxic (meaning that it killscells), is the traditional treatment ofchoice tocombat the spread ofcancer. It was discovered asan unsuspected side effect ofmustard-gasweapons on people who happened to besuffering from cancer ofthe lymph nodes. Ensome cases, a gas dose, which normally causedblindness and imploding lungs, temporarilydestroyed the cancer. it became the basis ofvariations ofcheniotherapies that tend to killcancerous cells, and destroy healthy ones too,while damaging the immune system in theprocess. The side effects are the fear of all cancersufferers: nausea, hair loss, skin afflictions. )))± 23



Today chemotherapy is more sophisticated andaccurate in targeting cancer cells, but too oftenthe more aggressive cells hibernate and returnwith a vengeance. Most scientists workingwith the new inhibitors and monoclonalantibody treatments acknowledge they will beused in combination with chemotherapy foryears yet. The art is to get the combinations right.

Another speaker at Orlando was ProfessorPaul Workman, a biochemist by training whodirects the Institute of Cancer Research atSutton. He has 170 scientists working with him,an army of geneticists, molecular biologists andbjochermsts. He works in conjunction with unitslike the Sanger Institute in Cambridge, andcollaborates with leading drug companies. Hetells me in a reassuring buttered-toast Cumbrianaccent: "This is an extraordinary time in thisfield. We're approaching a point, in five or sixyears time, when cancer will become a chronicdisease Eke diabetes or high blood pressure."

We've heard this sort of thing before: fromPaul Workman himself but mainly in the formofpromissory notes from the pharmaceuticalindustry which is spending up to £4 billion ayear in research and developmenton biologicalstrategies for cancer and which bombardsinvestors with good-news blandishments. So is itfinally true? And what does it mean for cancer tobecome a chronic rather than a killer disease?

The significance of what happened inOrlando last month - ifProfessor Sledge's claimsstand up - goes to the heart of that overworkedphrase,"paradigm shift". Is our understanding ofcancer about to be revolutionised from the labbench right through to the hospital ward and theclinic? In the case of Herceptin and itscompanion drugs, there is now evidence ofsignificant clinical change even before the drugscome on stream, ofwhich more later.But thecultural and psychological consequences inprospect arejust as profound, ifnot more so.

They amount to a dramatic shift in our notionof why we have cancer, how we experience it,socially and psychologically, and the prospects forsurvival. We all know about smoking unwisesunbathing alcoholism, lack of exercise and poordiet. But down the years, the causes of cancerhave included cultural, social, and even moralperspectives. W H Auden proclaimed in ahideous poem tided Miss Gee that sexualrepression can be the culprit. Norman Mailercited America's moral decay- "cancer gulch'The late Ted Hughes insisted that his bowelcancer resulted from a failure to stick to poetry, asifhe had failed to rake his broccoli. Hence cancercan be your own fault, even ifyou've neversmoked or had a drink in your life. Cancer'smalignancy a curse that invariably ifnotinevitably ends in death, infects the way patientsare regarded, and how they regard themselves.

Lastyear, Kate Carr,a formercolleague on thismagazine, died of breast cancer. Her book abouther illness, It's Not Like That, Actually waspublished posthumously In the seventh year ofher survival she wrote: "I am a cancer survivor, a

survivor of the disease, but also a survivor of theshed loads ofabsolute rubbish that is talkedabout cancer which has made myjourney harderthan it needed to be:' Her hook is comparable inharrowing power to Susan Sontag's Illness asMetaphor and Aids as Its Metaphors, whichtnsists that cancer is too appalling to invite idlehypotheses of any description. Cancer is also tooserious for loose talk about science "winning thecancer war'ç unless it is absolutely true.

Most cancer scientists admit that the war willnever be won. But if cancer becomes "chronic"itwill go a long way towards dispelling its uniquelymalignant reputation, along with its consequentterror and stina, which are as much a part of thesuffering as the pain and fear ofdeath. And thecancer specialists had better be right, for there is,as Kate Carr eloquently argued, too much atstake for more flilse promises. And if there is tobe a new class ofdrugs arid associated tests thatmean the transformation of cancer front masskiller to routine chronic disease, we must askwhether the new treatments will be available forall, and for every kind of cancer.

Arresting the disease, and improving thepercentage survival rates beyond five years, then10 years, is crucial to claims about thetransformation of cancer to "chronic" status.Survival rates vary greatly between differentforms ofcancer. For example, 3% of suffererswith rare cancer of thepancreas survive beyondfive years; and 13% of sufferers with stomachcancer survive beyond five years- whereassufferers ofcancer of the testis have a 95%survival rate. The hope is that the survival rate ofbreast-cancer sufferers (currently 77%) will riseto match that of cancer of the testis.* * * * *So what is so different about the effect ofHerceptin and similar drugs?How can theytransform cancer into chronic illness? The natureof'hronic" as opposed to imminently life-threatening can be seen clearly in the case ofprostate cancer, which mainlyoccurs in agedmen (most men over 80 have a slow or dormantform of the disease). Doctors talk of such cancersas being either pussycats or aggressive andinvasive tigers. (In 2000, 27,000 men werediagnosed with prostate cancer, and 10,000 met'died of the disease. Survival rate beyond fiveyears was reckoned to be 65%.) The pussycat - amilder cancer svill linger without causingmuch trouble to a man, and he will probably dieof something else. his therefore "chronic". Thekey to the new drugs, combined with traditionalmethods, is to tame clinically as many aggressivecancers as possible. In psychological terms, forpatients, it's the difference between beingreleased from prison on a tagging system, andremaining on death row under threat ofsudden execution.

The paradigm shift to cancer as chronicdisease is already involving radicalchanges in theclinic. The traditional methods oftreatment arethe tripartite strategies known with mordantirony as "slash, burn and poison": surgery,

Thanks to better screening, the number of deathfrom cancer has decreased in the past 20 yearsLung cancer is the biggest killer in men and worn

HOW THE DISEDr Johanna Lohn on the 0115Charting the long-term stages of cancer has beencrucial to our understanding ofthe disease and howto treat it biologically as well as with surgery,radiotherapy and chemotherapy. Cancerof the howefor example - the fourth most common form of thecondition worldwide- is believed to result frommutations in genes that regulate bowel tissue. Formost people, these mutationsoccur spontaneously.A healthy bowel is lined with cells that have twofunctions. One is to produce mucin, which lubricateithe passage of the faeces; the other is to absorbwater, so the liquid faeces become more solid by thetime they reach the rectum. As the faeces movethrough the bowel, they rub away surface cells on thlining. To overcome this problem, the bowel surfacecontains well-like holes known as crypts. Cells at thebottom of the crypt divide to replace the cells lostfrom the surface. As they form, they after to becomemucin-producing cells or water-absorbingcells. The:do this by receiving signals from the tissue on whichthey are sitting, which tells them about their locatioias they move up the crypt. The signals are receivedreceptors, rather like television aerials, which existon the surface of the cell.

If one of the genes sends messages that disruptthe regulation of the cells in the crypt, they canbecome faulty, affecting the entire crypt. The cryptstill a long way from being cancerous, but one of itscells might develop another fauft, perhaps in one of



Cancer incideuc sand deathCombined men and wUmi

ToplO cancers for sampley

1998

The 10 biggest killeWorn

M1985 U1994 12003

I

GETS A GRIPA

nvel cancerenes controlling cell division. As well as the cells

ling chaotically at the bottom of the crypt, theybegin to divide right up the side and onto the

ace of the bowel, where they bubble up to form a

p. This is not yet a cancer, as the cells are still

ing the rules of territory. Cell biologists, working

laboratory with mice, have managed to switch

gene known as APC so as to replicate this

ess of irregular cell division and its increasing

ations. They have observed the point when

rrnally dividing cells fail to die when they should

death is a crucial aspect of healthy normal

. And if one of these immortal cells in the polyp

jires another genetic fault with the capacity of

siveness, it will break out into other parts of thec This characteristic of aggressive invasiveness,

immortality, constitutes the deadly nature of

er proper. The cells begin to migrate through

pall of the bowel and out to the lymph nodes. if

ells get into the blood they travel into organs

he liver and lungs, and into the bones, clogging,

ierating and destroying the normal function ofody and becoming life-threatening.

this natural history of cancer, and a

ghtforward version of it, could take two or

decades to develop. How does it begin? There

long been epidemiological suggestions that

of fibre or excess of red meat in the diet is to

je. However, the expert jury is still out.

Professor Ian Smith

'We needto do. specialantibodytests on allbreast-cancerpatients tofind out whocould benefitfrom suchtreatmentj'

radiotherapy and chemotherapy Here is a typicaltreatment case, with a twist that illustrates thedistance measured from the traditional to thepromised new approach. Frances Wilrnot,a librarian who was operated on for appendicitisin 1998, at the age of4l, tells me: 'A youngregistrar came to see me after the op. She saidsomething unusu1 had turned up. I guessedwhat from the look on her &ce?' A malignanttumour was spotted on her inflamed appendix.

Frances was referred to Addenbrooke'shospital in Cambridge. After an ultrasound testand a physical examination, ovarian cancer wasdiagnosed She was operated on a week later'They found tumours as far down as the boweland up into my diaphragm," says Frances. "Theygot most ofit, but not all. Chemotherapy wasinevitable. I was in shock, but the worst was thelack ofinformation. I wanted to know how longI'd been suffering from the disease, but nobodywas prepared to even guess." She was also upsetby the lack of interest in the causes. Frances doesnot smoke or drink, had always been fit, atehealthily walked and danced regularly But theclinicians said, "We don't do causes."

The next month, December 1998, Francesbegan a four-month course of taxaterechemotherapy Before being discharged she wastold thai only 15% ofovarian-cancer patientswith her grade and stage of tumour survivebeyond five years. Having suMved nearly sevennow, she regards herself as fortunate. But she isnot complacent: "The fact that I have beaten theodds by two years doesn't mean i'm in the clear?'Frances has received no further treatment toprevent the return of the disease. Like most othercancer sufferers, she realises that there isno cure. But in the seven years since shecontracted her cancer, clinicians at hospitals likeAddenbrooke's no longer say: 'We dont do

causes?' Causes - involving genetics, molecularbiology familial and a host ofenvironnientalfactors - are moving from the science labs andstatisticians' computers into the wards.

One in three people in the industrialised Westwill contract a form of cancer in their lifetime.About 7.8m new cases were officially diagnosedworldwide in 1990. This year the figurestands at 1 Om. Owing to increased longevityenvironmental factors, sophisticated diagnosisand registration procedures, that figure is set todouble by 2020. Worldwide, according to newfigures published by Cancer Research UK,breast and lung cancer have doubled since 1975.

According to the latest statistics, althoughdeaths from cancer have decreased in the past 10years, the disease is responsible for a quarter of alldeaths in Britain. In 2002 it claimed the lives of155,180 people. Lung cancer accounted for thelargest number ofdeaths, at 33,602; then bowelcancer, at 16,220. In men, 9,973 died ofprostatecancer. Despite the increasing incidence of thedisease, from 1993 to 2002 the gross mortalityrates for cancer fell by 13.5% for men and 9.8%for women. Mortality from breast cancer in theUK has fallen from 15,625 in 1989 to 12,838 in2002, indicating a 28% decrease. The reductionis due to several causes, including betterscreening, improved care, and the widespreadadoption oftamoxifen since 1992. But thesereductions hardly ment the claim that cancer isbecoming a "chronic" disease. It remains a masskiller that indiscriminately hits the young andthe old, the rich and the poor, the sickand the fit, in their many tens ofthousandsannually: So are these devastating realities aboutto change? Are the scientists about to deliver?

Professor Bruce Ponder, an athletic-lookingman in his sixties, is one of the contributors W* 25PDF compression, OCR, web optimization using a watermarked evaluation copy of CVISION PDFCompressor


to the discovery of the BRCAI and BRCA2breast-cancer genes. He heads the CambridgeOncology Centre, set to become one of thelargest cancer-research sites in Europe, with 500scientists. On his walls are plans for an array oflaboratories that will eventually interface withthe Sanger Institute for genetics and the cancerunit in Addenbrooke's hospital Ponder does notslip easily into hype or loose exaggeration: hetellsyou how it is. "Cancer," he says, "can nolonger be described in a linear step-by-stepfashion. We have come a long way in the pasttwo decades, and what we see is dauntinglycomplex. It's like walking on a waterbeth resolveone problem and five or six others pop upsomewhere else. It is not one disease, it'shundreds. There are a dozen or more differentkinds ofbreasc cancer alone."

A crucial dimension ofhis strategy has been tocreate a physical interface between the hospital

d the laboratories. "I have raised a budget ofS3m a yeai" he says, "to ensure the clinicianshave time to do the underlying science incollaboration with full-time researchers. We alsohave the opportunity to bring many disciplinesto bear on the study of cancer, includingmathematics, physics, chemistry engineermgcomputer science, statistics, pharmacology..

Tins multi-dimensional approach, with a viewto bringing a new focus on the disease andtreatments, will connect more directly and earlierwith the patients on the wards and in the clinics.When specialists like Ponder speak of a cancer's"natural history", they contrast it with the healthybody. Knowledge ofthe molecular biology of thehuman body in health has been expanding for20 years. So has our knowledge of cancer. Thegrowth of a cancer has a different path ofdevelopment from that of the healthy body It isan alien accumulation of cells that lies low,mutating again and again, often without obvioussymptoms and before spreading out and seizingits prey the healthy cells and organs ofour bodies.

"A defining characteristic of cancer is its slowpace of development," says Ponder. "Studies ofthe link between lung cancer and the increase ofsmoking in women, for example, reveal a lag ofthree decades between an increase in the habitand a marked rise in lung cancer. This time spanreflects the accumulation ofmultiple biologicaland genetic events, maybe seven or eightinterrelated occurrences over a period of years?'

As he says this, I have the impression of fail-safe devices going wrong in an aircraft. Manygenetic mechanisms, lie says, have to go wrong,severally and together, before the system beginsto faiL "Cancers are commoner in old people,"says Ponder, "not so much because they're moresusceptible, but because there is a time lag in theoccurrence ofa set of abnormal events in cellssufficient to cause damage to the DNA - theinstructions that regulate normal organisation ofcells and tissues?'

Traditional choices ofcancer treatment havebeen between localised therapy, designed toremove a tumour at the site where it has appeared,

such as the bowel or breasq and systemic therapy,combating the spread throughout the body.Local treatment - surgery or radiotherapy - isappropriate where the cancer is confined to aparticular organ or area. Systemic treatment -chemotherapy - is used when the cancer hasspread. When deciding on traditional therapy,cancer specialists have taken two perspectivesinto accoune "the stage'; meaning how far thecancer has progressed from localised to invasivecancex-, and "the grade", meaning the degree ofaggressiveness of the cancer. The grading processhelps the specialist calculate the likelihood ofspread. "You may not be able to see the spread,because the effects are too small; but you can tellfrom the grading ofthe primary tumour as to thelikelihood that it has done so," says Ponder. "Inthis case you'd treat the patient as ifthe spreadhad occurred, as a kind ofinsurance policy?'

At the same time, specialists devising strategiesfor screening, treating and preventing cancerhave considered influential factors. There arc

ProfessorPaul Workman

'It is an extraordinarytime. In five or sixyearsCancer will becomea chronic disease, likehigh blood pressure'

well-known external influences that can reduceincidence: such as givtng up smoking avoidingultraviolet light, and screening for certain viruses.Then there are internal factors, such as the actionofhormones, like oestrogen and androgen, thataffect the speed with which mutated cellsdevelop further abnormality. The femalereproductive hormone oestrogen, for example, isa driver of breast cancer, and tamoxifen isprescribed to lower its action. A driver forprostate cancer is androgen. which can also bereduced by drugs.

Another factor involves a tendency for healthycells to assist the growth of cancer cells. Forexample, blood vessels sometimes form at thesite ofa tumour to stimulate the growth of theirregular cells that are sending out signals fornutrients to aid their proliferation. At the sametime, increased knowledge ofan inheritedsusceptibility - identifiable genes for particularcancers - has enabled scientists to identify "atrisk" groups ofthe population. In the case of thegene for thyroid cancer, clinicians recommendremoval of the thyroid before it causes trouble.

The standard surgery and radiotherapytreatments have remained unchanged in recentyears. but there have been continuedimprovements in the basic strategies. Walkingthrough a cancer unit like the Royal Marsden inChelsea and at Sutton, one sees evidence of

remarkable new lot. A new generation CT-Petscanner, working in 3-D and colour-coded,allows specialists to locate rumours for surgeryand radiotherapy as well as assess the benefits ofchemotherapy. An advanced surgical robot cannow be used for delicate tumour operations.The surgeon sits at a console and operates therobot by remote control. In prostatectomyoperations, to combat early cancer of theprostate, the machine can reduce patient time inhospital from a week to two days, anddramatically reduce blood loss from a litre to acouple ofhundred milhlitres. It also avoidsdamaging nerves around the prostate, reducingthe risk ofincontinence and impotence.

A huge problem with radiotherapy has beenaccurately targeting the dose when the tumourhas spread beyond the confines of surgery. Thispresents great difficulties, because every woman'sbreast is a different 3-D shape; it is important notto over-treat, and equally crucial not to under-treat. Radiotherapists have adapted a scanner that

targets doses on individual breast shapes withexquisite accuracy Another advance in surgery isa tiny microwave probe designed in Britain bythe company Microsulis. It works on theprinciple of heating cancer cells to a certain levelwhere they die, leaving healthy cells unaffected.

However, none of the improvements intechnolog or the refinements in cytotoxicchemotherapeutic drugs, have brought thedisease to a state that could be described aschronic: meaning an incurable disease that can bemanaged by medication, with a reasonable hopeof survival through a natural life span.

The key to that new hope is to be seen in anew unit known as the Oak Ward at the RoyalMarsden's Sutton branch, which opened earlierthis year. The atmosphere of the unit combinesthe comforts of a bright hotel lobby with aregular ward, but without the bustle and noise.There is a smart reception area, with a room forday patients, bays for hospital beds, an isolationunit, and a hospice area for long-stay patients.The Oak Ward is designed to be a hospital ward,just like any other, but it is also the focus ofEurope's largest cancer-drug developmentcentre. It enables 200 cancer patients, sufferingfrom every form of the disease, to take part intrials ofbiological treatments like Herceptinwhile being resident, or an outpatient, in a))),') 27



hospital setting. It could be the model ofspecialised cancer units for the future. For thecompledtv of cancer and its resistance to a cureindicate there will never be a time when yourdoctor will give you a simple test for the diseaseand write out a single magic-bullet prescription.

Professor Stan Kaye, the head ofthe unit, is acal].. besuited man with a calm consultant'sbedside manner. He does not talk cure.s but isconvinced that rationalised drugs produced inclose proximity to patients in trials are the wayfonvard. 'We are well ahead ofany similar sites inthe US, like tile Sloan-Kettering" he says. "Ourfocus is on discovering drugs that control thedisease, help increase life expectancy, minimiseside effects and maximise the quality of life.Some of the trials involve completely newagents; others involve known cancer drugs beingtested in combination with new compounds."

Then he conies to the nub of the newdesigner-drug strategy. "We're doing a lot ofwork with molecular-targeted chemicals that areselected to act on specific cancer cell signals tohalt their growth. We're also addressing the issueof drug resistance when a patient no longerresponds to treatment."

The good news is that the strategy thatproduced Herceptin, and is being tested on arange of drugs and types of cancers, appears to beworking. But there is also cause for concern.Constantly popping in and out of the ward are

top clinicians who are also scientists in their ownright. DrJohan de Bono, a stocky man ofMaltesebirth with a Glaswegian accent, buttonholed meon his own speciality: prostate cancer. He has 20compounds lined up to put into trials, butreminds rue that bringing a drug to marketnowadays, given the hoops that pharmaceuticalcompanies mustjump through, can cost up to£500m. He adds that of every 100 drugs on thedrawing board, only one tends to make it tomarket. De Bono also makes another tellingcomment "We can tame cancer the same way wetamed Aids in the first world with anti-rerroviraltreatments, by focusing science and funding at it."

Another consultant, Professor Andy Pearson,who heads the children's cancer unit at the RoyalMarsden, is as enthusiastic as his colleagues aboutdevelopments. But he warns of a danger de Bonohas raised by implication. "We have a situation,"he tells me, '\vhere some 75% ofchildren'scancers are cured by traditional methods. Youzap the cells and they tend not to come backbecause of the youth of the patient. This meansthere may not be the commercial incentive toput drugs through the massive developmentcosts necessary for the remaining 25%, as there isno prospect afa decent return."

The problem, well known in the realm ofpharmaceutical development, is that of"orphandrugs", which can only be solved by thegenerosity of charities, big pharmaceutical

companies, and governments. By the same tokeas with expensive retroviral medicines, there isadanger that the benefits of new cancertreatments will be concentrated in prosperouscountries and comrnunities,just as First Worldcancers begin to expand in the Third World. It isno secret that the tobacco industry has begun toconcentrate its marketing into Africa (givingaway free cigarettes to the young), where thestnoking habit has not yet taken offand lungcancer is still virtually unknown.

Dc Bono and Pearson have also raised crucialquestions about the fate of patients who have notbeen lucky enough to get into trials at sites suchas the Royal Marsden. The links between thelarger teaching hospitals that specialise in cancertreatment, and oncology units like the RoyalMarsclen are constantly improving andconiputerised exchange ofinforinadon shouldmake scientific expertise widely accessible at adistance. But there are doubts as to whether thebenefit ofdrugs like Herceptin will be availableto the wider population of breast-cancer patientsWhile there are tests available at a cost ofL5O toestablish if a breast tumour shows Her2 positive,only 33% ofwomen are being offered them.According to the pharmaceutical companyRoche, nearly one-quarter ofbreast-cancersufferers die without ever having had a Her2 testconducted. Some centres work on the mistakenPDF compression, OCR, web optimization using a watermarked evaluation copy of CVISION PDFCompressor


'C

fessordy Pearson

'There may nOt be thecommercial incentiveto put drugs through themassive developmentcosts necessary'

imption that it would be less costly to waitila patient progresses to metastatic disease tolertake the test. Herceptin will be available atnce for all patients early next year. but someti-es may wait for a decision from theeminent medicine expenditure regnlator;e (National Institute for Clinical Excellence).C19,500 per year, it is expensive, and ifNiceows its current timescale, a decision may notEorthcoming until 2009.or Dr Martine Piccart, a lead investigator ofworldwide Hera study on Herceptin, thereno ifs or buts. "In advanced breast cancer," sheI in Orlando, "Herceptin has demonstratednt prolongs patients' lives. To see suchressive results with Herceptin in early-stageast cancer... is a major breakthrough in the

treatment ofthis aggressive disease." She went onto say that every woman who had breast cancershould be tested to see ifshewas I-Ier2 positive,and if so, she should have Herceptin after surgeryand with other chemotherapy.

For a breast-cancer sufferer, the issue ofHerceptin is emphatically one of: can I get thetest? and will T get the drug?Jill Askam is a43-year-old former executive in the clothingindustry. She discovered a swelling under herarmpit in October 2002 and was diagnosed withan aggressive breast cancet Throughout hertreatment she insisted on "taking charge", asmuch as she could, ofdecisions about hertreatment. She studied the latest developments01) the internet and was not afraid to ask for whatshe wanted. She insisted on being referred to the

Royal Marsden in preference to her GP's firsthospital choice, and consequently had hermastectomy a month earlier. She asked to go onthe Hera trial, and when she was told that hertumour was not Her2 positive (having been toldoriginally that it was), she insisted on having thetest again. It came back positive (part of thetumour proved positive, part neganve and shesqueezed into the Hera trial days before it closed.She was chosen by random selection to take thedrug rather thanjoin the observation group.

After a year on Herceptin,Jill tells me she feelswell, and confident "The confidence comesfrom knowing that treatments like Herceptin areworking for many women with aggressive breastcancers. So it also comes from knowing that I'vehad the best that's available."

Jill's confidence sounds more like someonedealing and managing a chronic illness, ratherthan a patient "fighting" against the odds. Not allwomen have her determination, however, andthere was a large measure of luck in her beingaccepted on a trial.

For no the good news from Orlando seemsdestined to give confidence to cancer sufferers ata future date rather than today Transformingcancer into a chronic disease isjust a promise forthe majotir); but it's a realistic one. Meanwhile, ifHerceptin is only half as good as the trialssuggest, it should be available, like the Her2.test,for every woman for whom it brings benefit



featuring :teenage bombers against the …...featuring :teenage bombers against the russians, and...

Documents