Official Opening9 October 2014

Graham MannCentre for Cancer ResearchWestmead Institute for Medical Research

Melanoma Institute Australia

Cancer: what we know… and what we don’t

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Cancer – the big picture (Australia 2011)

• 119,000 people newly diagnosed each year

• 43,000 deaths• burden >$100b

Commonest:• Women: breast, bowel,

melanoma, lung• Men: prostate, bowel,

melanoma, lung

Australian Melanoma Statistics and Trends

1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 20150

2

4

6

8

10

12

Age-standardised incidence (to 2011) and mortality (to 2012) rates by year

M. inc.

F. inc.

M. mort.

F. mort.

Year

Age-

stan

dard

ised

rate

Source: Australian Institute of Health and Welfare

Source: Australian Institute of Health and Welfare

Australian Institute of Health and Welfare (AIHW) 2015. Australian Cancer Incidence and Mortality (ACIM) books: Melanoma. Canberra.

• 3rd most common cancer in men and women, 4th overall• commonest cancer in younger adults

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What is cancer?• A group of related cells that is

growing and multiplying, if …• some of them never stop• and some can move elsewhere

in the body

They are our own cells, malfunctioning• growing when they should

have stopped• living longer than they are

supposed to• moving out of the places

where they belong

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How?All these normal functions are controlled in cells by genes, e.g.• cell multiplication genes • lifespan and cell death genes• genes that keep a cell where it

should be

• we have about 20,000 genes

They are our own cells, malfunctioning• growing when they should

have stopped• living longer than they are

allowed to• moving from the places

where they belong

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What causes cancer?All these normal functions are controlled in cells by genes e.g.• cell multiplication genes • lifespan and cell death genes• genes that keep a cell where it

should be

Cancer is caused by things that damage (mutate) genes (DNA)• some chemicals• some kinds of radiation• some infections• wear and tear (oxygen)

M. Lawrence 1st Annual TCGA Scientific Symposium, 2011

Australian Melanoma Statistics and Trends

1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 20150

2

4

6

8

10

12

Age-standardised incidence (to 2011) and mortality (to 2012) rates by year

M. inc.

F. inc.

M. mort.

F. mort.

Year

Age-

stan

dard

ised

rate

Source: Australian Institute of Health and Welfare

Source: Australian Institute of Health and Welfare

Australian Institute of Health and Welfare (AIHW) 2015. Australian Cancer Incidence and Mortality (ACIM) books: Melanoma. Canberra.

• 3rd most common cancer in men and women, 4th overall• commonest cancer in younger adults

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Why me?• Unlucky• Ageing• Exposed to more DNA damage, or DNA

damage to a particular site• (Rarely) a strong inherited predisposition

to cancer• (Commonly) a genetic background that

raises the odds

Bishop et al. Nature Genetics 2011

Common genetic riskDNA markers found more often in people with melanoma

MC1R

ATMCASP8

TYR

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… different tumours of the same type

M. Lawrence 1st Annual TCGA Scientific Symposium, 2011

International Cancer Genome Consortium(ICGC)

Nature. 2010 Apr 15;464(7291):993-8

Original goal: sequence 500 tumours from 50 different cancer typesInternational Cancer Genome Consortium

The Cancer Genome Atlas Network. Cell 2015

Diversity and commonality in 311 melanomas

The Cancer Genome Atlas Network. Cell 2015

Genes, pathways, targets

The Cancer Genome Atlas Network. Cell (in press)

Immune response

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What works?PREVENTION – but there are limits• new hope: individualised

EARLY DETECTION• new hope: target screening by risk

DESTRUCTION, if you can get it all• Surgery – newer, better• Radiotherapy – newer, better

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What works?

NEW FRONTIERS• Drugs that target the specific

mutations driving the tumour: ”personalised therapy”

• Overcoming the way tumours hide from the immune system

• They work!

PLX4720 co-Structure with kinase domain of BRAFV600E (Tsai J et al. 2008 PNAS)

New generation of kinase inhibitors w specificity for oncogenic BRAF (V600E)

from cancer genomics “1.0” 2002

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Why isn’t it fixed yet?Getting there …• it is fixed for some• we understand what works and

(mostly) why things fail• the end is in sightBut …• our system can fall short• more targets = more drugs• early days for immune therapy

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Thanks and questions

Casey Dunlop CRUKscienceblog.cancerresearchuk.org

Bernie Stewart IARCThe Conversation