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Brussels - European Parliament, February 18 th - 2014. How uniform is cancer care in Europe ?. Towards Personalised Therapies. Marco A. Pierotti Fondazione IRCCS Istituto Nazionale dei Tumori - Milan OECI Past President. MOLECULAR MECHANISMS OF CANCER :

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How uniform is cancer care in Europe ?

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Brussels - European Parliament, February 18th - 2014

How uniform is cancer care in Europe?

Towards Personalised Therapies

Marco A. Pierotti

Fondazione IRCCS IstitutoNazionaledei Tumori - Milan

OECI Past President


MOLECULAR MECHANISMS OF CANCER:

THE BEGINNING OF A NEW ERA

Cancer genetics

Multiple-stepprocess

APC

Hyper-

Methylation

APC

KRas

DCC

TP53

April 2003


TOWARDS P4 MEDICINE

PREDICTIVE

PREVENTIVE

PERSONALIZED

PARTICIPATORY

(David J. Galas and Leroy Hood)


to provide the right drug

to the right person

at the right dose

THE GOAL OF P4 MEDICINE


THE NEW SCENARIO

High-throughputtools

Molecularcharacterizationoftumors

Molecularclassification


MOLECULAR TAXONOMY OF BREAST CANCER

ER-

ER+

  • Association of discovered classes with survival and other clinical variables (Sørlie, PNAS 2001)

Class sub-type discovery (Perou, Nature 2001)

Validation of findings assigning class labels defined from class discovery to independent data sets (Sørlie, PNAS 2003)


MOLECULAR DIAGNOSTIC

Severalpathways are deregulated in humancancer

p-Akt, 42%

PTEN, 15%–41%

HER2, 30%–36%

PI3-K, 18%–26%

EGFR, 6%

EGFR, 32%–60%

p-Akt, 23%–50%

Ras, 30%

PTEN, 24%

HER2, 5%

PI3-K, 4%

Breast

Lung

TSC1/TSC2

IGF-1/IGF-1R

VHL

NET

TGFa/TGFb1, 60%–100%

VHL, 30%–50%

IGF-1/IGF-IR, 39%-69%

p-Akt, 38%

PTEN, 31%

TSC1/TSC2

Ras, 50%

p-Akt, 46%

PTEN, 35%

PI3-K, 20%–32%

EGFR, 8%

HER2, 3%

Kidney

Colon


THE NEW SCENARIO

Discovery of the molecular basis of cancer

Switch from the concept of cancer drug as a cytotoxic compound

to the knowledge based targetedtherapy


THE NEW SCENARIO

High-throughputtools

Molecularcharacterization of tumors

Molecularclassification

Targetedtherapy


IMATINIB/GLEEVEC AS A PARADIGM

FOR TARGETING KINASES

BCR/ABL inhibitors and CML therapy


Targeted Therapies: some numbers

Targeted cancer therapies

SaurabhAggarwal

Nature Reviews Drug Discovery 9, 427-428 (June 2010)


Targeted Therapies: some numbers

OncKive The Rising Cost of Cancer Care in the Era of Individualized Therapy: A Q&A With Thomas J. Smith, MD Anna Azvolinsky, PhD May 2012


The goal of targeted therapies:

To chronicise cancer

BUT

Genetic instability

≠ diabetes

or cardio vascular conditions

RESISTANCE


Ultimate goal

  • From chronicization

  • to eradication

  • with

  • combinatorial targeted therapies

  • and

  • macro/micro environment modifications


THANK YOU!

Marco A. Pierotti

Fondazione IRCCS IstitutoNazionaledei Tumori - Milan

OECI Past President


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