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PERSONALIZED CANCER CARE:
WHAT DOES IT MEAN?
THE ASPIRATION TO BASE A TREATMENT ON THE UNIQUE
BIOLOGICAL FEATURES OF A PATIENT’S DISEASE THROUGH THE
IDENTIFICATION OF VALIDATED BIOMARKERS OF
RESPONSE/RESISTANCE TO THERAPY
AIMS
TO IMPROVE DRUG EFFICACY
TO AVOID INAPPROPRIATE DRUG EXPOSURE (PRIMARY RESISTANT TUMORS)
TO MAXIMIZE QUALITY OF LIFE
TO SPARE UNNECESSARY COSTS
THERAPEUTIC TARGETING OF THE HALLMARKS OF CANCER
Hanahan & Weinberg, Cell, 144:646, 2011
PRECISION MEDICINE IN ONCOLOGY
BIOMEDICAL
RESEARCH
Phenotype
ACCURATE
DIAGNOSIS
TARGETED
THERAPY
Genotype
NEW PARADIGM
OUTCOME
Clinical characteristics
GENETIC MUTATIONS IN
LUNG ADENOCARCINOMAS
13%
8%
EGFR
Infrequent
NF1
KRAS
NTRK
10%
20%
STK11
17%
BRAF
PIK3CA
4%
ERBB4
5%
EML4-ALK
Adapted from: Nature. 455: 1069–1075. 2008
ErbB2
4%
3%
5%
64
RESULTS ON 131 PATIENTS
Siena et al., JNCI 2009
MULTIPLE MOLECULAR ALTERATIONS EFFECT
ON RESPONSE TO anti-EGFR mAbs
Because of the occurrence of multiple molecular alterations within the same
tumor, we investigated a cohort of 131 patients treated with EGFR-targeted
moAbs in the chemorefractory setting by separating patients according to the
actual number of molecular abnormalities within the same tumor (i.e. none vs 1
vs ≥2 alterations) among KRAS, BRAF, PIK3CA mutations and loss of PTEN.
The probability of response was:
50.0% (22/44) among patients with no alterations,
4.2% (2/47) among patients with 1 alteration and
0% (0/23) for patients with ≥2 alterations,
0 (“
“quadruple negative”
”)
1
(p<0.0001
2+
number of molecular alterations
objective response rate
50%
5%
0%
Sartore-Bianchi A et al. PLoS One 2009