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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