biología tumoral: una visión global del cáncer hoy
TRANSCRIPT
Prof. Jesus Garcia-Foncillas MD PhD
Director
Biología tumoral: una visión global del cáncer hoy
Very limited knowledge about Cancer without Molecular Biology
Not equal all breast cancer
Precision Oncology: A paradigmatic change
Towards new screening approaches
Human Plasma Proteome
Molecular cancer screening
Molecular cancer screening
Clinical Oncology: A paradigmatic change
Classical cancer diagnosis is not enough
Birt-Hogg-Dubé: BHD(FLCN)
Different types of renal cancer
Clinical Oncology: A paradigmatic change
Molecular assessment: predictive & prognostic
Phase III PRIME study
Ras assessment
Douillard J-Y, et al. N Engl J Med 2013;369:1023–1034
12 24 36 48 60 72 0
25.8
20.2
Prop
ortio
n al
ive
(%)
0
20
40
60
80
100
HR 0.77 (0.64–0.94)
p=0.009
Months
Panitumumab + FOLFOX4 (n=259) FOLFOX4 (n=253)
Ras assessment
Van Cutsem E, et al. J Clin Oncol 2015;33:692–700
Cetuximab + FOLFIRI (n=178) FOLFIRI (n=189)
Months
Ove
rall
surv
ival
(pro
babi
lity)
54 42 48 18 0 6 12 24 30 36
28.4
20.2
0.0
0.2
0.4
0.6
0.8
1.0
Phase III CRYSTAL study
HR 0.69 (0.54–0.88) p=0.0024
PFS
B-raf meta-analysis
OS
B-raf meta-analysis
Oncotype DX Colon Cancer Assay
12-Gene Oncotype DX Colon Cancer Assay: 7 Recurrence Genes + 5 Reference Genes
48 Genes with
Significant Impact on Recurrence
3 NSABP Studies:
1,086 Patients
Cleveland Clinic:
765 Patients
O’Connell et al. J Clin Oncol. 2010.
761 Genes
Assessed
Oncotype DX Colon Cancer Assay
O’Connell et al. J Clin Oncol. 2010.
CELL CYCLE Ki-67 cMYC
MYBL2
ATP5E GPX1 PGK1 UBB
VDAC2
GADD45B
7 Recurrence Score Genes
STROMAL FAP
INHBA BGN
Recurrence Score result = 0.15 × stromal group − 0.30 × cell cycle group + 0.15 × GADD45B
5 Reference Genes
Molecular Biology is much more than Genomics
Moran S et al. Epigenetic Profiling to Classify Cancer of Unknown Primary: a multicenter, retrospective analysis. The Lancet Oncology 2016. Published online August 26, 2016
Many different clones
Ancestral clone
• Current approach in cancer requires a global perspective of all molecular mechanisms involved
• Liquid biopsy is the key for implementing the paradigm of Precision Medicine
• Editing genome based on CRISPR/cas9 is the next step based on a whole-genome data