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Biomarkers for Colorectal Cancer
The National Biomarker Development Alliance
Forum
March 25, 2013
Raymond N. DuBois, M.D., Ph.D.
Executive Director
The Problem
Worldwide about 1 million people
develop colorectal cancer each year.
Of these, 50% will die of systemic
disease within 5 years of their
diagnosis.
450
350
Incidence
Per/100,000 250
150
50
30- 35- 40- 45- 50- 55- 60- 65- 70- 75- 80- 85+
34 39 44 49 54 59 64 69 74 79 84
Age
APC/Wnt
-catenin
Normal
Epithelium
Small
Adenoma
Kras
BRaf
Smad4 PI3K/ p53/
TGFRII PTEN Bax
Large
Adenoma
Cancer
Metastatic
spread
Biomarkers for detection of CRC
Impact of KRAS mutations on patients treated with
an EGFR antagonist
Therapy
Treatment response rate
KRAS mutation
positive
Median patient survival
KRAS mutation
negative
KRAS mutation
positive
KRAS mutation
negative
Metastatic CRC
Cetuximab
0/36 = 0%
34/78 = 44%
9 weeks (PFS)
32 weeks (PFS)
Panitumumab
0/84 = 0%
21/124 = 17%
7 weeks (PFS)
12 weeks (PFS)
Using biomarkers wisely has the potential
to save health care dollars
Assume there are
∼50,000 people per year
with metastatic CRC in the
USA.
The estimated cost savings
per patient in the
cetuximab-only strategy is
$8,040.
Using KRAS testing to
direct therapeutic
decisions would save over
$400 million per year