LWBK1006-20 LWW-Govindan-Review December 12, 2011 19:4
Chapter 20•Cancer of the Gastrointestinal Tract 251FOLFIRINOX compared to single-agent gemcitabine alone. Therefore,
FOLFIRINOX should be considered for first-line treatment in patient
with good performance status and normal serum bilirubin level. FOL-
FOX has shown activity in patients with pancreatic cancer but further
evaluation is required in the frontline setting. 5FU with concurrent radi-
ation is more appropriate in patients with locally advanced disease.Answer 20.2.10. The answer is A.
BRCA2 is the most commonly mutated tumor suppressor gene in familial
pancreatic cancer followed by PALB2. K-RAS is an oncogene and not a
tumor suppressor gene. TP53 gene mutation is found in more than 70%
of all pancreatic cancers, but there is no evidence to link this mutation
with familial pancreatic cancer.Answer 20.2.11. The answer is A.
ABO blood type has been long known to be associated with increased risk
for lung cancer. A recent genome wide association study identified high
risk single nucleotide polymorphism for pancreatic cancer in the gene
encoding for the ABO blood type. Patients with nonpolyposis colorec-
tal cancer syndrome are at higher risk for gastrointestinal malignancies
including pancreatic cancer. K-ras mutation testing has so far not proven
to be effective in differentiating between pancreatic cancer and other con-
ditions such as pancreatitis and pancreatic adenoma.Answer 20.2.12. The answer is A.
Data on second-line treatment of patients with pancreatic cancer who
failed first-line gemcitabine are limited. Fluoropyrimidine (5FU or
capecitabine) and oxaliplatin combination has the most evidence for treat-
ment benefit in the second-line setting. Hence, a FOLFOX chemotherapy
regimen would be an appropriate second-line option in fit patients. Single-
agent erlotinib has not shown significant treatment benefit for patients
with metastatic pancreatic cancer. Raltitrexed is thymidylate synthase
inhibitor that is currently unavailable in the United States has shown
activity in the second-line setting in combination with irinotecan or oxali-
platin.Answer 20.2.13. The answer is E.
Telomere shortening is thought to predispose to chromosome fusion
(translocation) and missegregation of genetic material during the mitosis
and later during tumor genesis, telomerase is reactivated. SMAD4 (DPC4)
pathway mediates signals initiated on the binding of the extracellular pro-
teins TGF-.The underexpression of TGF-receptors results in cellular
resistance to the usual suppressive effects of the TGF-ligand. The cyclin
D oncogene complexes with CDKs and phosphorylates the retinoblas-
toma protein (tumor suppressive protein) that results in loss of negative
regulatory effect of retinoblastoma protein.