Devita, Hellman, and Rosenberg's Cancer

LWBK1006-08 LWW-Govindan-Review December 12, 2011 18:49

102 DeVita, Hellman, and Rosenberg’s CANCER: Principles and Practice of Oncology Review

Answer 8.16. The answer is A.

Both KRAS and BRAF V600E mutations are associated with development

of resistance to cetuximab in the treatment of patients with colorectal

cancer. EGFR-TK mutations are uncommon in patients with colorectal

cancer, and NFB activation results in pro-apoptotic signaling; however,

it has not been shown to be associated with development of resistance to

cetuximab in patients with colorectal cancer.

Answer 8.17. The answer is B.

The growth of cells is significantly faster in the early part of the growth

curve enabling chemotherapy to cause a greater log cell kill. Dose-dense

chemotherapy, by administering cytotoxic drugs more frequently, can pro-

duce greater effects on smaller volume tumors.

Answer 8.18. The answer is B.

Normal bone marrow and GI precursor cells possess intact genetic

machinery to undergo apoptosis, repair DNA damage, and halt cell-

cycle progression. Therefore, cells that have been damaged by chemother-

apy undergo programmed cell death and are not allowed to continue on

through the cell cycle.

Answer 8.19. The answer is C.

p53 is a tumor suppressor gene that mediates apoptosis in cells with DNA

damage. It plays a role in G1 and G2 arrest of the cell cycle after exposure

to cytotoxic agents.

Answer 8.20. The answer is A.

Recent evidence has suggested that mechanisms of drug resistance are

due to gene mutations in cell-cycle regulatory pathways rather than drug-

specific mutations. Wild-type p53 acts as a tumor suppressor of the mdr-1

gene. Increasing growth rates may lead to increased drug resistance as the

result of more rapid entry of cells into the cell cycle.

Answer 8.21. The answer is D.

Caspase activation occurs through the activity of the intrinsic and extrin-

sic pathways of apoptosis. Bcl-2 is involved in the intrinsic pathway, and

tumor necrosis factor mediates the extrinsic pathway. p53 is a tumor sup-

pressor gene involved in the early activation of the programmed cell death

pathway.

Answer 8.22. The answer is A.

Imatinib inhibits bcr-abl, platelet-derived growth factor, and c-kit. It

is used to treat chronic myeloid leukemia and GI stromal tumors that

express the c-kit TK.