Devita, Hellman, and Rosenberg's Cancer

LWBK1006-02 LWW-Govindan-Review November 24, 2011 11:18

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

Answer 2.30. The answer is B.

IL-6/8 is thought to be secondarily angiogenic. TSP-1, DLL4, and vaso-

hibin are all shown to inhibit angiogenesis. Embryologic studies have

shown that Notch/DLL4 is important in early angiogenesis; however, in

the adult, it has been shown to be an inhibitor of tumor angiogenesis.

Answer 2.31. The answer is A.

The effectiveness of antiangiogenic therapy is profoundly reversed dur-

ing episodes of drug-free breaks. This is thought to be mediated by the

rapid mobilization and homing of ECs to the drug-treated tumors. This

has led to the concept of metronomic low-dose chemotherapy. By reduc-

ing or eliminating altogether drug-free periods with continuous low-dose

chemotherapy, the rapid reversal of antiangiogenic therapy may be pre-

vented.

Answer 2.32. The answer is A.

There are four currently proposed mechanisms by which tumors over-

come antiangiogenic therapy. Tumors possess proangiogenic growth fac-

tor redundancy, so targeting one pathway of angiogenesis may not

completely eliminate the ability of tumors to produce new vasculature.

Decreasing the ability of the tumor to develop new vessels may also

select for mutant/variant tumor subpopulations that are more resistant

to hypoxia. Further, antiangiogenic therapy targets newly formed blood

vessels. Tumors may exploit existing organ vasculature to obtain neces-

sary oxygen and nutrients. Lastly, targeting newly forming blood vessels

may accelerate the maturation and remodeling of already existing blood

vessels. This may produce a more stable vascularity in tumors.

Answer 2.33. The answer is B.

Antiangiogenic therapy is not without side effects. Anti-VEGF therapy

has been shown to lead to specific toxicities, such as hypertension, pro-

teinuria, bowel perforation, hemorrhage, arteriothrombotic events, and

others. Among these, aplastic anemia has not been documented.

Answer 2.34. The answer is D.

Tumor grade, depth of invasion, and lymphovascular invasion all carry

a higher risk of metastasis. Proper immune function would hinder the

development of metastasis because CTCs would be targeted for destruc-

tion.

Answer 2.35. The answer is B.

By using radioactive nucleotides incorporated into tumor DNA, it has

been shown that less than 0.01% of tumor cells can give rise to metastases.

Answer 2.36. The answer is B.

Metastasis progression genes promote tumor metastases among other

functions. Tumorigenic genes are genes that promote primary tumor