Devita, Hellman, and Rosenberg's Cancer

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

Chapter 2•Molecular Biology of Cancer Part 2 27

immunodeficiency, increased sensitivity to radiation, and a predisposition

to lymphoid malignancies. VHL is caused by a mutation in the pVHL

tumor suppressor gene causing development of sporadic hemangioblas-

tomas and clear-cell renal carcinomas. Familial malignant melanoma syn-

drome is caused by mutation in CDKN4A, the gene encoding p16.

Answer 2.12. The answer is B.

Apoptosis is a genetically programmed means of rapid and efficient killing

of unnecessary or damaged cells. It is characterized by cell shrinkage,

blebbing of the plasma membrane, chromatin condensation, and intranu-

cleosomal DNA fragmentation without being followed by surrounding

inflammation.

Answer 2.13. The answer is D.

The death receptor pathway is involved in the modulation of apoptosis.

It involves the ligands TNF, Fas, TRAIL, and their receptors. Noxa is a

member of the BH3-only protein family and can induce apoptosis.

Answer 2.14. The answer is B.

Taxanes specifically induce apoptosis by stimulating Bim expression.

Nbk/Bik stimulates apoptosis by inhibiting protein synthesis. Puma and

Noxa mediate apoptosis by p53 activation. After growth factor with-

drawal, Bad stimulates apoptosis.

Answer 2.15. The answer is A.

Sorafenib directly inhibits RAF, thereby causing MAP kinase inhibition

and restoring apoptotic function. Imatinib mesylate, by means of blocking

the constitutively active tyrosine kinase activity of the Bcr/Abl fusion gene,

restores Bim and Bad apoptotic function. Bortezomib is a proteosome

inhibitor that blocks Bim degradation, knowing it to induce apoptosis.

Taxanes induce apoptosis by stimulating Bim expression.

Answer 2.16. The answer is A.

Bcl-2 inhibitors like ABT-737 binds to the BH3-binding pocket of Bcl-2,

Bcl-xL, and Bcl-w, thereby blocking the antiapoptotic effect of Bcl-2.

ABT-737 exhibits some activity against some human lymphomas and

small cell lung cancers in vitro. Inhibition of the tyrosine kinase activity

of Bcr/Abl is accomplished through imatinib mesylate. Taxanes stimulate

Bim expression, restoring apoptosis. Bortezomib blocks the proteosomal

degradation of Bim.

Answer 2.17. The answer is D.

Tumor cells generally have a reduced metabolic capacity that is frequently

coupled with high-energy demand sustaining rapid cell growth. One

means for specifically targeting tumor cells is through therapeutic nutrient

deprivation. This is the basis for the use of angiogenesis inhibitors.