Cancer - Campbell Flashcards Preview

Medical Biochemistry - 3 > Cancer - Campbell > Flashcards

Flashcards in Cancer - Campbell Deck (23):
1

Name two drugs first used in 1940 to treat acute lymphocytic leukemia that are still in use today. What metabolic pathway or pathways do they inhibit? What differentiates them from the most recently developed cancer therapies?

6-mercaptapurine (6-MP): Purine synthesis inhibitors and affects DNA replication

Methotrexate: Affects purine and thymidine synthesis

These older drugs are different from most recently developed cancer therapies in that they take the "shotgun"/ broad approach, whereas newer ways use targeted therapies.

2

Cushing syndrome is caused by an overgrowth of cells in the adrenal gland that produce cortisol. The tumor that results leads to overproduction of cortisol and increased drinking, eating, urination and enlarged, distended abdomen, "skull-like" look head. These tumors do not typically invade other tissues, remaining confined to an enlargement of the original area. Would Cushing syndrome be characterized as a cancer because it involves a tumor?

No. (By Bill)

3

Which of the following can sometimes be involved in the genesis of a cancer? (may have more than one answer)

A. Bacteria.
B. viruses.
C. inherited predispositions
D. gene defects
E. environmental causes (e.g. excess sunlight, some chemicals)

A. Bacteria
B. Viruses
C. inherited predispositions
E. environmental causes (e.g. excess sunlight, some chemicals)

4

Which of these is always involved in cancer?
A. Bacteria.
B. viruses.
C. inherited predispositions
D. gene defects
E. environmental causes (e.g. excess sunlight, some chemicals)

D. gene defects

5

When the gene for ras has a certain mutation, it gains activity (has increased function). Defects in this gene are also associated with cancer. Is the normal ras gene a tumor suppressor, an oncogene, an anti-oncogene, or a proto-oncogene? (more than one answer be correct)

Proto-oncogene

Protos are the normal form of growth signaling genes that can become oncogenes throug gain of function.

By Bill

6

When the gene for ras has a certain mutation, it gains activity (has increased function). Defects in this gene are also associated with cancer. Is the mutant ras gene a tumor suppressor, an oncogene, an anti-oncogene, or a proto-oncogene?

Oncogene (A normal gene can be a proto, but only after gaining a function (mutation) does it become an oncogene)

by Bill

7

When the APC gene has a certain mutation, it loses activity (has reduced function). Defects in this gene are also associated with cancer. Is the normal APC a tumor suppressor, an oncogene, an anti-oncogene, or a proto-oncogene (more than one answer may be correct)?

Anti-oncogene / tumor suppressor

Same thing! Normal activity must decrease cancer if reduced activity increases it! (By Bill)

8

When the APC gene has a certain mutation, it loses activity (has reduced function). Defects in this gene are also associated with cancer. Is the mutant APC a tumor suppressor, an oncogene, an anti-oncogene, or a proto-oncogene? (more than one answer may be correct)

I think it may still be an anti-oncogene, because although it has lost function , it is still functioning in some capacity. Maybe?

By Bill

9

What does the gene p53 do? What happens when it gets knocked out (i.e. "loss of function)"?

Gene p53 regulates the checkpoint between G1 and S phase in the cell cycle. When gene p53 is knocked out, cancer occurs.

10

The loss of function of what two genes have a 1% relationship to colorectal cancer?

HMLH1 and HMSH2 are DNA repair genes that become defective and result in cancer

11

BRCA1 is a gene discovered in 1994 that when even one defective copy is inherited predisposes to breast and ovarian cancer, and to a lesser extent pancreatic cancer. BRCA1 has a role in cell cycle arrest in response to DNA damage (i.e. BRCA1 participates in halting cell division while certain types of DNA damage are being repaired. Would this make BRCA1 a proto-oncogene, an oncogene, or an anti-oncogene?

BRCA1 is an anti oncogene.

By Bill

12

The human platelet derived growth factor receptor beta (PDGFRbeta) is a receptor involved in vascular system development. One of its normal roles is in promoting proliferation of vascular smooth muscle cells surrounding endothelial cells of developing blood vessels. Explain why it might be a proto-oncogene and how it might become an oncogene.

It is a proto-oncogene because it normally promotes cell proliferation. If its function was enhanced it could go out of control and become an oncogene.

By Bill

13

Make a list of all examples from class of cell cycle control genes, all growth signal transduction genes, and all DNA repair genes that when defective may contribute to the development of cancer. Which are cell cycle, which are growth signaling and which are DNA repair genes?

Cell Cycle Control-
P53 (controls checkpoint between G1-S)

Growth Signal Transduction-
HER2

DNA Repair-
hMLH1
hMSH2

(Bill)

14

Name some characteristics of matrix metalloproteinase proteins. What process associated with cancer are matrix metalloproteinases involved in?

Characteristics: enzymes that cut proteins in the extracellular matrix that require metal ions to function.

Involved in Metastasis. (By Bill)

15

Explain the mechanism discussed in class by which cancer cells may evade apoptosis.

Cancer cells evade apoptosis by up-regulating XIAP (x-linked inhibitor of apoptosis).

16

Agent 99 is a promising new candidate for cardiovascular disease. Agent 99 stimulates angiogenesis and thus aids blood circulation to areas served by blood vessels that have been blocked by atherosclerosis. Would this make a good cancer chemotherapeutic agent and why?

a. Yes, because in cancer cells apoptosis and angiogenesis are often increased so the cancer cell will not die.
b. No, cancer cells may even benefit from increased blood supply.
c. No, improved cardiac function will increase metastasis.
d. Yes, because it would cure both heart disease and lung cancer.
e. Yes, and many stimulants of angiogenesis are in clinical trials to test their efficacy in fighting cancer.

b. No, cancer cells may even benefit from increased blood supply.

(By Bill)

17

The OSI Pharmaceuticals/Genentech product Tarceva (erlotinib) was approved in the fall of 2004 for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen and advanced pancreatic cancer. Tarceva is a small molecule taken in tablet form that specifically inhibits the kinase activity of human epidermal growth factor receptor (EGFR or HER-1). Will Tarceva likely prove effective and be approved for treatment of other cancers such as small-cell lung cancer and breast cancer, and why?

A. Yes, since the human epidermal growth factor receptor 2 (HER-2) gene is over-expressed in many other cancers, breast cancer being one example.
B. Yes, because Tarceva is a brand new drug designed with all our new knowledge of the molecular basis of cancer to have wide application in cancer chemotherapy.
C. Yes, because p53 is also a plasma membrane-spanning kinase, and is defective in more cancer tumors than any other gene.
D. No, because unfortunately few cancers may be treated by a drug that may be administered in such a convenient form as a table.
E. No, because the genes defective in other cancers such as small-cell lung cancer and breast cancer are typically different than those defective in non-small cell lung cancer.

...

18

You are meeting with a breast cancer patient and her family to discuss treatment options. They have heard of Herceptin and inquire about its use. The pathology report for that patient included a biopsy that indicated Herceptin would not be effective. Which of the following would be your best response?

A. Herceptin should be given to this patient despite the pathology report, just in case it works.
B. The pathologist said it shouldn't be used, and they are the expert.
C. The mechanism of Herceptin is to block a receptor that is overexpressed in some patients. In this patient, the receptor is not overexpressed, so the drug will be of no use.
D. The mechanism of Herceptin is to block a DNA repair enzyme that is overactive in some patients. In this patient, the DNA repair enzyme is not overactive so the drug will be of no use.
E. Since cancer drugs have few side effects, ti would be okay, but expensive (a course of treatment is ~$50k to >$100k) to use if the patient and family really want.

C. The mechanism of Herceptin is to block a receptor that is overexpressed in some patients. In this patient, the receptor is not overexpressed, so the drug will be of no use.

Herceptin inhibits HER-2
By Bill

19

"Loss of function" gene

Anti-oncogene

20

"Growth signal transduction gene"

Proto-oncogene

21

"DNA repair gene", "cell cycle control gene"

Tumor suppressor = Anti-oncogene

22

Cancer does what to angiogenesis? What is a type of angiogenesis inhibitor?

Increase new blood vessel growth.

Avastin is an angiogenesis inhibitor.

23

Who will get an A on this exam?

Karin Hwang

(By Bill)