Oncogensis - Weir

Question 1

Define: Oncogenes

Answer 1

Genes in which mutations give rise to a gain of function or an enhanced level of function, leading to a malignancy. Mutated oncogenes are protooncogenes and usually encode growth or division promoting proteins

Question 2

Define: Tumor Suppressor Genes

Answer 2

Usually encode negative regulators of growth and proliferation that protect cells from malignancy

Question 3

Li-Fraumeni Syndrome

Answer 3

Mutation in p53 (a TSG); no “brake” on the system (no other info given)

Question 4

Cowden Syndrom

Answer 4

Mutation in PTEN (a TSG); removes a “brake” (no other info given)

Question 5

GIST (Gastrointestinal Stromal Tumor)

Answer 5

Due to mutation in c-Kit (an oncogene) (no other info given)

Question 6

Mutation in EGFR kinase

Answer 6

Important in many cancers but specifically for lung cancers; Erlontinib (Tarceva)

Question 7

Mutation in EML4-ALK

Answer 7

Lung Cancer; Crizotinib (Xalkori)

Question 8

Mutation in EGFR receptor signaling

Answer 8

Head and Neck Cancer (Tonsil Cancer example); Cetuximab (Erbitux)

Question 9

Goal is to inhibit VEGF in what cancer? What is treatment?

Answer 9

Glioblastoma; Bevacizumab (Avastin)

Question 10

Mutation in a VHL (not exclusive, just example given)

Answer 10

Renal Cell Carcinoma; Treat with Sunitinib (Sutent) to inhibit VEGF kinases

Question 11

9:22 translocation

Answer 11

Chronic Myeloid Lukemia; treat with inhibition of bcr-abl tyrosine kinase (no drug name given)

Question 12

How do you treat Estrogen Receptor positive breast cancer?

Answer 12

Tamoxifen

Question 13

What inhibits mTOR when inhibiting estrogen receptors no longer works?

Answer 13

Everolimus (Afinitor)

Question 14

How do you treat (HER-2) Estrogen Receptor negative breast cancer?

Answer 14

Trastuzumab (Herceptin); then Pertuzumab when HER-2 inhibitor no longer works

Question 15

How do you treat Prostate Cancer?

Answer 15

With the androgen receptor Enzalutamide (Zytiga)

Question 16

BRAF Mutation (B600)

Answer 16

Melanoma; Treat with Vemurafenib (Zelboraf)

Question 17

Mutation in Hedgehog system (PTCH Mutation)

Answer 17

Basal Cell Carcinomas; Treat with Vismodegib (Erivedge), a SMO inhibitor

Question 18

Many malignancies are caused by?

Answer 18

Mutation in oncogenes or TSGs

Question 19

Two inherited disorders predisposing to malignancies caused by mutations in TSHs are?

Answer 19

Li Fraumeni Syndrome and Cowden’s Syndrome

Question 20

One cancer accelerated by a c-Kit mutation is?

Answer 20

GIST (Gastrointestinal Stromal Tumor)

Question 21

Mutations in EGFR and ALK can lead to malignancies in a small percentage of what cancer?

Answer 21

Lung Cancer

Question 22

Usually multiple mutations are needed to overcome the body’s boundaries for what?

Answer 22

Cell Growth

Question 23

What can identify the mutation sites for many cancers and treat the problem specifically with targeted therapy?

Answer 23

Genomic Medicine

Question 24

Effective medicines have been made against specific targets in what cancers? 6 examples given

Answer 24

Breast, Lung, Head and Neck, Chronic Leukemias, Skin Cancers, and Brain Tumors

Question 25

What are very important targets in Breast and Prostate cancers?

Answer 25

Hormone Receptors

Question 26

Why are targeted treatments rarely curative?

Answer 26

When one pathway is targeted, mutations may develop to allow the cancer to progress around the therapy. Also, other pathways may increase to bypass the effect.