Chemo cumulative midterm exam

How does UV light cause cancer?

Pyrimidines dimers are formed in DNA causing mutations

What are proto-oncogenes?

Like Thanos, requiring all the power to cause harm

What are tumor suppressor genes?

Guardians of the genome

What are the 8 hallmarks of cancer talked about in depth in class?

• Sustaining proliferative signaling

• Evading growth suppressors

• Resisting cell death

• Enabling replicative immortality

• Inducing angiogenesis

• Activating invasion and metastasis

• Deregulating cellular energetics

• Avoiding immune destruction

What is the major enzyme involved in apoptosis?

Caspase

Apoptotic cell death can be induced by?

• P53 signaling

• Signaling from surface cell death receptors

• Extra/intra cellular stresses

What is the process of new blood vessels called?

Angiogenesis

Which of the following is most likely true of aggressively dividing cancer cells?

• They do not express telomerase

• They do not express hTERT

• They are in a state of cell crisis

• Their telomeres are stabilized (not shortening with each cellular division)

• None of the above

Their telomeres are stabilized (not shortening with each cellular division)

Which posttranslational modification is especially important for therapeutic antibodies?

Glycosylation

What is the difference between a nucleoside and nucleotide?

Nucleosides lack a phosphate group

True or false: primary toxicities associated with capecitabine involve diarrhea and hand-foot syndrome.

True

5-fluorouracil (5-FU):

1. Inactive in its parent form; therefore 5-FU is a "prodrug".

2. An active metabolite 5-fluor-2'-deoxyuridine-5'-monophosphate (fdUMP) binds covalently with methylenetetrahydrofolate which inhibits DNA synthesis

3. Both

4. Neither

Both

Characteristics of newer folic acid analogues: example - Pemetrexed and Pralatrexate

1. Inhibition of thymidylate synthase

2. Enhanced transport into tumor cells

3. Neither

4. Easy digestion

Inhibition of thymidylate synthase

MTX-PG display increased inhibitory effects than MTX alone? Why?

1. Increased action on DHFR

2. Increased TS inhibition

3. Increased cell retention

4. Increased transport to cell

Increased cell retention

Infections associated with 6-mercaptopurine and azathioprine administration:

Fungal infections and pneumocystis pneumonia

What is the primary 6-mercaptopurine toxicity?

Bone marrow depression

What is the primary toxic metabolite derived from cytarabine (Ara-C)?

Ara-CTP

What is the most important antimetabolite type agent used to treat AML?

Cytarabine

What is the Warburg effect?

Anaerobic glycolysis in aerobic environment

Cancer cells make glucose in glycolysis under aerobic

conditions

What is cytokinesis?

Division of the cytoplasm

What brain region is stimulated during emesis to cause vomiting?

Chemoreceptor trigger zone

Mitosis is a process of?

Nuclear division

Derivative from the Western Yew and European Yew tree, this anticancer drug acts by inhibiting tubulin de-polymerization:

a. Vincristine

b. Paclitaxel

c. Methotrexate

d. Vincan Alkaloids

Paclitaxel

Which one(s) of the following statements is/are correct?

A.	Taxanes are classified as microtubule stabilizing agents
B.	Both docetaxel and paclitaxel exhibit resistance to the P-glycoprotein reflux pump the activity of which results in resistant to the anti-cancer activity of these agents.
C.	Both
D.	Neither

Both

Peripheral neuropathy represents a common and dose-limiting toxicity of anti-microtubule drugs, likely due to direct action on microtubules.

1. True

2. False

True

The chemotherapy undertaken by this patient caused acute hemorrhagic cystitis. Which drug was most likely to be responsible for this toxicity?

A.	Doxorubicin
B.	Cyclophosphamide
C.	Methotrexate
D.	Vincristine

Cyclophosphamide

High expression of this enzyme confers in cancer cells resistance to nitrosoureas (Carnustine) as well as other methylating agents.

A.	DNA polymerase
B.	Thymidylate synthase
C.	Dihydrofolate reductase
D.	Alkyl guanine alkyl transferase
E.	Topoisomerase II
F.	Topoisomerase I
G.	Xanthine Oxidase

Alkyl guanine alkyl transferase

Which one(s) of the following statements is/are correct?

A.	Taxanes are classified as microtubule stabilizing agents
B.	Both docetaxel and paclitaxel exhibit resistance to the P-glycoprotein reflux pump the activity of which results in resistant to the anti-cancer activity of these agents.
C.	Both
D.	Neither

Both

Major type origin of cancer?

Epithelial

If a tumor’s cells have dedifferentiated (lost all tissue-specific traits), its origin cannot be readily identified; such tumors are said to be

Anaplastic

Causes formation of pyrimidine dimers in the DNA leading to mutations.

UV light

The characteristic tumor associated with asbestos

Malignant mesotheliom

Generally ONLY TOXIC TO CELLS IN S PHASE

Antimetabolites

Inhibits DHFR

Methotrexate

Toxicity mirrors that of methotrexate, with the additional feature of a prominent erythematous and pruritic rash in 40% of patients.

Pemetrexed

Can be taken up by cells as bases, and can be converted by the cells into (deoxy) nucleosides/nucleotides

Uracil and guanine

It is the single most effective agent for induction of remission in AML disease

Cytarabine

Deficiency or lack of the activating enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT)

6-mercaptopurine

Oral doses of 6-MP should be reduced by 75% in patients receiving the xanthine oxidase inhibitor, allopurinol.

True

Binds to β-tubulin, which hinders the binding of α-tubulin to β-tubulin of microtubules

Vinca alkaloids

What is choriocarcinoma?

Cancer of the placenta

Transformed into SN-38 through the action of a carboxylesterase and inactivated by glucuronidation

Irinotecans

Too much of doxorubicin causes what to happen?

Cardio toxicity

Causes hemorrhagic cystitis often seen during therapy with cyclophosphamide

acrolein

Responsible for antitumor effects

Phosphoramide mustard

Counteracted by mesna (2-mercaptoethane sulfonate) and diuresis

Toxicity of cyclophosphamide

The most neurotoxic of all nitrogen mustards (due to significant generation of chloroacetaldehyde

Ifosfamide: adverse effect --> hemorrhagic cystitis

Used against tumors of the brain and meninges

Nitrosoureas

Alkylation can be repaired by the repair enzyme O6-alkyl guanine alkytransferase (AGT)

Nitrosoureas

AGT: O6-alkylguanine DNA alkyltransferase is a protein that in humans is encoded by the O6 methylguanine DNA methyltransferase (MGMT) gene.

Dacarbazine

Aluminum in the needle can inactivate this drug

Cisplatin

SERM therapy exerts estrogenic effect in most non-breast tissues and may lead to the risk of endometrial cancer

True

Aromatase inhibitors are also known as “pure anti-estrogens”

False

What are the key regulators of transition between cell cycle phases?

A.	Tyrosine Kinases (TK)
B.	Cyclin Dependent Kinases (CDKs)
C.	Caspases
D.	Serine/Threonine proteases

Cyclin Dependent Kinases (CDKs)

Pegylation of Asparaginase can reduce the antigenicity of the enzyme.

True

Resistance to anticancer effects of L-asparaginase may occur through tumor cell synthesis of asparagine synthatase.

True

Choose the correct statement/statements concerning hydroxyurea:

A.	Classified as an antimetabolite
B.	Prevents conversion of ribonucleotides to deoxyribonucleotides.
C.	Both
D.	Neither

Prevents conversion of ribonucleotides to deoxyribonucleotides

The enzyme which is very low or absent in all the lymphoblastic cancer cells and may lead to the inhibition of protein synthesis?

A.	Asparaginase
B.	Asparagine synthetase
C.	Ribonucleotide reductase
D.	Crisantaspase

Asparagine synthetase

The inhibitory action of Letrozole on aromatase enzyme by substrate competitive mechanism

True

Retinoids are classified as this type of anticancer agent.

A.	DNA polymerase inhibitor
B.	Promoter of cellular differentiation
C.	Alkylating agent
D.	Topoisomerase inhibitor

Promoter of cellular differentiation

Which of the following molecules are more likely to trigger the generation of neutralizing antibodies in a patient?

1. Hydroxyurea

2. Asparaginase

3. Asparagine

4. Nitrosoureas

Asparaginase

Which Mab has the “chimeric” structure?

A.	Alemtuzumab
B.	Ipilimumab
C.	Blinatumomab
D.	Rituximab

Rituximab

Cetuximab is not recommended for patients with activating KRAS or BRAF V600E mutations because

A.	The mutant KRAS could activate the Downstream pathway of MAPK without the activation of EGFR
B.	Cetuximab is not targeted to EGFR
C.	Cetuximab is a chimeric antibody
D.	Cetuximab is not approved by FDA for cancer treatment

The mutant KRAS could activate the downstream pathway of MAPK without the activation of EGFR

Which antibody inhibits HER2 receptor dependent signaling? 

A.	Rituximab
B.	Cetuximab
C.	Bevacizumab
D.	Trastuzumab

Trastuzumab

Bevacizumab is a monoclonal antibody used in cancer therapies. Choose the most appropriate statement. 

A.	Binds to VEGF which blocks signaling from VEGF-R (Receptor)
B.	Binds to VEGF-R (receptor) which inhibits VEGF dependent signaling
C.	Interacts with the tyrosine kinase domain of VEGFR and inhibits downstream signaling
D.	Interacts with nuclear receptor and inhibits cell proliferation

Binds to VEGF which blocks signaling from VEGF-R (receptor)

hyperplastic

a benign tumor that is described as being an increase in the number of cells to make a tissue or organ larger

metaplastic

a benign tumor that is described as having cells that adapt or change types due to its hostile environment

hypertrophy

a benign tumor that is described as being an increase in the size of individual cells to make a tissue or organ larger

dysplastic

a benign tumor described as having the presence of abnormal cells within a tissue by mutation, but still somewhat differentiated

what is the most important risk factor for cancer

age

what is an oncogene

a cancerous gene that results in a cancer protein

DNA excision repair

DNA with mutations in it are taken out and replaced by the correct sequence

How do defects in DNA affect UV light mutations

the pyrimidine dimer mutations aren’t repaired

what is neoplastic transformation

new progressive growth of defective cells; cancer cells turn good cells bad

Proto-onco genes

genes that are prone to mutations

Why are BRAF mutations bad for some drugs

they make constant signaling to EGFR internally while some drugs only target external receptors

What is the guardian of the genome and what is its function

P53 induces apoptosis/repairs where need be

what is the gatekeeper of the cell cycle and what is its function

retinoblastoma associated protein

tells the cell cycle to continue or stop

extravasation

transit via lymph and blood followed by escape from vessels into distant parenchyma

senescent

alive but non-proliferative

interphase

growth phase

G1

normal cell growth and function

S

DNA synthesis occurs

G2

checks of DNA and prepping for mitosis

mitosis

splitting of the nucleus

What is the target for methotrexate

folate

methotrexate-PG display increased inhibitory effects than methotrexate alone. Why?

it’s stuck in the cell so it’s able to target more processes and do more damage

what are dNTP’s

DNA bases basically

what is the function of leucocoverin

a drug that stops the toxicity of methotrexate

what is the main form of resistance for pretty much any cancer drug

efflux of the drug transporter

what are the bases that can only be taken up by cells as nucleosides or nucleotides

adenine, guanine, and cytosine

what is DPD

it is important for the metabolism and elimination of 5-FU

capecitabine is the pro drug for what

5-FU

what does Ara (cytarabine) do when it binds

activates kinase checkpoints in the cell cycle to induce apoptosis

what is the drug used in combo therapy for pancreatic cancer and has a better and longer survival rate for pancreatic cancer than gemcitabine

folfirinox

what drug binds to beta-tubulin but doesn’t stop it from binding to alpha tubulin, and instead just disassembles the microtubules

taxols

what drug has the lowest incidence of allergic reaction

nab-paclitaxel

Bevacizumab

binds to VEGF-A and blocks ligand dependent activation

prevents blood vessel proliferation

for glioblastoma patients

bleeding, high blood pressure

ramucirumab

binds to VEGFR2 and blocks binding of VEGFR ligand —> inhibits ligand induced activity in endothelial cells

used in combo with chemotherapy for metastatic colorectal cancer

platelet-derived growth factor receptor

important in stem cell growth

regulate cell proliferation, differentiation, cell growth, and development