Formative Quiz 3 Review

Question 1

Combination chemotherapy is prescribed for a 45 year old man diagnosed with pancreatic cancer. One of the drugs prescribed is administered intravenously, and its mechanism of action is as a chain terminator for both DNA and RNA. The drug exhibits significant bone marrow suppression. The drug is:

Answer 1

Gemcitabine - Purine drugs are much harsher on the body

Question 2

Combination chemotherapy is prescribed for a 45 year old man diagnosed with acute myelocytic leukemia. One of the drugs prescribed is administered orally, and its mechanism of action requires incorporation into newly synthesized DNA and RNA. The drug exhibits very little bone marrow suppression. The drug is:

Answer 2

Both 6-mercaptopurine and 6-thioguanine are administered orally for treatment of leukemias, but only 6-thioguanine is actually incorporated into nucleic acids

Question 3

Combination chemotherapy is prescribed for a 38 year old woman diagnosed with ovarian carcinoma. One of the drugs prescribed is administered intravenously, and it causes metaphase arrest by stabilizing mitotic microtubules. The formulation of the drug elicits acute infusion reactions (inflammation and immune-based) and delayed bone marrow suppression. The drug is:

Answer 3

Both paclitaxel and vincristine act on microtubules and cause metaphase arrest, but paclitaxel stabilizes the microtubules, whereas vincristine destabilizes them.

Question 4

A 72 year old woman with non-small cell lung carcinoma was treated with standard cytotoxic chemotherapy, but did not experience an effective response. Her therapy now is changed to a single drug. The oral medication targets the EGF-R tyrosine kinase. The drug is?

Answer 4

Gefitinib targets EGFR- tyrosine kinase, and can be useful in treatment of non-small cell lung cancer. Based on the genetics of the patient and the tumor, however, it is most likely to be effective in patients who are female, non-smokers, and Asian.

Question 5

DNA testing of children is more likely to be indicated if…

1. the parents will know that they did not pass the gene to children
2. the parental testing is ambiguous
3. the condition predominantly develops in childhood
4. the test can be adequately interpreted
5. the test is inexpensive

Answer 5

There is no justification to test children, prior to their age of consent, unless there is a potential advantage to be gained for their knowing their medical condition so that early treatment can begin. Unfortunately, however, because of the difficulties associated with conducting clinical trials in children, the development of therapies that can be used in their treatment is lagging.

Question 6

A cancer is more likely to be a genetic family cancer syndrome if the family history includes…

1. cancer of the bone marrow
2. environmental exposures
3. late onset in an affected parent
4. unilateral cancer
5. young age of onset

Answer 6

Younger age of onset is characteristic of inherited cancer syndromes because every cell is carrying a mutant allele, giving the process a head-start. All that is necessary to fulfill the two-hits needed to initiate cancer development, is one more mutation in the normal allele. Inherited breast or colon cancers affect patients at a younger age and so it’s important to screen for the development of these cancers at an earlier age in these individuals. Gene testing will determine if a person is a carrier and therefore predisposed. Once gene testing has been done for an affected individual, other presymptomatic family members should be tested to assess their risk so that screening can be started earlier.

Question 7

Stromal fibrosis in response to invasion by a malignant neoplasm is known as?

Answer 7

Desmoplasia - Stromal fibrosis in response to invasion by a malignant neoplasm is known as desmoplasia. It is responsible for the firm to hard, often gritty, texture of some cancers

Question 8

Anaplasia is in reference to?

Answer 8

cytologic atypia of individual cells

Question 9

Dysplasia refers to

Answer 9

disordered growth of neoplastic epithelial cells confined by the basement membrane.

Question 10

Metaplasia refers to

Answer 10

replacement of one mature tissue type by another, usually in response to injury.

Question 11

Microsatellite instability is a marker for?

1. Increased tyrosine kinase activity
2. Defective DNA mismatch repair
3. Loss of p53 activity
4. Increased K-RAS activity
5. Loss of APC activity

Answer 11

Defective DNA mismatch repair

Question 12

Microsatellite instability is cause by what defective DNA mismatch repair enzymes

Answer 12

Defective DNA mismatch repair enzymes such as MSH2 and MLH1 lead to variably sized microsatellites (microsatellite instability)

Question 13

Is this true or not true in regards to X inactivation

involves activation of the XIST gene on the X chromosome that becomes inactive.

Answer 13

This is true

Question 14

Is this true or not in regard to X inactivation?

It affects the entire chromosome

Answer 14

This is false does not affect the entire inactivated X chromosome

Question 15

Is this true or not in regards to X inactivation:

is associated with methylation of the active X chromosome.

Answer 15

This is false it is associated with methylation of the inactive X chromosome.

Question 16

Is this true or not in regards to X inactivation:

can lead to disease symptoms in a heterozygous female if the proportion of inactivated Xm/Xp deviates strongly from 50/50.

Answer 16

This is true

Question 17

A patient begins anticoagulant therapy with a standard 6 mg/day dose of warfarin, but the response is a dangerously severe inhibition of coagulation (INR=8.5). The dose is decreased to 1.5 mg/day, and an appropriate therapeutic effect is seen. Which genotype could explain this result?

1. CYP2C9*1/*1
2. CYP2C9*3/*3
3. CYP2D6*1/*1
4. CYP2D6*3/*3
5. wild type VKORC1
6. mutant VKORC1

Answer 17

CYP2C9 metabolizes warfarin to an inactive form. Decreased activity of the homozygous CYP2C9*3 isoform would lead to higher levels of warfarin and decreased clotting.

Question 18

Combination chemotherapy is prescribed for a 32 year old man diagnosed with testicular carcinoma. One of the drugs prescribed is administered intravenously, and its mechanism of action blocks mitosis. The drug exhibits delayed bone marrow suppression and some neuropathy. The drug is:

1. Bleomycin
2. Docetaxel
3. Etoposide
4. Flutamide
5. Irinotecan

Answer 18

Docetaxel targets microtubules, stabilizing them so that they can form but not contract. This action blocks mitosis at metaphase. The adverse effect of neuropathy has been proposed to result from actions on microtubules in axons required for intracellular transport of organelles.

Question 19

What are the side effects of Docetaxel?

Answer 19

Delayed bone marrow suppression and some neuropathy

Question 20

A 63 year old woman with non-small cell lung carcinoma is treated with a single drug. The oral medication causes some transient dyspnea and a minor skin rash, but otherwise is well-tolerated. The drug is:

Answer 20

Gefitinib is a targeted therapy, and so has fewer and less severe adverse effects than do the traditional cytotoxic chemotherapy drugs.

Question 21

Resistance to anti-cancer drugs may be specific for a mechanistic class, or may confer broad resistance across several classes of drugs. Which of the following changes would confer multidrug resistance?

1. Amplification of DHFR
2. CYP2D6*3*3 genotype
3. Increased concentrations of glutathione
4. Induction of P-gp
5. Upregulation of p53

Answer 21

Answer D: P-glycoprotein (Pgp, MDR1) can export multiple classes of anti-cancer drugs, including antimetabolites, antibiotics, alkaloids, et al. MDR= multidrug resistance

Question 22

Which of the following activities is a critical determinant of therapeutic success for any cytotoxic cancer drug?

1. Activation of apoptosis
2. Induction of increased cellular glutathione concentrations
3. Inhibition of DNA repair processes
4. Interference with tumor invasiveness and metastasis
5. Stimulation of immune response

Answer 22

Most effective anticancer drugs activate apoptosis.

Question 23

A 38 year old man with testicular carcinoma is prescribed a multi-drug chemotherapy regimen. One drug is cell cycle-specific, causes DNA strand breaks, and can cause hypersensitivity reactions and cutaneous reactions. The dose-limiting toxicity of the drug is pulmonary fibrosis. This drug is:

Answer 23

Bleomycin and doxorubicin both target DNA and cause strand breaks, but the signature toxicity of doxorubicin is cardiac, whereas the toxicity of bleomycin is pulmonary.

Question 24

A patient with bladder cancer is treated with combination anti-cancer chemotherapy, including cis-platin. Since many anti-cancer drugs can cause acute nausea and vomiting, and this is particularly severe with cis-platin, the patient is pre-medicated to diminish the severity and intensity of this adverse effect. An effective drug for this purpose is:

Answer 24

Ondansetron - the 5-HT3 receptor antagonist, is effective in about 70% of patients and dramatically reduces acute nausea and vomiting caused by many anti-cancer drugs.

Question 25

What drugs is the 5-HT3 receptor antagonist that is meant to relieve nausea and vomiting in patients given drugs like cis-platin

Answer 25

Ondansetron

Question 26

A 69-year-old female patient is diagnosed with early stage breast cancer and immunohistochemistry staining of the tumor specimen indicates that her tumor is hormone-receptor positive (ER+/PR+) and HER2-negative. Which targeted therapy would you prescribe for the patient as a first-line treatment?

Answer 26

Tamoxifen or aromatase inhibitor - Use of tamoxifen or an aromatase inhibitor will allow there to be a back-up such as fulvestrant to be used should resistance develop.

Question 27

Which drug blocks estradiol signaling by degrading the estrogen receptor in target tissues?

Answer 27

**Fulvestrant** is an ER down-regulator and it induces a conformational change in the receptor that causes it to be degraded. It is prescribed as a 2nd line therapy for breast cancer treatment.

Question 28

Trastuzumab is a remarkably effective therapy for patients with HER2-positive breast cancers, both in the metastatic and adjuvant settings. However, not all women with tumors expressing high levels of HER2 respond to trastuzumab. Several potential mechanisms to explain trastuzumab resistance have been proposed. What can explain acquired trastuzumab resistance in breast cancer?

Answer 28

Excessive signaling through the insulin-like growth factor-1 receptor

Question 29

What are 3 ways that resistance for Trastuzmab be developed?

Answer 29

Resistance to trastuzumab can be caused by (1) **Steric effects or masking of the trastuzumab-binding sites.** The truncated form of HER2 (p95HER2) that lacks trastuzumab-binding domain can no longer be inhibited by trastuzumab. The remaining structure can still dimerize with other receptors and therefore can still trigger downstream cascades. (2) **Alternative elevations of other receptor tyrosine kinases**. The overexpression of other growth factor receptors, such as c-Met and IGF-1R, the two most commonly reported, can trigger similar effects on cell behavior, even though HER2 signaling is inhibited by trastuzumab. (3) **Intracellular alterations. In trastuzumab resistant cells, PTEN function is lost; thus, Akt is constitutively active. Also, resistant cells can harbor activating mutations in PI3K or Akt,** which can trigger other downstream signaling pathways even when HER2 is blocked by trastuzumab or when PTEN is active.

Question 30

During a routine physical exam, a 50-year-old male is found to have an abnormally high white blood cell count. Despite having no significant clinical complaints, subsequent blood work revealed that this patient was positive for the “Philadelphia chromosome,” and was therefore diagnosed with chronic myeloid leukemia. The oncogenic event that drives the development of CML is a result of:

Answer 30

A **translocation** between chromosomes 9 and 22 leads to the production of a fusion protein called Bcr-Abl. This “super-active” tyrosine kinase has unregulated kinase activity, leading to the oncogenic events seem in CML. Nearly all CML patients are positive for the Philadelphia chromosome, or t(9;22).

Question 31

After failing conventional therapies, a patient with advanced stage acute myeloid leukemia (AML) asks his doctor if he can start taking Imatinib, a new targeted therapy for leukemia, that he has heard being discussed in the news. This patient is positive for a 8;21 chromosomal translocation, and expresses the AML1-ETO fusion protein. Why did this patient’s doctor, a KUMC alum, correctly tell this patient that he was not a candidate for Imatinib? 1. Imatinib does not target the AML-ETO fusion protein. 2. Imatinib is a target for early-stage, not late-stage, AML. 3. Imatinib may only be used as a first-line (treatment-naive) therapy for AML. 4. Imatinib is a drug approved for lymphoma, not leukemia.

Answer 31

Imatinib is a drug designed to target a protein that is a result of a chromosomal translocation occurring in chronic myeloid leukemia (CML), not AML. **The fusion protein that Imatinib targets is Bcr-Abl, not AML1-Eto.**

Question 32

The benefits of cancer screening must be balanced by a variety of risks or harms associated with screening. Breast cancer screening by mammography is recommended for women of average risk aged 50-74 years. What is the primary reason that breast cancer screening is not widely recommended for younger women?

Answer 32

False positive screening results can lead to further diagnostic work-up

Question 33

Which of the following might be considered secondary prevention of cancer? 1. Reducing exposure to tobacco by quitting smoking at age 50 2. Increasing physical activity to reduce risk of colon cancer before the disease is present 3. Taking tamoxifen because your mother and sister have been diagnosed with breast cancer (even though you have not had breast cancer) 4. Wearing protective clothing and sunscreen when outside 5. Getting a screening mammography to promote early detection of breast cancer

Answer 33

The purpose of screening mammograms is to detect disease early and initiate treatment before disease progression. Secondary prevention involves detecting existing disease early in the disease process to prevent the development of adverse outcomes

Question 34

The goal of gene therapy is?

Answer 34

management and correction of human diseases by replacing defective genes with functional ones. By replacing defective genes with functional ones, it is possible to manage a genetic disease by providing the function, either in addition to the abnormality or as a complete replacement. In the best of circumstances, these would be permanent “cures.”

Question 35

An ideal gene therapy vector has all of the following characteristics EXCEPT: 1. The insert size consists of one or two genes. 2. High concentrations or titers can be produced. 3. An immune response is not elicited. 4. An appropriate amount of protein is produced. 5. Can be targeted to multiple cell types.

Answer 35

It would be a **disadvantage to target multiple cell types** in addition to the desired target because it could lead to unwelcome side effects, or “off-target” effects.

Question 36

Which of the following molecules is required for CD8+ T cells to recognize and target tumor cells? 1. CD20 2. CD25 3. CTLA-4 4. MHC class I 5. PD-1

Answer 36

To be recognized by a TCR, antigen must be presented by MHC.

Question 37

The most expensive and time-consuming task associated with the process of collecting and analyzing whole-genome sequencing data is 1. Isolation of DNA for sequencing. 2. Reverse-transcription of mRNA into DNA for sequencing. 3. The massively parallel sequencing itself. 4. Alignment and analysis of the sequencing data. 5. Storage of the raw sequencing data.

Answer 37

While each step in the process has significant cost, the most labor-intensive part of the process is the **bioinformatics analysis and follow up evaluation of gene function and determination of the associated risks of each of the candidate genes.**

Question 38

A variant most likely to be the cause of an inherited disease will be

Answer 38

**Rarely observed in most populations**. - Fortunately most disease-causing mutations are rare variants that are rare in most populations, with few exceptions. You cannot say that the variants are common if you also say that this one variant is “the” cause of a disease. Common variants that cause common diseases are themselves not alone as the cause of disease. They have to be inherited along with other variants and it’s the combination that causes the disease. Somatic mutation can be ruled out since we are talking about inherited disease. New or de novo mutations and X-linked mutations can be ruled out because they are minor causes of inherited disease compared to all rare variants.

Question 39

Of cells that enter the blood stream, which percentage most closely reflects the number of cells that will form metastases?

Answer 39

.01 %

Question 40

Your mom calls to share news that her friend from spin class has been diagnosed with ductal carcinoma in situ (DCIS). She’s curious to know what this means regarding the prognosis for her workout buddy. Which of the following statements is **NOT** true regarding DCIS? 1. Because it represents a stage 0 tumor, the prognosis for surviving these tumors is very good. 2. Because the tumor cells have just barely evaded through the basement membrane, the prognosis is very good. 3. Because the recurrence rate of these malignancies is low, the prognosis remains quite good. 4. These lesions are detected most often via mammography.

Answer 40

**Because the tumor cells have just barely evaded through the basement membrane, the prognosis is very good**. - DCIS, by definition, has not invaded the basement membrane at all. Invasion through the basement membrane would mean this tumor is no longer a DCIS, and is now an invasive ductal carcinoma (IDC).

Question 41

Following a recent diagnosis of invasive ductal carcinoma, your cousin calls you for expert medical advice regarding her diagnosis. Which of the following is true regarding invasive ductal carcinoma (IDC)? 1. Malignant, invasive cells are presented in the ductal tissue of the breast. 2. Because it arises in the ducts of the breast, it can only be detected using MRI. 3. It’s termed ductal carcinoma because the malignant cells stay within the confines of the ductal basement membrane. 4. Ductal carcinoma implies that the malignant cells have invaded from the surrounding fat tissue into the duct.

Answer 41

**1** - Invasive ductal carcinomas are, by definition, invasive and have invaded through the basement membrane. All breast cancer detection modalities (MRI, mammography, ultrasound) can detect IDC lesions; no technique is particularly better suited for the detection of specific histological subtypes of breast cancer.

Question 42

A 55-yr old female was recently seen in your clinic, and has questions regarding breast cancer screening for her teenage daughters. She tells you that breast cancer runs in her family, having an aunt and grandmother die of breast cancer. She’s curious about genetic testing for her daughters, stating that she must be a carrier of an inherited breast cancer gene given the high rate of breast cancer within her family. Which of the following statements best describes inherited breast cancer risks and the need for genetic testing? 1. If she’s not of Ashkenazi Jewish decent, then her risk of carrying an inherited breast cancer gene mutation are so low, the stress associated with testing outweighs the risks of testing. 2. BRCA1/2 genetic testing would be beneficial for this family to determine if the breast cancers that have occurred are linked to any known inherited genes. 3. The large majority of breast cancers are caused by inherited alleles, therefore, it’s very likely this woman is a carrier for a breast cancer susceptibility gene. 4. Whole genome sequencing would be more beneficial than specific gene testing because it may reveal previously unknown genetic polymorphisms.

Answer 42

**BRCA1/2 genetic testing would be beneficial for this family to determine if the breast cancers that have occurred are linked to any known inherited genes. -** Although inherited breast cancer risk alleles are higher in some ethnic populations than others, they are not exclusive to those populations. The majority of breast cancers are sporadic breast cancers; only a small percentage of cancers are due to inherited breast cancer genes. Whole genome sequencing to reveal previously unknown genetic polymorphisms would not give you any additional information that would be helpful to this patient, and may in fact cause undue stress.