Cancer as a Chronic Disease

Question 1

List 3 mehcnaisms of drug resistance in cancer.

Answer 1

1 - New mutations.

2 - Use of alternative signalling pathways.

3 - Presence of cancer stem cells.

Question 2

How can cancer stem cells confer drug resistance in cancer?

Answer 2

• After chemotherapy treatment, the differentiating cells are eliminated and the cancer stem cells remain (as most of the stem cells are not undergoing the cell cycle).
• The cancer stem cells are therefore able to replenish the population of cancer cells after cessation of treatment.

Question 3

List the types of tumour hetereogeneity.

Answer 3

1 - Intratumourial heterogeneity.

2 - Intermetastatic heterogeneity.

3 - Intrametastatic heterogeneity.

4 - Interpatient heterogeneity.

Question 4

Define intratumourial heterogeneity.

Answer 4

Intratumourial heterogeneity refers to heterogeneity within the same tumour specimen.

Question 5

Define intrametastatic heterogeneity.

Answer 5

Intrametastatic heterogeneity refers to heterogeneity within each different metastatic lesion.

Question 6

Define intermetastatic heterogeneity.

Answer 6

Intermetastatic heterogeneity refers to heterogeneity between metastases.

Question 7

Define interpatient heterogeneity.

Answer 7

Interpatient heterogeneity refers to heterogeneity between cancer patients - no two cancer patients have an identical clinical course.

Question 8

What are conditionally replicating viruses?

Answer 8

• Conditionally replicating viruses are viruses that infect both normal and tumour cells but can only replicate in tumour cells.
• The progeny viruses therefore go on to kill surrounding tumour cells.

Question 9

What is lapatinib?

What is the target of lapatinib?

What is it often coadministered with? Why?

Answer 9

• Lapatinib is a small molecule tyrosine kinase inhibitor.
• Lapatinib targets both ErbB1 (an EGFR) and HER2.
• Lapatinib is often coadministered with trastuzumab, and anti-HER2 mAb in order to enhance apoptosis of HER2-overexpressing breast cancer cells.

Question 10

What is cetuximab?

Describe its mechanism of action.

Which gene mutation reduces the effectiveness of cetuximab?

Answer 10

• Cetuximab is an anti-EGFR mAb approved for EGFR-expressing colorectal cancer and squamous cell carcinoma of the head and neck.
• It binds to the extracellular domain of an EGFR to prevent ligand binding and dimerisation.
• The presence of KRAS mutation predicts an adverse outcome in response to cetuximab.

Question 11

What is the WHO’s definition of chronic disease?

What are the 4 main types of chronic disease?

Answer 11

A chronic disease is a disease that is:

1 - Not passed from person to person.

2 - Of long duration.

3 - Of slow progression.

• There are 4 main types of chronic disease:

1 - Cancers.

2 - Cardiovascular disease.

3 - Chronic respiratory diseases.

4 - Diabetes.