Cancer Drug Resistance Exam Questions with Detailed Answers Latest Update 2024 (Already Passed)
What is the phrase related to cancer that Tolstoy mentioned in the opening lines of Anna Karenina? (Not
really, but prof included this) - Answers "Normal cells all respond similarly to drugs, but cancer cells each
respond in their own ways."
What are current cancer treatments? - Answers Surgery, cytotoxic chemotherapy, targeted therapy,
radiation therapy, endocrine therapy and immunotherapy
What are the two types of resistances that are responsible for cancer relapses? - Answers Intrinsic drug
resistance (exists before treatment) and acquired drug resistance (appears after therapy)
What is multidrug resistance? - Answers The development of both resistance and simultaneous cross-
resistance to a wide range of functionally and structurally unrelated chemotherapeutic drugs
What are the two categories for drug resistance? - Answers Intrinsic vs extrinsic
- Intrinsic resistance exists before drug therapy while acquired resistance is induced after therapy
What factors can lead to intrinsic resistance? - Answers -Pre-existing (inherent) mutation that decrease
responsiveness of cancer cells
- heterogeneity of tumors with pre-existing insensitive subpopulation of cells
- activation of intrinsic pathways used as defense against environmental toxins
T/F defective p53 pathway increases resistance to DNA damage agents - Answers T
This is one cause of intrinsic resistance
What transcriptional repressors mediate epithelial-to-mesenchymal transition, making cancer cells more
resistant to treatment? - Answers Snail and Slug
How are cellular detox pathways beneficial to cancer cells? - Answers Although cellular detox pathways
are typically used as a defense agains environmental toxins, they are used by cancer cells to eliminate
cytotoxic effects of anticancer drugs
T/F Mechanisms of acquired drug resistance tend to be similar than those of pre-existing (intrinsic) drug
resistances - Answers False; they tend to be totally different
What factors can acquired resistance be a result of? - Answers -Activation of second (non-targeted)
proto-oncogenes that becomes the newly tumor driver
-mutations or altered expression levels of the drug target
, -changes in tumor microenvironment after treatment
What is considered to be the major reason for chemotherapy resistance? - Answers Elevated efflux of
anticancer agents which result in decreased intracellular drug levels
What is responsible for drug efflux and what superfamily are they from? - Answers Transmembrane
transporters; primarily from the ATP binding cassette (ABC) transporter superfamily.
How many ABC genes does the human body have? - Answers 48 ABC genes that are classified into seven
subfamilies
Which is the most well-characterized ABC transporter? - Answers ABCB1 (MDR1 or P-gp)
What does ABCB1 consist of and what can it do? - Answers ABCB1consists of two transmembrane
domains forming a passage for substrates in addition to two nucleotide binding domains that bind and
hydrolyze ATP. ABCB1 has multiple drug binding sites that can bind and pump a wide variety of
structurally-unrelated drugs from the cell.
T/F ABCB1 can bind and pump a wide variety of structurally-unrelated drugs from the cell - Answers
True, it has multiple drug binding sites
What is commonly seen during application of targeted therapies which block the growth of cancer cells
by inhibiting the activity of specific target proteins involved in tumor development? - Answers What is
frequently seen is alteration of drug targets wither through secondary mutation in the target protein or
by changes in the expression levels due to epigenetic alterations
What is the relationship between lung cancer and secondary resistance? (example with EGFR) - Answers
within 1 year of EGFR inhibitor treatment, 50% of pts develop a T790M mutation on EGFR which leads to
resistance of 1st and 2nd generations of TKIs. There are currently 4 generations on the market to
combat secondary resistance.
What is the relationship between breast cancer and secondary resistance? - Answers Tamoxifen
(compete with estrogen for ligand binding site of ER) resistance develops in pts receiving treatment
(with TX). This led to the development of aromatase inhibitors which interfere with the last step of
estrogen synthesis.
what is the mechanism of action for most chemotherapy drugs? - Answers They kill cancer cells by
inducing DNA damage.
How does the DNA damage response lead to resistance to cancer drugs? - Answers The DNA damage
response (DDR) of affected cells to the anti-cancer drugs may result in reduced efficacy of the drugs by
DNA lesion repairs, leading to drug resistance. Numerous genes involved in DNA repair were found to be
upregulated in 5-FU resistant human colon cancer cell lines. 5-FU treatment induced upregulation of
p53-target genes on DNA damage response and repair. Success to repair the damages led to reduced
cell cycle arrest and apoptosis in the resistant cell lines compared to parental cell lines.
What is the phrase related to cancer that Tolstoy mentioned in the opening lines of Anna Karenina? (Not
really, but prof included this) - Answers "Normal cells all respond similarly to drugs, but cancer cells each
respond in their own ways."
What are current cancer treatments? - Answers Surgery, cytotoxic chemotherapy, targeted therapy,
radiation therapy, endocrine therapy and immunotherapy
What are the two types of resistances that are responsible for cancer relapses? - Answers Intrinsic drug
resistance (exists before treatment) and acquired drug resistance (appears after therapy)
What is multidrug resistance? - Answers The development of both resistance and simultaneous cross-
resistance to a wide range of functionally and structurally unrelated chemotherapeutic drugs
What are the two categories for drug resistance? - Answers Intrinsic vs extrinsic
- Intrinsic resistance exists before drug therapy while acquired resistance is induced after therapy
What factors can lead to intrinsic resistance? - Answers -Pre-existing (inherent) mutation that decrease
responsiveness of cancer cells
- heterogeneity of tumors with pre-existing insensitive subpopulation of cells
- activation of intrinsic pathways used as defense against environmental toxins
T/F defective p53 pathway increases resistance to DNA damage agents - Answers T
This is one cause of intrinsic resistance
What transcriptional repressors mediate epithelial-to-mesenchymal transition, making cancer cells more
resistant to treatment? - Answers Snail and Slug
How are cellular detox pathways beneficial to cancer cells? - Answers Although cellular detox pathways
are typically used as a defense agains environmental toxins, they are used by cancer cells to eliminate
cytotoxic effects of anticancer drugs
T/F Mechanisms of acquired drug resistance tend to be similar than those of pre-existing (intrinsic) drug
resistances - Answers False; they tend to be totally different
What factors can acquired resistance be a result of? - Answers -Activation of second (non-targeted)
proto-oncogenes that becomes the newly tumor driver
-mutations or altered expression levels of the drug target
, -changes in tumor microenvironment after treatment
What is considered to be the major reason for chemotherapy resistance? - Answers Elevated efflux of
anticancer agents which result in decreased intracellular drug levels
What is responsible for drug efflux and what superfamily are they from? - Answers Transmembrane
transporters; primarily from the ATP binding cassette (ABC) transporter superfamily.
How many ABC genes does the human body have? - Answers 48 ABC genes that are classified into seven
subfamilies
Which is the most well-characterized ABC transporter? - Answers ABCB1 (MDR1 or P-gp)
What does ABCB1 consist of and what can it do? - Answers ABCB1consists of two transmembrane
domains forming a passage for substrates in addition to two nucleotide binding domains that bind and
hydrolyze ATP. ABCB1 has multiple drug binding sites that can bind and pump a wide variety of
structurally-unrelated drugs from the cell.
T/F ABCB1 can bind and pump a wide variety of structurally-unrelated drugs from the cell - Answers
True, it has multiple drug binding sites
What is commonly seen during application of targeted therapies which block the growth of cancer cells
by inhibiting the activity of specific target proteins involved in tumor development? - Answers What is
frequently seen is alteration of drug targets wither through secondary mutation in the target protein or
by changes in the expression levels due to epigenetic alterations
What is the relationship between lung cancer and secondary resistance? (example with EGFR) - Answers
within 1 year of EGFR inhibitor treatment, 50% of pts develop a T790M mutation on EGFR which leads to
resistance of 1st and 2nd generations of TKIs. There are currently 4 generations on the market to
combat secondary resistance.
What is the relationship between breast cancer and secondary resistance? - Answers Tamoxifen
(compete with estrogen for ligand binding site of ER) resistance develops in pts receiving treatment
(with TX). This led to the development of aromatase inhibitors which interfere with the last step of
estrogen synthesis.
what is the mechanism of action for most chemotherapy drugs? - Answers They kill cancer cells by
inducing DNA damage.
How does the DNA damage response lead to resistance to cancer drugs? - Answers The DNA damage
response (DDR) of affected cells to the anti-cancer drugs may result in reduced efficacy of the drugs by
DNA lesion repairs, leading to drug resistance. Numerous genes involved in DNA repair were found to be
upregulated in 5-FU resistant human colon cancer cell lines. 5-FU treatment induced upregulation of
p53-target genes on DNA damage response and repair. Success to repair the damages led to reduced
cell cycle arrest and apoptosis in the resistant cell lines compared to parental cell lines.
