Cancer Drug Resistance| EXAM QUESTIONS WITH
COMPLETE SOLUTIONS (ANSWERS VERIFIED 100%
CORRECT)
What transcriptional repressors mediate epithelial-to-mesenchymal transition, making
cancer cells more resistant to treatment? - ✔✔Snail and Slug
How are cellular detox pathways beneficial to cancer cells? - ✔✔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 - ✔✔False; they tend to be totally different
What factors can acquired resistance be a result of? - ✔✔-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? -
✔✔Elevated efflux of anticancer agents which result in decreased intracellular drug
levels
What is responsible for drug efflux and what superfamily are they from? -
✔✔Transmembrane transporters; primarily from the ATP binding cassette (ABC)
transporter superfamily.
, How many ABC genes does the human body have? - ✔✔48 ABC genes that are
classified into seven subfamilies
Which is the most well-characterized ABC transporter? - ✔✔ABCB1 (MDR1 or P-gp)
What does ABCB1 consist of and what can it do? - ✔✔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 - ✔✔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? - ✔✔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) - ✔✔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? -
✔✔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.
COMPLETE SOLUTIONS (ANSWERS VERIFIED 100%
CORRECT)
What transcriptional repressors mediate epithelial-to-mesenchymal transition, making
cancer cells more resistant to treatment? - ✔✔Snail and Slug
How are cellular detox pathways beneficial to cancer cells? - ✔✔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 - ✔✔False; they tend to be totally different
What factors can acquired resistance be a result of? - ✔✔-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? -
✔✔Elevated efflux of anticancer agents which result in decreased intracellular drug
levels
What is responsible for drug efflux and what superfamily are they from? -
✔✔Transmembrane transporters; primarily from the ATP binding cassette (ABC)
transporter superfamily.
, How many ABC genes does the human body have? - ✔✔48 ABC genes that are
classified into seven subfamilies
Which is the most well-characterized ABC transporter? - ✔✔ABCB1 (MDR1 or P-gp)
What does ABCB1 consist of and what can it do? - ✔✔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 - ✔✔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? - ✔✔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) - ✔✔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? -
✔✔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.
