One Tablet a Day May Keep Cancer Away

By Adam J. Kleinschmit

Abstract

This dilemma/decision case study is intended to demonstrate how knowledge of signal transduction pathways can be applied to the pharmaceutical industry and within a medical setting. The case scenario revolves around a physician scientist's analysis of a chronic myelogenous leukemia (CML) patient's resistance to the cancer drug Gleevec® (imatinib). Students explore the molecular targets of drugs that inhibit cell signaling, while considering the best course of treatment for the medical patient. Written for an undergraduate sophomore level cell biology course, the case is also suitable for general biology, genetics, molecular biology, pharmacology, and cancer biology.

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Date Posted

03/15/2016

Overview

Objectives

Explain the genetic basis for chronic myelogenous leukemia (CML).
Sketch a generic receptor tyrosine kinase signal transduction pathway and identify potential drug targets within the pathway.
Recognize and articulate potential tradeoffs when considering different options for a patient medical CML treatment plan.
Evaluate a complete blood count and compare and contrast the phenotype of a CML patient's blood smear to that of a control.
Interpret a karyotype from an individual with a chromosomal translocation.
Explain the molecular steps involved in converting mRNA into cDNA with reverse transcriptase and describe how the resulting cDNA can be used to quantitate transcript levels via qPCR.
Compare and contrast a proto-oncogene with an oncogene.
Illustrate how the cancer drug Gleevec works at the molecular level.
Assess alternative drug targets in a generic receptor tyrosine kinase signal transduction pathway for their potential effectiveness in CML cell specific apoptosis.
Formulate a testable hypothesis on how CML relapse may arise independent of Gleevec resistance.
Propose a solution for a medical dilemma faced by a physician in the treatment of a patient displaying symptoms of a CML relapse.

Keywords

Cancer; leukemia; Gleevec; imatinib; PCR; karyotype; pharmaceutical; bone marrow transplant; signal transduction pathway; drug targets; cell signaling; protein kinase; phosphorylation cascade; receptor

Subject Headings

Biology (General)

Cell Biology

Genetics / Heredity

Molecular Biology

Pharmacy / Pharmacology

EDUCATIONAL LEVEL

Undergraduate lower division, Undergraduate upper division

FORMAT

PDF

TOPICAL AREAS

N/A

LANGUAGE

English

TYPE/METHODS

Directed, Discussion

Teaching Notes & Answer Key

Teaching Notes

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Answer Key

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Materials & Media

Supplemental Materials

The following supplemental materials can be used with this case study:

Videos

Animation: Gleevec
This animation shows how the drug Gleevec is designed to interfere with the stimulation of growth in leukemia cells. Running time: 1:04 min. Produced by HHMI BioInteractive.
Animation: Gleevec-Resistant Form of Kinase BCR-ABL
This animation describes the mechanism of the drug, dasatinib. Dasatinib is used to treat Gleevec resistant CML. Running time: 2:14 min. Produced by HHMI BioInteractive.
Animation: Gleevec Inhibits Cancer-Causing Kinase BCR-ABL
This animation explains the mechanism of the the drug Gleevec and how it binds to and inactivates BCR-ABL, a mutant kinase that causes chronic myeloid leukemia. Running time: 3:31 min. Produced by HHMI BioInteractive.
Animated Tutorial: BCR-ABL: Cancer Protein Structure and Function
This self-paced animated tutorial (Click and Learn) supports the 2013 Holiday Lectures on Science and describes how understanding the structure of the BCR-ABL kinase led to the development of an effective treatment for chronic myeloid leukemia. It provides an example of how advances in molecular biology, structural biology, and DNA sequencing have revolutionized the treatment of certain types of cancer. Produced by HHMI BioInteractive.
Lecture: Cancer As a Genetic Disease
Lecture from the 2013 HHMI Holiday Lecture Series. Dr. Sawyers presents an overview of cancer biology and describes how understanding the molecular mechanisms involved in a type of cancer, chronic myeloid leukemia, resulted in the development of Gleevec, one of the first targeted cancer drugs. Running time: 58:33 min. Produced by HHMI BioInteractive.