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One Tablet a Day May Keep Cancer Away



Author:

Adam J. Kleinshmit
Department of Biology and Earth Sciences
Adams State University
akleinschmit@adams.edu

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.

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
Topical Area: N/A
Educational Level: Undergraduate lower division, Undergraduate upper division
Formats: PDF
Type/Method: Directed, Discussion
Language: English
Subject Headings: Biology (General)   Cell Biology   Genetics / Heredity   Pharmacy / Pharmacology   Molecular Biology  
Date Posted: 3/15/2016
Date Modified: N/A
Copyright: Copyright held by the National Center for Case Study Teaching in Science, University at Buffalo, State University of New York. Please see our usage guidelines, which outline our policy concerning permissible reproduction of this work.

Teaching Notes


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Answer Key


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Supplemental Materials


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

  Data Points Activity: Efficacy of a Treatment for Chronic Myeloid Leukemia hhmi/
This figure and activity depicts data from Dr. Brian Druker and colleagues monitoring of white blood cell counts in six patients with chronic myeloid leukemia treated with the drug, STI571, which blocks the activity of the cancer-causing tyrosine kinase BCR-ABL. Each patient (denoted by a different colored line) received 500 mg of STI571 per day for 150 days. The dotted line represents the upper limit of the normal white blood cell count range. Download the educator guide PDF, which includes questions to guide a class discussion on the graph characteristics and what the data show.
  3D Model Print File for Gleevec-resistant BCR-ABL, a mutated form of ABL Kinase hhmi/

  3D Model Print File for Dasatinib, a drug that can inhibit BCR-ABL and Gleevec-resistant BCR-ABL hhmi/

  3D Model Print File for BCR-ABL, an unregulated kinase that causes cancer hhmi/

  3D Model Print File for Imatinib (Gleevec), a drug that mimics ATP and inhibits BCR-ABL hhmi/

  3D Model Print File for Adenosine Triphosphate (ATP) hhmi/

Videos

The following video(s) are recommended for use in association with this case study.

  Animation: Gleevec hhmi/
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 hhmi/
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 hhmi/
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 hhmi/
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 hhmi/
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.




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