You are leading a team of researchers at a pharmaceutical company. Your goal is to design drugs that help fight cancer. Specifically, you want to focus on drugs that bind to and inactivate certain proteins, thereby halting cell cycle progression. One of your team members suggests targeting the retinoblastoma (Rb) protein and inhibiting this protein. Will this approach be successful? Why or why not?

Question

A.  This approach will not be successful. Rb is tumor-suppressor protein, and functions to inhibit the action of a number of cell cycle regulatory proteins. A drug designed to inactivate the Rb protein would essentially create the same situation as in as a cell that lacks both copies of the Rb gene. Lack of Rb activity would release the inhibition of cell cycle regulatory proteins, thereby promoting cell cycle progression, rather than halting it.
B.  This approach will be successful. Rb is an oncogene, and functions to activate a number of cell cycle regulatory proteins. A drug designed to inactivate the Rb protein would halt the cell cycle in cells that contain an active Rb.  As a result, cancer cells expressing a constitutively active Rb protein would be good targets for this type of therapeutic.
C.  This approach will be successful. Rb is tumor-suppressor protein, and functions to inhibit the action of a number of cell cycle regulatory proteins. A drug designed to inactivate the Rb protein would activate cell cycle inhibition. Lack of Rb activity would therefore inhibit the cell cycle regulatory proteins.
D.  This approach will not be successful.  Rb is an oncogene, and functions to activate a number of cell cycle regulatory proteins.  A drug designed to inactivate the Rb protein would actually activate cell cycle progression.  As a result, this drug would likely make this situation worse for patients whose cancer cells contain mutant Rb.

Clarify Question
  · What is the key concept addressed by the question?
· What type of thinking is required?
· What key words does the question contain and what do they mean?
  Gather Content
  · What do you know about Rb? How does it relate to the question?
  Consider Possibilities  
  · What other information is related to the question? Which information is most useful?
  Choose Answer
  · Given what you now know, what information and/or problem solving approach is most likely to produce the correct answer?
  Reflect on Process
  · Did your problem-solving process lead you to the correct answer? If not, where did the process break down or lead you astray? How can you revise your approach to produce a more desirable result?

Answer 1

A.  This approach will not be successful. Rb is tumor-suppressor protein, and functions to inhibit the action of a number of cell cycle regulatory proteins. A drug designed to inactivate the Rb protein would essentially create the same situation as in as a cell that lacks both copies of the Rb gene. Lack of Rb activity would release the inhibition of cell cycle regulatory proteins, thereby promoting cell cycle progression, rather than halting it.

Clarify Question
  · What is the key concept addressed by the question?
        o The question asks about the role of Rb in regulating the cell cycle.
· What type of thinking is required?
        o You are being asked to analyze statements about the benefits of inhibiting Rb as a cancer therapy.
· What key words does the question contain and what do they mean?
        o Rb – this protein is a tumor suppressor, it normally halts the cell cycle.
        o Halting cell cycle progression – many drugs used to treat cancer do so by slowing down the cell cycle.
  Gather Content
  · What do you know about Rb? How does it relate to the question?
        o Rb is a tumor suppressor that halts the cell cycle.  Mutations that block Rb activity lead to an increase in the cell cycle and possibly cancer.
  Consider Possibilities  
  · What other information is related to the question? Which information is most useful?
        o Rb is not an oncogene, it is a tumor suppressor.
        o The researchers propose to inhibit the tumor suppressor Rb, this would have the same effect as mutations in Rb that lead to cancer.
  Choose Answer
  · Given what you now know, what information and/or problem solving approach is most likely to produce the correct answer?
        o The best answer is that this experiment would not be successful, because Rb is a tumor suppressor you do not want not inactivate it to prevent cancer.
  Reflect on Process
  · Did your problem-solving process lead you to the correct answer? If not, where did the process break down or lead you astray? How can you revise your approach to produce a more desirable result?
        o This question asked you to analyze several statements to see which best explains if an experiment would work. If you got the correct answer, great job! If you got an incorrect answer, where did the process break down? Did you recall that Rb was a tumor suppressor?  Did you realize that inhibiting a tumor suppressor would actually increase the risk of cancer?