BIO451 Cancer Biology

Final Project

Case Study:
A 71-year old male seeks attention after developing difficulty and pain during urination. In
addition, the patient complains of intermittent pain in his lower back. His physician performs a
digital rectal exam and notes a lump on the prostate. Blood tests for the prostate specific antigen
(PSA) reveal elevated levels (12ng/ml) of this marker. A transrectal ultrasound is performed,
yielding the results seen in the following image. A biopsy and a full body CT scan were
subsequently performed. The pathology of the biopsy confirmed carcinoma of the prostate.
The CT scan indicated metastases to the bone.

The article Comprehensive Gene Expression Analysis of Prostate Cancer uses gene array
technology to determine the expression levels of genes in prostate cancer. In keeping with the
idea of a more rational form of treatment for cancer, you will propose individualized, targeted
cancer therapies for the treatment of the prostate cancer patient. Assume that the gene array data
detailed in Table 2 of the paper are the data obtained for this patient.

Your task:
Choose 3 targets for therapy considering the gene array data obtained from the patients tumor.
For each target,

1) Explain the role of the target in cancer and its role in normal cells
2) Explain the rationale for choosing the target
3) Propose a means for development of a drug to this target and explain how the drug will work
to affect the target.

Rules of the project:

1. One of your targets must be new (meaning it is not a molecule that we have studied in
class).
2. Choose diverse targets for therapy. Be cognizant of the intricacy of tumor formation: 1)
multi-step tumorigenesis, 2) angiogenesis, 3) metastasis, 4) genome instability, 5)
complexity of tumor structure.
3. For drug development, you need to be aware that certain features of molecules make
them preferred for targeting. You need to weigh these features and indicate how these
affected your decision in the rationale section.
BIO451 Cancer Biology
Final Project

Grading:
Your project will be graded based on the specifications listed below.
Your project and portfolio are due by the beginning of our final exam period in finals week.
Final Project Specifications:
Choice of targets
One of your targets must be new (meaning it is not a molecule that we have studied in class).
Three targets were chosen for therapy.
The 3 targets are diverse in nature (target different mechanisms of cancer).
Targets are chosen from article on gene expression in prostate cancer.

Explain role of target #1 in normal cells

The role of the target in normal cells is described.
The cell signaling processes surrounding the target are discussed.
Specific interactions of the target with other molecules are discussed.
The downstream targets are discussed.
The overall outcome of the pathway discussed.

Explain role of target #1 in cancer

The nature of the change (mutation, LOH, promoter methylation, etc.) leading to cancer is
discussed.
The effect of the change regarding the target is described.
The changes are linked to a facet of cancer (tumorigenesis, angiogenesis, etc.).

Rationale for choosing target #1

The target was chosen for ease of drug design (has catalytic cleft or a specific domain for
protein-protein interactions).
A rationale for this particular target is presented.
Features (positive and negative) of target are outlined.
Broader implications of affecting target on cancer discussed.

Proposal for drug design to affect target #1

A proposal for drug design is presented.
A specific component of the target molecule is specified.
A description of how the component would be disrupted/affected is described.
Discussion of testing of drugs included.

Explain role of target #2 in normal cells

The role of the target in normal cells is described.
The cell signaling processes surrounding the target are discussed.
Specific interactions of the target with other molecules are discussed.
The downstream targets are discussed.
The overall outcome of the pathway discussed.

Explain role of target #2 in cancer

The nature of the change (mutation, LOH, promoter methylation, etc.) leading to cancer is
discussed.
The effect of the change regarding the target is described.
The changes are linked to a facet of cancer (tumorigenesis, angiogenesis, etc.).
BIO451 Cancer Biology
Final Project

Rationale for choosing target #2

The target was chosen for ease of drug design (has catalytic cleft or a specific domain for
protein-protein interactions).
A rationale for this particular target is presented.
Features (positive and negative) of target are outlined.
Broader implications of affecting target on cancer discussed.

Proposal for drug design to affect target #2

A proposal for drug design is presented.
A specific component of the target molecule is specified.
A description of how the component would be disrupted/affected is described.
Discussion of testing of drugs included.

Explain role of target #3 in normal cells

The role of the target in normal cells is described.
The cell signaling processes surrounding the target are discussed.
Specific interactions of the target with other molecules are discussed.
The downstream targets are discussed.
The overall outcome of the pathway discussed.

Explain role of target #3 in cancer

The nature of the change (mutation, LOH, promoter methylation, etc.) leading to cancer is
discussed.
The effect of the change regarding the target is described.
The changes are linked to a facet of cancer (tumorigenesis, angiogenesis, etc.).

Rationale for choosing target #3

The target was chosen for ease of drug design (has catalytic cleft or a specific domain for
protein-protein interactions).
A rationale for this particular target is presented.
Features (positive and negative) of target are outlined.
Broader implications of affecting target on cancer discussed.

Proposal for drug design to affect target #3

A proposal for drug design is presented.
A specific component of the target molecule is specified.
A description of how the component would be disrupted/affected is described.
Discussion of testing of drugs included.

General project requirements

Appropriate biological terminology is used.
Writing is clear and concise.
Proposal is written in an organized and rationale format.