Document Type

Honors Capstone Project

Date of Submission

Spring 5-1-2012

Capstone Advisor

Sandra G. Hudson

Honors Reader

Thomas P Fondy

Capstone Major

Biology

Capstone College

Arts and Science

Audio/Visual Component

no

Capstone Prize Winner

no

Won Capstone Funding

yes

Honors Categories

Sciences and Engineering

Subject Categories

Biology | Cancer Biology | Cell Biology

Abstract

Cancer is a group of diseases characterized by abnormal control of cell growth and cell survival. Current treatment for cancer employs a combination of modalities including surgery, radiation, chemotherapeutic drugs, and immunotherapy. Our lab focuses on personalized medicine and treatments that can specifically target molecular features of a tumor as presented by the particular patient being treated. Cancers often exhibit an over-expression or under-expression of certain proteins that play a large role in regulating the process of apoptosis, which is programmed cell death. This study focuses on proposing drug treatment for cancer that is personalized in that it targets a protein family that is often over-expressed. This study was conducted on four human breast cancer lines: MDA-468, MDA-231, BT-20 and T47D. The protein family studied was the BCL-2 family member proteins which are divided in pro- and anti- apoptotic proteins. Two of the four cell lines were characterized by an over-expression of anti-apoptotic proteins which offers an option for specific targeted treatment by invoking inhibition of the over-expressed proteins. A small molecule BCL-2 inhibitor, Obatoclax (GX15-070) was used in this study in combination with radiation therapy to observe the effects on growth of these cancerous cells and to determine whether apoptosis was induced. This study shows that Obatoclax and radiation in combination is more effective inducing apoptosis in neoplastic cells lines that over-express anti-apoptotic BCL-2 family members. This finding is significant because it demonstrates the potential value of personalized, specific targeted treatment. Not all tumors have an over-expression of anti-apoptotic BCL-2 family members, therefore Obatoclax would not be an effective treatment for such cancers. Since this drug would be most effective in treating tumors with an over-expression of anti-apoptotic BCL-2 family members, this study proposes a method to discover which tumors may over-express anti-apoptotic BCL-2 family members and allows for quantification. This allows for the specific personalized treatment of certain cancers and may be a more effective approach to treatment than just the standard treatment options.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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