UGR Blog Post 1: Investigation of Combination Treatments in Breast Cancer in Attempt to Overcome Drug Resistance

The title of the research project that Dr. Krucher and I are working on is Investigation of Combination Treatments in Breast Cancer in Attempt to Overcome Drug Resistance. The reason we are investigating combination treatments is because in breast cancer, like in many other cancers, the cancer has the ability to develop resistance to the drugs that are used to attack and kill the cancer cells. This means that after a period of time the drug that was used to treat the cancer is rendered ineffective due to the cancers ability to activate specific resistance pathways and continue proliferating. Therefore, through this research project Dr. Krucher and I plan on determining whether or not combination treatments would be a more effective means at combating this resistance in cancer. From this project I personally expect to learn in a variety of different ways. For example, I plan on learning new laboratory skills and techniques or developing the techniques that I have been taught so far like running a Gel Electrophoresis or Culturing cells or performing Protein Concentration Assays. Furthermore, I also plan on learning how to properly go about conducting research in a laboratory setting.

Our target in this research is the Retinoblastoma (Rb) protein, which is inactivated in almost all cancer types. In cancer cells Rb is highly phosphorylated which inactivates its ability to suppress unwarranted proliferation. The way that Dr. Krucher and I plan on answering these questions is by utilizing a method known as PNUTS (Phosphatase Nuclear Targeting Subunit) knockdown where we reduce PNUTS, a PP1 interacting protein, in cancer cells. PNUTS depletion leads to an activation of PP1 activity which leads to dephosphorylation of the Rb protein, and its activation. We will determine whether PNUTS depletion is a method to suppress cancer drug resistance. We plan on answering this question by continuing to utilize Gel Electrophoresis in order to separate proteins and Western Blot them in order to image them and determine whether or not PNUTS was knocked down. In future experiments we are interested to see if PNUTS Knockdown coupled with other drugs will aid in combating any resistance pathways that certain cancer cells develop.

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