Evaluating the Role of Cathepsin Inhibition in Chemotherapy Resistant Osteosarcoma

Payton Bogert

Authors: Payton Bogert, Henrietta Fasanya, Dietmar Siemann Ph.D

Faculty Mentor: Dr. Siemann Dietmar

College:  College of Medicine

Abstract

Osteosarcoma (OS) is the most common primary bone cancer predominantly occurring in pediatric patients. Cancer metastasis is the leading cause of cancer related deaths. Over 80% of patients who present with OS will develop metastasis. A key factor in the metastatic process is the presence of proteases that contribute to the development of a vascular network, degrade the extracellular matrix, and increase the cell’s ability to invade. Our project focuses on a family of proteases called cathepsins. Specifically, we are interested in Cathepsin L (CTSL) and Cathepsin K (CTSK). In addition to their roles in metastasis, recent studies have demonstrated that cathepsins play a role in cancer cell resistance to chemotherapy. Our studies evaluate the role of cathepsins on the development of doxorubicin resistance in vitro. We utilized the invasion and migration chamber assay and clonogenic cell survival to assess cell migration, invasion, and cell survival. We have developed a doxorubicin resistant cell line murine cell line DoxR-K7M2 to analyze the effect of CTSL/CTSK inhibition via KGP94 on cell viability and metastatic phenotype. We hypothesize that cathepsin inhibition may be a promising strategy to increase the efficacy of current chemotherapeutics in drug resistant cells and improve overall survival for OS patients.

Poster Pitch

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Poster

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9 Responses
  1. Grethel Aguila

    Great job, Payton! Your study is complex but interesting. I like the graphical abstract – it shows the process in a way that is easy to visualize.

  2. Hey Payton! Great job presenting! I really liked your project and was very impressed. Pretty exciting to see that targeting cathepsins may have potential for decreasing chemotherapeutic resistance. I was wondering if your lab has studied these effects in any other cancer types/cell lines? (given that chemotherapeutic resistance is a prevalent issue across the spectrum of cancer)

    1. Payton

      Unfortunately, we have not had the chance to study this but hopefully this is something we can look into in the future!

      1. Got it, thank you! Also I want to add that it has been a pleasure getting to know you and learn with you as a part of the UFHCC USP cohort! I wish you the best in yours future endeavors!