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Targeting CaSR/GABAB R1 Heterodimers to Treat Bone Metastases in Breast Cancer

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Technical Report,01 Sep 2017,31 Aug 2018

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Yale University New Haven United States

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The goal of this project is to test whether genetic or pharmacologic inhibition of CaSRGABAB R1 heterodimers canantagonize the growth andor survival of breast cancer cells exposed to high extracellular calcium in vitro or grown in animalmodels of bone metastases in vivo. Progress was slowed this past year due to change in personnel. Dr. Kim left to take afaculty position in South Korea and, after an interval of several months, we hired Dr. Julie Hens to take Dr. Kims place. Dr.Hens is an accomplished researcher with experience in developmental and cancer biology. She is in the process of developingtetracycline-regulated GABAB R1-knockdown cell lines to circumvent the cell death caused by stable chronic knockdown celllines to study the effects of loss of GABB R1 on cAMP production, PTHrP expression and cell proliferation and apoptosis.She has validated that the blocking the CaSR with NPS2143 synergizes to increase cell death caused by a DNA damagingagent, MNNG and is now examining whether this agent will sensitize to radiation damage or platinum-based chemotherapy.Finally, she is begging to study the effects of NPS2143 on the growth of breast cancer cells in bone in vivo.

Subject Categories:

  • Medicine and Medical Research
  • Medicine and Medical Research

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