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2021 Michael and Patricia Berns-PCF Young Investigator Award

Investigating the Polyaneuploid Transition as a Mechanism of Therapy Resistance in Distant Site Metastases

George Butler, PhD
Johns Hopkins University

Mentor: Kenneth Pienta, MD

Description:

  • Polyaneuploid cancer cells (PACC) are a recently discovered cancer cell state, where giant cancer cells with either enlarged or multiple nuclei form under stress. PACCs are more resistant to cancer treatment and may be the cause of treatment resistance and cancer recurrence.
  • Dr. George Butler is investigating the biology of PACCs in prostate cancer.
  • In this project, Dr. Butler will use new genetic lineage tracing and time-lapse imaging technologies to map cancer cells as they transition through the PACC state in response to therapy. Whether non-PACC cancer cells that are derived from PACCs have a “memory” that confers therapy resistance will be investigated.
  • Molecular profiles will be obtained from PACCs throughout these transitions, and investigated to identify vulnerabilities that may be targeted by new treatments.
  • Novel therapeutic strategies that sequence standard chemotherapy followed by treatments that target PACC transition states will be tested in preclinical models.
  • If successful, this project will determine the role and biology of PACCs in treatment resistance and cancer progression, and identify targetable vulnerabilities of PACCs that can be used as new treatments to prevent the emergence of resistance to standard cancer therapies.

What this means to patients: Polyaneuploid cancer cells (PACC) are a recently discovered cancer cell state that may enable therapeutic resistance and cancer recurrence. Dr. Butler will study the biology of PACCs and determine ways to therapeutically target them, in order to prevent cancer from recurring after standard therapies.