NCI Workshop on Lineage Plasticity and Androgen Receptor–Independent Prostate Cancer

The National Cancer Institute organized a Workshop on Lineage Plasticity and Androgen Receptor-Independent Prostate Cancer in a joint effort by the NCI’s Division of Cancer Treatment and Diagnosis, Division of Cancer Biology, Center for Cancer Research, Coordinating Center for Clinical Trials, together with investigators of the NCI SPOREs in Prostate Cancer and the Prostate Cancer Task Force of the NCI Genitourinary Steering Committee. This workshop occurred on December 6-7, 2018 at the NIH Main Campus in Bethesda, MD and was chaired by Drs. Himisha Beltran, Bill Dahut, and Peter Nelson. The meeting assembled leaders in the field to share scientific insights and identify emerging opportunities in basic, translational, and clinical research (agenda).

Workshop Goals

Advance the state-of-the-science to address the following crucial needs:

• Fundamental understanding of how lineage plasticity occurs
• Determination of the temporal contribution and cooperation of emerging drivers
• Development of preclinical models that recapitulate the biology of the disease and the recognized phenotypes
• Identification of therapeutic targets and novel trial designs dedicated to the entity as it is defined

 

 

Workshop Highlights

• Scientists and clinicians focused on enhancing knowledge of the fundamental role of lineage plasticity in driving the progression of multiple cancer subtypes and in impacting treatment response.
• Four working groups tackled molecular, preclinical, and clinical aspects of this continuum.
• Experts who are investigating the role of lineage plasticity in other cancer types provided their knowledge and experience.
• Scientific sessions covered the scope of the problem and the cellular and molecular biology of androgen receptor-independent prostate cancer, and attendees discussed translational strategies to advance basic discoveries into the clinic.

Workshop Outcomes and Potential Deliverables

• Identification of major gaps of knowledge in the field
• Generation of novel ideas on how to address the scientific and clinical challenges

• The following two focus groups will organize the next steps of this endeavor:

  1. The basic biology of Rb loss in small cell/neuroendocrine prostate cancer (NEPC), small cell lung cancer, and other small cell carcinomas
     • Attempt to better define the method of loss (e.g., deletion, phosphorylation) and the impact of co-occurring alterations (e.g., TP53)
     • Explore collaborative ideas to improve knowledge of the clinical, pathologic, and molecular features underlying Rb deficient tumors
     • Discuss strategies for model development and drug discovery (e.g., CRISPR)
       
       
  2. Imaging capabilities to accelerate clinical translation of emerging data in this field
     • Discuss strategies for using prostate-specific membrane antigen or dihydrotestosterone positron emission tomography (PET) combined with fluorodeoxyglucose PET imaging as a non-invasive means to detect androgen receptor signaling heterogeneity and lineage plasticity
     • Utilize these data, in combination with clinical and molecular features, to develop a working definition of lineage plasticity for future therapeutic trials

The scientific expertise, dedication, and genuine passion of the late Andrew Hruszkewycz, MD, PhD were instrumental in the success of this workshop.

 

 

(L to R): Peter Nelson, MD, Fred Hutchinson Cancer Center and Andrew Hruszkewycz, MD, PhD, DCTD