Cell cycle plasticity underlies fractional resistance to palbociclib in ER+/HER2- breast tumor cells.

The CDK4/6 inhibitor palbociclib blocks cell cycle progression in Estrogen receptor-positive, human epidermal growth factor 2 receptor-negative (ER+/HER2-) breast tumor cells. Despite the drug's success in improving patient outcomes, a small percentage of tumor cells continues to divide in the presence of palbociclib-a phenomenon we refer to as fractional resistance. It is critical to understand the cellular mechanisms underlying fractional resistance because the precise percentage of resistant cells in patient tissue is a strong predictor of clinical outcomes.

Tamoxifen Response at Single-Cell Resolution in Estrogen Receptor-Positive Primary Human Breast Tumors.

Purpose: In estrogen receptor-positive (ER+)/HER2- breast cancer, multiple measures of intratumor heterogeneity are associated with a worse response to endocrine therapy. We sought to develop a novel experimental model to measure heterogeneity in response to tamoxifen treatment in primary breast tumors.

Experimental Design: To investigate heterogeneity in response to treatment, we developed an operating room-to-laboratory pipeline for the collection of live normal breast specimens and human tumors immediately after surgical resection for processing into single-cell workflows for experimentation and genomic analyses.

Using Community-Based Participatory Research to Conduct a Collaborative Needs Assessment of Mental Health Service Users: Identifying Research Questions and Building Academic-Community Trust.

Attempts to meaningfully engage people with serious mental illnesses (SMI) as allies in conducting research have often failed because researchers tend to decide on the research topic without including community members. Academic researchers can avoid this pitfall by collaborating with community members to conduct a needs assessment to identify relevant research topics and build trust. Here, we report on the results of a psychosocial needs assessment for adult mental health service users in Massachusetts conducted by an academic-peer research team.

Tamoxifen Response at Single Cell Resolution in Estrogen Receptor-Positive Primary Human Breast Tumors.

In ER+/HER2- breast cancer, multiple measures of intra-tumor heterogeneity are associated with worse response to endocrine therapy. To investigate heterogeneity in response to treatment, we developed an operating room-to-laboratory pipeline for the collection of live human tumors and normal breast specimens immediately after surgical resection for processing into single-cell workflows for experimentation and genomic analyses. We demonstrate differences in tamoxifen response by cell type and identify distinctly responsive and resistant subpopulations within the malignant cell compartment of human tumors.

High expression of the RET receptor tyrosine kinase and its ligand GDNF identifies a high-risk subset of estrogen receptor positive breast cancer.

Purpose: Resistance to endocrine therapy is the primary cause of treatment failure and death in patients with ER-positive (ER +)/luminal breast cancer. Expression and activation of the RET receptor tyrosine kinase may be driving poor outcomes. We aim to identify high-risk patients and druggable pathways for biomarker-based clinical trials.