Breast cancer research platform

Project aims/goals​​​

  • ​​​Aim 1: Establish a breast cancer PDO resource platform. Many cancer researchers would greatly benefit from incorporating Patient-Derived-Organoids (PDOs) in their research programs. A major barrier is the expertise required to establish, maintain, and analyze PDOs. We propose to establish a comprehensive breast cancer tumor and PDO resource. This resource will comprise samples from individual breast cancer patients (cohorts), representing all clinical subtypes of ER+/PR+, HER2+, and TNBC. Each cohort will have comprehensive clinical data and will be molecularly profiled with whole genome and whole transcriptome-sequencing through the MOHCCN initiative. PDOs will be generated for each cohort and similarly molecularly characterized. This comprehensive tumor/PDO resource will be a powerful tool for our cancer research community.
  • Aim 2: Investigate mechanisms of therapy resistance. PDOs are unique patient-centric living model systems with exceptional experimental potential. Our team will utilize the breast cancer PDO platform to address critical knowledge gaps. For example, we will identify targetable drivers of disease for the most lethal subtype; triple negative breast cancer (TNBC). Genomic/transcriptomic analyses from tumors will reveal driver gene aberrations and expression alterations to identify druggable targets. Pharmacological screening of the matched PDO will functionally test drug response specific to the individual patient. This work could advance the utility of PDOs for treatment decision-making.  
  • ​Aim 3: Support multidisciplinary programs to advance breast cancer research. The research potential of this PDO biobank platform will be expanded by collaborations throughout our innovative and multidisciplinary research networks. MOHCCN infrastructure will facilitate data sharing of molecular and clinical information for cohort tumor samples. Our research group will establish a democratic process for sharing of the matched PDOs, while concurrently providing expert advice. The outcome will be expanded multidisciplinary clinical, basic, and analytical research. ​​

Summary

​​Breast cancer is the most diagnosed cancer in women. Treatment decisions are typically based on the combination of hormone receptor (ER/PR) and HER2 status of the primary tumor at diagnosis. In addition to surgery and radiation, treatment can entail a diverse regimen of chemotherapy, hormone therapy, targeted molecular therapy, and immunotherapy. A priori, there is no reliable way to know how a patient will respond to a given regimen. Patient-Derived-Organoids (PDOs) have emerged as powerful tools to potentially overcome this roadblock to personalized medicine. In this system, patient tumors are propagated as three-dimensional (3D) organoids embedded within an extracellular matrix such that they retain the morphological, histological, genomic, and transcriptomic signatures of the original tumor. Critically, they can be expanded and tested, are stable over time, and can be frozen and revived for long-term studies. These living ‘avatars’ are rapidly revealing insights into the hidden nature of tumor cell behavior and have the potential to predict treatment response. Our goal is to establish a biobank of patient tumors with matched PDOs (aim 1) that will address critical knowledge gaps in breast cancer pathobiology (aim 2) and boost multidisciplinary breast cancer research with the potential to advance personalized medicine (aim 3).​ 

Anticipated outcomes and impact​​

​​We propose to establish a multidimensional platform for matched breast cancer tumors and Patient-Derived-Organoids (PDOs) that will be deeply characterized at the clinical, histopathological, and molecular levels. This platform will generate state-or-the-art data and provide critical tools for the breast cancer research community with the potential to become directly relevant to people facing cancer. Discoveries may reveal novel treatment approaches that can be tested on matched PDOs and may contribute to personalized medicine in the future.​ 

Key Researchers