Breast Cancer Translational Research Group (BCTRG)

Congratulations to our post-doctoral fellows who won two of eight Young Investigator Awards from the ECOG-ACRIN Cancer Research Group! Drs. Kiani and Bagheri were invited to give oral presentations in Washington DC on “Development of a semi-automated H-score for digital pathology image analysis” and “Surgical innovation to improve take rate of PDX generation from primary breast tumors”.

[¹⁸F]FluorThanatrace Maximum Standardized Uptake Value (SUV) vs Tumor Subtype (JAMA Oncol. 2020;6(6):921-923)

The Breast Cancer Translational Research Group (BCTRG) is a highly collaborative multi-disciplinary team involving scientific interactions across several departments, programs, and schools at Penn including Radiochemistry, Oncology, Surgery, Chemistry, Pathology, Cancer Biology, and Biostatistics. Our group also works closely with the Breast Cancer Molecular Imaging Group and Penn Center for Genome Integrity.

Mission

The Breast Cancer Translational Research Group, led by Elizabeth McDonald, MD, PhD and Sarah Gitto, PhD, has a two pronged mission of enabling precision cancer care and training the next generation of breast cancer researchers.  

1. Our primary research focus is understanding why some breast cancers are resistant to current therapies and developing functional imaging markers to predict and monitor therapy response.
2. We prioritize mentoring junior investigators in the scientific method with projects geared toward every level–undergraduates, medical students, graduate students, residents and post-doctoral fellows. We welcome inquiries about how to get involved in breast cancer research. As part of our commitment to the local community, we partner with Women's Campaign International to introduce Philadelphia high school students to academic careers.
3. BCTRG is also committed to inclusive excellence in research and we participate in mentoring through the RISE (Radiology Initiative to Support Inclusive Excellence in Research) program, which Dr. McDonald co-directs.

Research

There are numerous projects for trainees including residents and graduate students. Prior bench research experience is not required. Our lab research is divided into three teams representing unique areas of expertise:

• Breast Cancer PDX Program (Team Leader, Tony Secreto, MRA)
• Artificial Intelligence and Data Science (Team Leader, Sina Bagheri, MD)
• Molecular Integrated Diagnostics (Team Leader, Mahsa Kiani, MD)

Additionally, the Molecular Radiopharmacology and Cytology Lab is a departmental resource staffed by members of BCTRG providing services to the research community including microscope training, tissue staining, help with cell culture, assistance structuring imaging protocols/clinical trials to incorporate relevant biomarker discovery and concurrent companion diagnostic development, assistance with writing statement of work (SOW) for tissue acquisition and storage.  Ola Sharaff is the senior scientist/lab manager and point of contact for that lab.

DNA repair and mechanisms of cancer drug efficacy 

Our bench to bedside research program aims to understand differences in cancer DNA repair mechanisms and develop predictive biomarkers for targeted therapy response.

Disparate clinical outcomes occur in women who have breast cancer and similar tumor size, molecular subtype, histology, and even given similar age or genetic mutation status. Our research interrogates differential tumor DNA repair capability as a cause for heterogeneous clinical responses, specifically focusing on PARP-1 expression, the target of PARP inhibitors and a key component of every aspect of DNA repair. To this end, the laboratory supports tissue analysis for two ongoing clinical trials in patients with breast cancer that correlate chemotherapy or PARP inhibitor response to a tumor’s ability to repair DNA.

A recent multidisciplinary collaboration involving our lab, the Breast Cancer Molecular Imaging Group and the Maxwell Lab demonstrated that in vivo breast cancer PARP-1 expression can be accurately measured through a non-invasive imaging test and widely varies among different breast cancer subtypes. The work (JAMA Oncol. 2020;6(6):921-923) has an Altmetric score of 29, ranking it among the top 5% of all research published internationally.

Additional work resulting from our collaborative efforts with the Breast Cancer Molecular Imaging Group and the Department of Pathology demonstrated that proliferation can be measured by a probe directed at the sigma-2 receptor complex (J Nucl Med. 2020 May;61(5):665-670). 

PDX resource and pharmacodynamics experiments

As a companion to this work, collaborating with the Stem Cell and Xenograft core, our laboratory has built a library of patient-derived xenografts (PDX) with the goal of elucidating specific changes in DNA repair that impact tumor response. The models are also used in collaboration with other labs, such as Dr. Ben Black’s lab in the Department of Biochemistry and Biophysics and the Britton Chance Laboratory of Redox Imaging. The ultimate goal of our research is to design personalized interventions if less than complete therapy response is predicted, or has already occurred. 

The PDX resource is supported by the PennRad Biobank, a joint effort between our lab and the Department of Pathology.  The biobank is unique resource providing tissue for breast cancer research with full characterization of collection parameters and molecular characterization.

Molecular Radiopharmacology and Cytology Resource Laboratory

In vivo Small Animal Imaging

• PET, SPECT, CT, MR small animal imaging
• Dedicated state-of-the art instrumentation
• Serial imaging, dynamic imaging, multi-tracer imaging, multi-modal imaging
• Consultation &, experimental design
• Protocols, logistics & study cost-estimates

Image-based Informatics

• Hi-spec workstations for analysis
• Current analysis software packages
• Multimodal Image registration
• Non-invasive image segmentation
• ROI/VOi delineation, PK,PD analysis

Ex vivo tissue assay

• Tissue harvesting, embedding, cryosectioning
• Autoradiography: tissue distribution, ligand binding
• Histological and Immunostaining
• Pixel-based multimodal correlation
• Expertise in imaging Far-Red and NIR dyes
• Slide scanning: up to x40 air, xl00 oil

Community Engagement

The BCTRG is committed to reducing care disparities in our community.  We have partnered with the Chrysalis Initiative to increase clinical trial enrollment and provide support for all women and especially Black women and other women of color who are impacted by breast cancer.  To access this resource please click here: The Chrysalis Initiative/BC NAVI App