Walther Cancer Foundation and Notre Dame Benefactors
Endow Cancer Cure Ventures Program

Effective eradication of cancer calls for a spectrum of approaches along the basic to clinical research continuum to develop an understanding of how to detect cancers in early stages, how tumors progress and metastasize, and how to treat primary, metastatic and recurrent disease. Research at the Harper Cancer Research Institute (HCRI) is predominantly focused on the basic and pre-clinical end of this research spectrum. From inception, the HCRI was intentionally designed to bring together researchers and trainees from distinct disciplines in the biological, chemical, physical, engineering, and medical sciences to address cancer-specific problems. The focused intersection of the tools, training, and approaches employed by interdisciplinary teams represents a unique and largely untapped resource for discovery and innovation.

The HCRI research model is well-aligned with the National Academies’ focus on interdisciplinary research as “a mode of research by teams or individuals that integrates information, data, techniques, tools, perspectives, concepts, and/or theories from two or more disciplines or bodies of specialized knowledge to advance fundamental understanding or to solve problems whose solutions are beyond the scope of a single discipline or area of research practice" [1]. This concept is echoed by the National Cancer Institute’s Collaboration and Team Science Field Guide [2], which concludes “Innovations and advances not possible within one laboratory are emerging from collaborations and research teams that have harnessed techniques, approaches, and perspectives from multiple scientific disciplines and therapeutic areas.” Thus, the HCRI is strongly positioned to conduct cancer-focused convergence research, defined by the National Science Foundation as research conducted within a paradigm that “builds upon transdisciplinary approaches to research by intentionally bringing together intellectually diverse scientists and engineers at a project's inception in new collaborations that can generate multiple solutions to complex problems” [3]. 

Productive convergence research teams do not just self-assemble! A high activation energy is often required, resulting from discipline-specific differences in terminology and jargon and an incomplete understanding among team members of both the most relevant cancer research problems and accessible technical innovations.  Significant effort is required from all team members to effectively “translate” their ideas to other members of the team. To incentivize cancer-focused convergence research, we created the Cancer Cure Ventures (CCV) program in 2011.  The overall goal of the CCV program is to stimulate interdisciplinary cancer research among HCRI scientists in diverse disciplines by promoting novel integrative interactions between research groups from distinct scientific fields. With generous support from the Walther Cancer Foundation, sizeable seed grants have been awarded on a competitive annual basis to interdisciplinary teams of researchers. By encompassing joint mentoring of a post-doctoral scholar as the functional interface between the laboratory teams, and requiring a clearly defined set of metric-driven deliverables, the CCV program has been extraordinarily successful. Data collected over the time span of 2012-2020 show a return on investment of $12 of peer-reviewed extramural research support returned to Notre Dame for every $1 invested by the CCV program.

More impressive than the extramural funding metrics are the projects themselves. With CCV support, we have

• opened a window to understanding breast cancer metastasis to the brain and the complex, yet targetable, interactions of breast cancer cells with resident brain cells in this unique microenvironment  [4] 
• shown that mechanically activated bones can survive in long-term culture, providing a model for discovery of molecules regulating dormancy of bone-metastatic tumor cells [5] 
• engineered new models of matrix stiffness that are being applied to identify molecular changes influencing breast cancer progression, particularly in the context of aging [6]
• discovered that disease-specific mechanical forces tune ovarian cancer cells to a more aggressive phenotype and provide a novel means of tumor-host communication through tunneling nanotubes that may promote tumor survival [7]
• developed nanomembrane-based microfluidic devices for detection and isolation of extracellular vesicles and identification of specific nucleic acid ‘signatures’ for early cancer detection and monitoring of disease recurrence [8]

These projects enable us to confront cancer in a whole new way, enhanced by the perspectives and tools from many disciplines. Importantly, the CCV program motivates engineers and scientists, who may otherwise pursue alternative areas of investigation, to focus their intellectual efforts on cancer-specific research questions. Our goal is to translate these innovative discoveries into improved patient outcomes.

Given the success of this program we are delighted to announce that the Walther Cancer Foundation, together with a group of generous Notre Dame benefactors, have established a $10 million endowment to support the CCV program and associated training programs in perpetuity. Both Tom Grein, the Foundation’s President and CEO and Craig Brater, Walther’s Vice President of Programs, expressed their pleasure in seeing Notre Dame achieve this major milestone in building a sustainable research and training endowment for the HCRI.  Brater remarked that “the Walther Cancer Foundation has long believed in the interdisciplinary research approach”. Grein further commented that “the Foundation anticipates continued support of these efforts” and expressed hope that the base of benefactors will also continue to expand. On behalf of all the researchers at HCRI, we thank our supporters for the gift of research!

1. Committee on Facilitating Interdisciplinary Research, Committee on Science, Engineering, and Public Policy (2004). Facilitating interdisciplinary research. National Academies. Washington: National Academy Press, p. 2.
2. L. Michelle Bennett, Howard Gadlin, Christophe Marchand, National Cancer Institute Collaboration and Team Science Field Guide.  May 2018. https://www.cancer.gov/about-nci/organization/crs/research-initiatives/team-science-field-guide/collaboration-team-science-guide.pdf
3. NSF 18-058 Dear Colleague Letter: Growing Convergence Research. https://www.nsf.gov/pubs/2018/nsf18058/nsf18058
4. Siyuan Zhang, Jeremy Zartman, Brandon Ashfeld, and Danny Chen “Integrated Discovery of Novel Therapies for Cancer Brain Metastasis” 2014 grant.
5. Laurie Littlepage and Glen Niebur “A Novel Bone Bioreactor Used to Model Bone Metastasis Ex Vivo”; 2014 grant.
6. Pinar Zorlutuna and Siyuan Zhang “An Aging-mimicking Breast-on-Chip (ABoC) for Studying Effect of Aged Microenvironment on Breast Cancer Progression”; 2017 grant.
7. Sharon Stack, Matt Ravosa, and Pinar Zorlutuna, “Intra-peritoneal Mechanobiology and Tumor-Host Crosstalk in Ovarian Cancer”; 2017 grant.
8. Hsueh-Chia Chang and Sharon Stack “Nanomembrane-based Nucleic Acid Sensing for Simultaneous Detection of HPV and HPV-induced microRNAs in Oropharyngeal Cancers”; 2012 grant.  Hsueh-Chia Chang and Xin Lu “A Transformative and Commercializable Platform Technology for Exosome Assay:  Cancer Immunotherapy, Diagnostics and Biomarker Discovery”, 2020 grant.