The purpose of this funding opportunity announcement (FOA) is to encourage investigator-initiated research efforts aimed at the development and characterization of state-of-the-art biomimetic tissue-engineered technologies for cancer research. Tissue-engineered in vitro and ex vivo systems that reflect the pathology and physiology of human disease are needed within the existing continuum of cancer models as new tools for studying cancer biology. Complementary implementation of these tools with existing cancer models is envisioned to ultimately lead to advances in cancer prevention, early detection of aggressive cancer, diagnosis and treatment. To date, only a handful of validated, biologically relevant tissue-engineered technologies exist for addressing specific cancer research questions. Recent technological advances in biomimetic tissue-engineered systems for the purposes of regenerative medicine could allow for new, innovative applications to cancer research. This FOA will support multidisciplinary research projects, and the funded investigators will collectively establish and participate in the Cancer Tissue Engineering Collaborative (TEC) Research Program. Funded investigators will also be invited to attend meetings associated with the NCI Physical Sciences-Oncology Network (PS-ON). The Cancer TEC research projects will focus on the development and characterization of in vitro systems using tissue-engineered technologies that mimic tumor biology to elucidate specific cancer phenomena that are otherwise difficult to examine in vivo.
This FOA is intended to encourage collaborative, multidisciplinary projects that engage the fields of cancer research with regenerative medicine, tissue engineering, biomaterials, and bioengineering. It is also expected to catalyze the advancement of innovative, well characterized in vitro and ex vivo systems available for cancer research, expand the breadth of these systems to several cancer types, and promote the exploration of cancer phenomena with biomimetic tissue-engineered systems beyond commonly studied areas such as cell migration and angiogenesis. Applicants are encouraged to leverage existing resources, such as in vivo models, imaging techniques, or computational models.
This FOA will support the development and characterization of state-of-the-art biomimetic tissue-engineered technologies for cancer research. Critical to this FOA will be characterizing the biological relevance of the tissue-engineered technologies. Applicants will be expected to take a novel engineering approach to define the critical features and parameters for the proposed system, how they are sufficient to mimic the physiology and pathology of the specific cancer question under study, and what characterization will be needed to validate the biological relevance of the system. Characterization could include the demonstration of relevant tissue structure, tumor biology, pathology, and physiological function that replicate the aspect of tumor biology that will be studied using the proposed system. The long-term goal is that the technologies might begin to have novel applications addressing questions in cancer biology, prevention, early detection of aggressive cancer, diagnosis and therapy.
Possible research areas of emphasis include the development and characterization of tissue-engineered biomimetic technologies, such as the following:
- Engineered native and/or synthetic scaffolds (e.g., hydrogels, nanofibers, 3D printing, decellularized matrix), bioreactors, and microfluidic devices to better understand the role of the structure and spatial organization in cancer initiation, progression, and treatment. The biomimetic systems could incorporate functionalized biomaterials that mimic tumor properties and are designed to probe cellular behaviors such as crowding, coupled interactions and/or cooperativity, and autocrine/paracrine behaviors at the molecular and cellular length scales.
- Cellular, mechanical, and secreted chemical factors of the tumor microenvironment such as stromal cells, exosomes, immune components, gradients of cytokines, growth factors and hormones, oxygen tension, pH, and extracellular matrix structure.
- Perfusion, lymphatics, interstitial pressure, passive flow, or immobile and soluble gradients to study the role of tumor physiology and immune responses on cancer biology, diagnosis, and treatment. Molecular probes could be incorporated to obtain quantitative and dynamic functional measurements.
- Technologies to facilitate measurements of bi-directional signaling, stresses, and dynamics of complex tumor systems, such as responsive materials, molecular probes, or genome editing tools that can be regulated or monitored with minimal invasiveness. Integration of advanced imaging modalities could allow visualization of dynamic cell and tissue processes across space and time.
- Engineered tissues capable of long-term culture to examine cancer initiation and dormancy over several weeks.
- Coupling with computational models to understand the emergence of tumor form, function, and heterogeneity from genetic or spatial information.
- Multi-organ engineered culture systems to probe organ-to-organ interactions during cancer progression and treatment.
- Systems to model cancer progression from pre-neoplastic lesions to invasive and metastatic disease; to develop biomimetic systems amenable to imaging for early detection of aggressive cancer, diagnosis and prognosis; and to select preventive and therapeutic agents.
The above list of possible research areas is intended to be a set of examples and is not a comprehensive list.