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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 433 records · Page 24
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Fracture Networks Imaging in CO2 Injection Zones in IBDP Site: An Unsupervised Machine Learning Application with Multiple Datasets

This is the conference paper accompanying a poster presentation at the 17th International Conference on Greenhouse Gas Control Technologies GHGT-17 held in Calgary, Canada, October 20-24 , 2024. This work highlights the integration of unsupervised machine learning (ML) techniques as a transformative tool for advancing understanding of CO2 injection into reservoirs that could potentially contribute to optimizing injection strategies and reservoir management, ultimately bolstering the efficacy and sustainability of CO2 storage.

Kumar, Abhash↗
DOE OSTI2024

Physics Coupled Machine Learning Applications for Geological Carbon Storage

This is the conference paper accompanying a poster presentation at the 17th International Conference on Greenhouse Gas Control Technologies GHGT-17 held in Calgary, Canada, October 20-24, 2024. In this paper, a physics-based method, CRM is coupled with the advanced artificial intelligence (AI)/machine learning (ML) models in virtual learning environment (VLE) for three-dimension details of reservoir responses and evaluations for a comprehensive understanding for CCS field operations and reservoir managements.

Liu, Guoxiang↗
DOE OSTI2024

Developing a Transferable Framework for CO2-Stimulated Geothermal Energy Enhancement: A Case Study

This is the conference paper accompanying a poster presentation at the 17th International Conference on Greenhouse Gas Control Technologies GHGT-17 held in Calgary, Canada, October 20-24, 2024. In this paper, we present innovative technologies to image key features, including CO₂-stimulated fracture imaging, CO₂ fluid sweep imaging and heat transfer and exchange imaging by leveraging multiple datasets and applying advanced AI/ML, multi-level data analytics, and data/information fusion to better understand the geothermal reservoir for enhanced recovery.

Liu, Guoxiang↗
DOE OSTI1989

Nuclear Safety [Vol. 30, No. 1, January-March 1989]

Nuclear Safety is a review journal that covers significant developments in the field of nuclear safety. Its scope includes the analysis and control of hazards associated with nuclear energy, operations involving fissionable materials, and the products of nuclear fission and their effects on the environment. Primary emphasis is on safety in reactor design, construction, and operation; however, the safety aspects of the entire fuel cycle, including fuel fabrication, spent-fuel processing, nuclear waste disposal, handling of radioisotopes, and environmental effects of these operations, are also treated. Table of Contents for this issue follows. GENERAL SAFETY CONSIDERATIONS: 1 International Conference on Thermal Reactor Safety: NUCSAFE 88 by A. P. Malinauskas and J. G. Pruett; ACCIDENT ANALYSIS: 18 Chernobyl Today: State of Research by A. Yu. Gagarinskii; CONTROL AND INSTRUMENTATION: 23 Problems Associated with Routine In-Plant Radioactive Effluent Monitoring Systems at U.S. Light-Water Reactors by Barry G. Wahlig, David M. Walker, Mahmoud R. Ghavi, and John M. Palms; DESIGN FEATURES: 34 Twentieth DOE/NRC Nuclear Air-Cleaning Conference by R. R. Bellamy, D. W. Moeller, and M. W. First, 46 Design Options for the Core Support Structure for Liquid-Metal-Cooled Reactor Plants by J. P. Burelbach, W. J. Kann, J. G. Saiveau, and R. W. Seidensticker; ENVIRONMENTAL EFFECTS: 53 The Radiological Consequences of the Chernobyl Accident by L. V. Konstantinov and A. J. González; WASTE AND SPENT FUEL MANAGEMENT: 70 Activities Related to Waste Management Compiled by E. G. Silver; OPERATING EXPERIENCES: 80 Fuel Performance Annual Report for 1986 by W. J. Bailey, 103 Safety Considerations Related to 12-Hour Shift Schedules by S. Gould, 105 Reactor Shutdown Experience Compiled by J. W. Cletcher, 108 Operating U.S. Power Reactors Compiled by E. G. Silver; RECENT DEVELOPMENTS: 130 General Administrative Activities Compiled by E. G. Silver, 140 Reports, Standards, and Safety Guides by D. S. Queener, 145 Status of Power-Reactor Licensing Activities Compiled by E. G. Silver, 153 Proposed Rule Changes as of Sept. 30, 1988; ANNOUNCEMENTS: 69 Northwestern University Short Course on Radiation Safety, 79 International Seminar on Fission Product Transport Processes in Reactor Accidents, 129 Harvard School of Public Health Offers Short Courses, 152 MIT Offers Summer Short Courses on Reactor Safety and Nodal Analysis, 152 Seminar on Use of PCs in Probabilistic Safety Analysis, 157 The Authors, 160 Indexes to Nuclear Safety, Volume 29.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗
DOE OSTI2025

Fracture Network Quantification during CO2 Injection

This is the conference paper accompanying an oral presentation at the ARMA 2025 (59th US Rock Mechanics/Geomechanics Symposium) Conference held in Santa Fe, New Mexico, June 8-11, 2025. Accurate mapping and quantification of these networks are essential to ensure the integrity of CO2 storage reservoirs, understand and reduce potential leakage, and maintain long-term environmental safety. This study presents a novel machine learning-driven approach, integrated with geomechanical analysis, to quantify fracture networks and assess their spatial distribution during CO2 injection. This paper combines microseismic monitoring data with principles of hydraulic diffusivity and geomechanical analysis to characterize reservoir scale fracture network. The novelty of our approach lies in its capacity to assimilate time-dependent pressure data and microseismicity into a cohesive framework, which not only identifies microseismic triggering fronts but also tracks fracture distribution during active injection. Besides, leveraging image log data and analysis our approach also provides another angle of the insights to solidate the fracture networks understanding and geomechanical impacts. Key results from our study include the detection of over 100 distinct fracture clusters across the injection site, with fracture orientations strongly correlated with the prevailing in-situ stress field.

CO2 storage and sequestration↗
DOE OSTI2025

University Data Management Pilot Utilizing the Nuclear Research Data System

Background In 2022, the Office of Science and Technology Policy (OSTP) issued a memo that significantly reshaped the landscape of access to federally funded research. The memo mandated that all taxpayer-funded research be made available to the public without delay upon publication, without an embargo period, superseding the 2013 OSTP public access policy. This public access policy promotes transparency and the democratization of knowledge, ensuring that the fruits of scientific endeavors funded by federal agencies could be immediately accessed and built upon by scientists, educators, students, and the public at large. To implement the requirements of the OSTP guidance and DOE Public Access Plan, the Office of Nuclear Energy (NE) has implemented public access plan guidance and has identified several areas where better data management practices would further expand public access to important nuclear energy related scientific data, reports, and other technical products. Significant NE supported efforts are already underway for data management and public access to important nuclear energy related data.1 2 To address gaps in data management practices, and improve retention and accessibility of data, NE is actively exploring enhanced data management options utilizing its high-performance computing resources administered by its Nuclear Scientific User Facility Program. A newly piloted system, the Nuclear Research Data System (NRDS) acts as a portal for data collection and dissemination. Nuclear Energy University Program Research and Development Portfolio According to Web of Science, NEUP has produced 2,345 journal publication that have been cited more than 61,000 times3 and countless conference proceedings. These publications are publicly available through OSTI.gov and in the open literature. Additional scientific and technical products including project milestones that are not publications and NEUP project final reports are vetted through OSTI.gov and released once reviewed and approved by DOE. Since 2009, NEUP has awarded close to 1,000 different R&D projects in technical areas across the NE research programs. As of June 2023, 512 NEUP reports are publicly available on OSTI. The underlying data for projects is still held at universities, and data transfer, co-location, and dissemination has not occurred in a systematic way. NEUP data is currently accessible through myriad university-based data repositories, or through direct requests to PIs. The program identified this patchwork of repositories, or often lack of publicly available data, as a significant barrier to an organized, accessible, and comprehensive solution to sharing data with the larger nuclear energy community. Approach The goal of this pilot project is to establish a pathway to a consolidated long-term repository for NEUP project data. To accomplish this goal, the pilot strives to accomplish the following objectives: Establish data collection standards, including a standard set of required supplementary information to contextualize and support raw data files. Work with the HPC group collect and upload information and to modify the NRDS system, as needed, to support a standardized approach. Resolve potential barriers to successful roll out of an expanded data collection strategy, including modifying data management plan guidelines and establishing a document and data release process that accounts for potential intellectual property and/or export control concerns. Results Overall, the pilot was successful in collecting 8,982 raw and processes data files, 220 reports, 56 calibration files, and 5,931 other supplementary documents. Supplementary documents included experimental plans, methods, journal publications and conference proceedings, milestone reports, and final reports. Figure 2 shows the number of data sets and supplementary project information provided by each project. Projects has significantly different input, depending on experimental data produced and completeness of the datasets provided.

Data collection↗
DOE OSTI2025

Effect of Loading Frequency on Fatigue Behavior of Additively Manufactured Short Fiber Thermoplastics via Infrared Thermography

Fracture, Fatigue, Failure, Damage Evolution and Thermomechanics & Infrared Imaging, Volume 4 of the Proceedings of the 2025 SEM Annual Conference & Exposition on Experimental and Applied Mechanics, the fourth volume of five from the Conference, brings together contributions to this important area of research and engineering. The collection presents early findings and case studies on a wide range of areas, including: • 3D Deformation and Failure • In-situ Techniques and Microscale Effects on Mechanical Behavior • Vibration and Cyclic Fatigue • Integration of Models and Experiments • Interface-Mediated Damage and Failure • Fracture and Fatigue in Brittle Materials • Material Characterizations Using Thermography • Fatigue, Damage & Fracture Evaluation Using Infrared Thermography

Pathak, Pharindra [Auburn University]↗
DOE OSTI2025

Status of the International Criticality Safety Benchmark Evaluation Project

The International Criticality Safety Benchmark Evaluation Project (ICSBEP) has continued its work generating evaluations of new and historical benchmark experiments since the last update to the nuclear criticality safety (NCS) community at the 12th International Conference on Nuclear Criticality Conference held in 2023. One additional version of the ICSBEP Handbook has been published since that update, and the Technical Review Group (TRG) held two in-person meetings to review and approve additional benchmarks. The 2022 and 2023 editions of the handbook were combined into one release (published in November 2024) and contained 13 new evaluations with 46 different configurations and two major revisions to existing evaluations. The 2024 version of the handbook, currently under publication review, will contain two new evaluations with 15 new configurations and one major revision to HEU-MET-FAST-028, the evaluation of Flattop with a uranium core. The ICSBEP TRG met again in person in April 2025 to review benchmarks for the 2025 ICSBEP Handbook and final comment resolution is currently ongoing. Many of the new benchmarks represent contemporaneous experiments that have been specifically optimized to provide validation cases relevant to the NCS community. One major area of focus for new critical experiments is to target the sparsely populated intermediate energy (or resonance) region. Another focus of many of the new benchmarks is to provide experiments sensitive to different materials, such as chlorine, hafnium, tantalum, titanium, molybdenum, chromium, and polymethyl methacrylate (PMMA, or Lucite). The ICSBEP continues to deliver high-quality, peer reviewed evaluations of integral experiments relevant to the nuclear data community.

HEU-MET-FAST-028↗
DOE OSTI1995

Nuclear Safety [Vol. 36, No. 2, July-December 1995]

Nuclear Safety is a journal that covers significant issues in the field of nuclear safety. Its primary scope is safety in the design, construction, operation, and decommissioning of nuclear power reactors worldwide and the research and analysis activities that promote this goal, but it also encompasses the safety aspects of the entire nuclear fuel cycle, including fuel fabrication, spent-fuel processing and handling, and nuclear waste disposal, the handling of fissionable materials and radioisotopes, and the environmental effects of all these activities. Table of Contents for this issue follows. THE CHORNOBYL ACCIDENT: 195 The Chornobyl Accident Revisited, Part III: Chernobyl Source Term Release Dynamics and Reconstruction of Events During the Active Phase, A. R. Sich; GENERAL SAFETY CONSIDERATIONS: 218 Second ANS Workshop on the Safety of Soviet-Designed Nuclear Power Plants, R. A. Bari; 234 Elements of a Nuclear Criticality Safety Program, C. M. Hopper; 243 Rickover, Excellence, and Criticality Safety Programs, R. E. Wilson; ACCIDENT ANALYSIS: 249 Transient Analysis of the PIUS Advanced Reactor Design with the TRAC-PF1/MOD2 Code, B. E. Boyack, J. L Steiner, S. C. Harmony, H. J. Stumpf, and J. F. Lime; 278 The Hierarchy-By-Interval Approach to Identifying Important Models that Need Improvement in Severe-Accident Simulation Codes, T. J. Heames, M. Khatib-Rahbar, J. E. Kelly, R. P. Jenks-Johnson, and Y.-S. Chen; 290 RELAP5/MOD3 Code Coupling Model, R. P. Martin; 299 Missiles Caused by Severe Pressurized-Water Reactor Accidents, R. Krieg; DESIGN FEATURES: 310 Validation of COMMIX with Westinghouse AP-600 PCCS Test Data, J. G. Sun, T. H. Chien, J. Ding, and W T. Sha; ENVIRONMENTAL EFFECTS: 321 Spent Nuclear Fuel Characterization for a Bounding Reference Assembly for the Receiving Basin for Off-Site Fuel, S. D. Kahook, R. L. Garrett, L. R. Canas, and M J. Beckum; OPERATING EXPERIENCES: 332 Reactor Shutdown Experience, Compiled by J. W. Cletcher; U.S. NUCLEAR REGULATORY COMMISSION INFORMATION AND ANALYSES: 335 Reactor Coolant System Blowdown at Wolf Creek on September 17, 1994, J. V. Kauffman and S. L. Israel; RECENT DEVELOPMENTS: 344 Reports, Standards, and Safety Guides, D. S. Oueener; 349 Proposed Rule Changes as of June 30, 1995; ANNOUNCEMENTS: 320 Symposium on Acceptability of Risk From Radiation—Application to Manned Space Flight; 320 24th DOE/NRC Nuclear Air Cleaning and Treatment Conference; 361 Radiation Biology and Radiation Protection— Modern Developments and Tendencies in Radiation Biology; 362 1997 IEEE Sixth Conference on Human Factors and Power Plants; 354 The Authors; 360 Reviewers of Nuclear Safety, Vol. 36.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗
DOE OSTI2020

Fundamental Physics of Ferroelectrics 2019

The workshop “Fundamental Physics of Ferroelectrics 2019” took place in January 2019 at USF and hosted around 80 participants (from both US and overseas) 32 of whom were early career professionals (PostDocs and graduate students). This was a 2.5 day workshop with 8 invited presentations, 39 oral presentations, and 27 posters. It brought together experts in the area of ferroelectrics and related materials and allowed for interactions, collaborations and exchange of ideas and progress. The invited speakers were Jorge Iniguez (University of Luxembourg), Manila Songvilay (University of Edinburgh), James Scott (St. Andrews), David Singh (University of Missouri), Philippe Ghosez (Université de Liège), Marin Alexe (University of Warwick), Takeshi Egami (University of Tennessee), Sergey Vakhrushev (Ioffe Physical Technical Institute), and Karin Rabe (Rutgers University). The DOE funding was used (i) to provide awards for junior participants (graduate students and PostDocs): best oral presentations (1st, 2nd and 3rd places) and best poster presentations (1st, 2nd and 3rd places). First places in both categories $\$ $300, second places in both categories $\$ $250 and third places in both categories $\$ $200. Information about the awardees available at the conference website.

36 MATERIALS SCIENCE↗
DOE OSTI2021

Interior Athabascan Energy Capacity Building Network (Final Report)

Tanana Chiefs Conference (TCC) is the traditional tribal consortium for the 37 federally recognized Tribes and villages of Interior Alaska. TCC is based on a belief in tribal self-determination and the need for regional Native unity. TCC is a nonprofit organization that works toward meeting the needs and challenges for more than 10,000 Alaska Natives (mostly Alaskan Athabaskans) in Interior Alaska. With support from DOE-OIE’s Inter-Tribal Technical Assistance grant, TCC’s goal was to expand and build on the solid foundation of work that the existing TCC Energy Program established through the creation of the Interior Athabascan Energy Network (IAEN). More specifically, the IAEN was designed to create a network of village-based energy champions across the interior and hold quarterly teleconferences and annual inperson meetings. Among the greatest impacts of the IAEN were the creation and support of realistic, communitybased energy projects that produced tangible results such as fuel savings and skills and capacity development among local staff as well as establishment of an energy team that included TCC staff, Tribal participants, technical consultants, and support agencies. The DOE-TA funding allowed us to provide technical assistance to our Tribal communities to develop energy projects, and to foster a network consisting of Tribal community members and energy experts that has strengthened the ability in the region to troubleshoot energy issues, develop meaningful projects, envision a clean energy future, and to share project successes and challenges. The funding from DOE was a catalyst for growth, has created opportunities for learning and knowledge sharing, and has led to the development of cost saving energy projects. Most importantly, the DOE project allowed energy champions around the region to share their knowledge, experiences, and expertise to create place-based solutions and has forged inter-Tribal relationships that will continue to be an asset for years to come. Through information exchange that occurred at out IAEN annual meetings and other events, this technical assistance grant award has spurred a spinoff project that is focused on establishing a collaborative of independent utilities that work together to solve energy problems and share services to operate and maintain their electric utilities. We have indentified at least 10 and possibly 12 communities that are interested in collaborating in managing their utilities to reduce costs and increase reliability. As well, by identifying and supporting Community Energy Champions in the Interior villages and adding capacity to the TCC Energy Program, we were able to create actionable community energy plans, develop specific projects, and increase local capacity, skills, and literacy around clean energy initiatives.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗
DOE OSTI2025

An Architectural Survey of the U12G Tunnel Historic District, Nevada National Security Site, Nye County, Nevada

The U.S. Department of Energy (DOE), in conjunction with the National Nuclear Security Administration Nevada Field Office (NNSA/NFO), proposes to demolish six buildings and three storage areas located at the U12g Tunnel portal area in Area 12 of the Nevada National Security Site (NNSS). The buildings are 12-358 (Signal Vault); 12-201800 (Storage Quonset Hut); 12-202555 (Walker Shack); 12-868 (Pipe Assembly); 12-B100933 (Electrical Shop); 12-B100944 (Conference Room); and Storage Area 1; Storage Area 2; and Storage Area 3. The buildings and storage areas were selected for demolition as part of the DOE’s Real Property Efficiency Plan to reduce the footprint of unused and non-operational facilities on the NNSS. They are all vacant and have no proposed uses for current or upcoming NNSS missions. Demolition activities constitute an undertaking subject to review under Section 106 of the National Historic Preservation Act (NHPA) (54 United States Code [USC] § 306101) and its implementing regulations, 36 Code of Federal Regulations (CFR) Part 800. Identification efforts began with resources proposed for demolition in federal Fiscal Year (FY) 23. Four buildings were proposed to be demolished in FY23 (12-358, 12-868, 12-201800, and 12-202555). These buildings and the U12g Tunnel Historic District (SHPO No. D444) were recorded in Identification, Evaluation, and Finding of Adverse Effect for the Proposed Demolition of Five Buildings in Area 12, Nevada National Security Site, Nye County, Nevada (Menocal et al. 2023). Identification efforts indicated three buildings (12-358, 12-201800, and 12-868) supported nuclear testing in the U12g Tunnel. The fourth building post-dated the use of U12g Tunnel for nuclear testing activities. The report recommended that three of the four buildings (12-358, 12-201800, 12-868) and the U12g Tunnel Historic District may be eligible for the National Register of Historic Places (NRHP). The report also found that the undertaking would have an adverse effect on the three buildings and on the historic district. The Nevada State Historic Preservation Office (SHPO) concurred with the report’s findings (Reed 2023). The U12g Tunnel was determined eligible as a historic district under the Secretary of the Interior’s (SOI) Significance Criterion A, at the local level, in the context of the Cold War as an underground testing environment for the development of nuclear weapons and to assess the effects of a nuclear explosion on materials and equipment with a period of significance from 1959 to 1971. It was also determined eligible under Significance Criterion C for embodying the distinctive characters of a horizontal tunnel complex used for nuclear testing and as a significant and distinguishable entity. The three buildings were determined to be contributing elements of the district. The undertaking was expanded with the addition of two buildings and three storage areas proposed to be demolished and located within U12g Tunnel Historic District in FY24. These five resources (12-B100933, 12-B100944, and Storage Areas 1, 2, and 3) were recorded in Supplemental Identification, Evaluation, and Finding of Effect for Additional Proposed Demolition at U12g Tunnel, Area 12, Nevada national Security Site, Nye County, Nevada (Brannan et al. 2024). Identification efforts indicated that the two buildings and Storage Area 1 supported nuclear testing in the U12g Tunnel. Storage Area 1 and Storage Area 2 post-dated the nuclear testing activities at U12g Tunnel and were not recommended as contributing elements to the district. The report also found that the undertaking would have an adverse effect on the newly identified buildings and one storage area and on the historic district. The SHPO concurred that the expanded undertaking would result in adverse effects to historic properties (Reed 2025). To resolve these adverse effects, NNSA/NFO, in consultation with the SHPO, is following standard mitigation as stipulated in the 2024 Programmatic Agreement DE-GM58-22NA25554 Among the U.S. Department of Energy and the Nevada State Historic Preservation Officer and the Advisory Council on Historic Preservation Concerning the Protection of Historic Properties on the Nevada National Security Site, Nye County, Nevada (hereafter referred to as the NNSS PA). The standard mitigation measures are outlined in Appendix D of the NNSS PA. As such, this architectural survey has been prepared in accordance with Appendix D of the NNSS PA and follows the report format outlined in Appendix F. It includes a historic context that describes the district’s origin, history, and support functions, its significance in the context of nuclear testing on the NNSS, and identifies contributing and non-contributing elements within the district. The report is accompanied by Architectural Resource Assessment (ARA) forms for individual resources and a Historic District Resource Assessment (HDRA) for the U12g Tunnel Historic District. In total, this architectural report identified 32 primary resources within the district boundary. Six of the primary resources were previously identified as contributing elements. An additional 17 resources are recommended as contributing elements to the district for a total of 23 contributing elements. The other nine resources identified are recommended as non-contributing elements to the district.

12-201800↗
DOE OSTI2023

Changing Microbiomes: A Symposium Hosted by the Microbiome Center at the Pennsylvania State University

The first “Changing Microbiomes” conference was successfully held at the Pennsylvania State University from May 31st – June 3rd, 2022. The overall goal of the symposium was to provide space for researchers to connect, exchange knowledge, and partner to advance our understanding of the mechanisms and applications of ecological and evolutionary changes in microbiomes across systems. The symposium spanned terrestrial and aquatic contexts and host-associated and free-living microbial communities. As such, the symposium will enable cross-disciplinary knowledge and idea exchange to promote future interdisciplinary collaborations. In addition, the program allowed formal and informal interactions between and among students, postdocs, PIs, and industry scientists.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2024

SIVB's 2024 In Vitro Biology Meeting Proceedings

SIVB's 2024 World Congress on In Vitro Biology took place in Saint Louis, Missouri, from June 8th to 12th, 2024. The conference featured renowned speakers from academic and non-academic institutions who will present recent advancements in critical areas like plant transformation, genome editing, synthetic biology, advanced breeding technologies, cellular agriculture, future food sources, chromosome engineering, epigenetics, artificial intelligence, and machine learning. The Society for In Vitro Biology (SIVB) has always considered the education and professional development of young researchers as an integral component of its mission. The 2024 World Congress program, along with SIVB’s student initiatives, was customized to foster scientific growth and professional development among students and young scientists empowering them in their professional journeys. The recording of the DOE supported "Single Cell RNA Sequencing" workshop was made publicly available at https://youtu.be/A0UnuYwefwg for easy retrieval and reference of all information shared during the live event, thereby increasing accessibility and knowledge transfer. Their are 14 articles in the proceedings and the full list of files is located at https://link.springer.com/journal/11626/volumes-and-issues/60-1/supplement.

10 SYNTHETIC FUELS↗
DOE OSTI2021

The PI3K/mTOR inhibitor Gedatolisib eliminates dormant breast cancer cells in organotypic culture, but fails to prevent metastasis in preclinical settings

Dormant, disseminated tumor cells (DTCs) are thought to be the source of breast cancer metastases several years or even decades after initial treatment. To date, a selective therapy that leads to their elimination has not been discovered. While dormant DTCs resist chemotherapy, evidence suggests that this resistance is driven not by their lack of proliferation, but by their engagement of the surrounding microenvironment, via integrin-β1-mediated interactions. Because integrin-β1-targeted agents have not been translated readily to the clinic, signaling nodes downstream of integrin-β1 could serve as attractive therapeutic targets in order to sensitize dormant DTCs to therapy. By probing a number of kinases downstream of integrin-β1, we determined that PI3K inhibition with either a tool compounds or a compound (PF-05212384; aka Gedatolisib) in clinical trials robustly sensitizes quiescent breast tumor cells seeded in organotypic bone marrow cultures to chemotherapy. These results motivated the preclinical study of whether Gedatolisib—with or without genotoxic therapy—would reduce DTC burden and prevent metastases. Despite promising results in organotypic culture, Gedatolisib failed to reduce DTC burden or delay, reduce or prevent metastasis in murine models of either triple-negative or estrogen receptor-positive breast cancer dissemination and metastasis. This result held true whether analyzing Gedatolisib on its own (vs. vehicle-treated animals) or in combination with dose-dense doxorubicin and cyclophosphamide (vs. animals treated only with dose-dense chemotherapies). These data suggest that PI3K is not the node downstream of integrin-β1 that confers chemotherapeutic resistance to DTCs. More broadly, they cast doubt on the strategy to target PI3K in order to eliminate DTCs and prevent breast cancer metastasis.

60 APPLIED LIFE SCIENCES↗