AACR 2023

MIB News
AACR 2023

MIB Agents at the AACR Annual Meeting

MIB Agents attended the American Association of Cancer Research annual conference April 16-19th in Orlando. Over 21,000 scientists and oncology professionals from around the world gathered to learn and share about the latest in cancer research, with 600 oral presentations and 6,300 abstracts. The oldest and largest cancer research organization in the world, the AACR also has a very international membership, with more than 54,000 members from 131 countries and territories. A third of the AACR membership is international and a quarter of Annual Meeting participants in Orlando were from outside the U.S.

AACR CEO Margaret Foti, PhD, MD noted that the number of cancer survivors in the U.S. topped 18 million in 2022 thanks to a 32 percent reduction in the cancer death rate between 1991 and 2019.

Collaboration is a core mission of the AACR. In the past year, the AACR has organized meetings with more than 80 cancer center directors to develop impactful ways to collaborate in advancing cancer research and patient care.

The AACR’s groundbreaking Trust in Science Task Force will address the suboptimal participation of non-white racial and ethnic groups in clinical trials and develop strategies to improve bidirectional communications between cancer researchers and underserved patient populations.

Outgoing AACR President Lisa M. Coussens, PhD, FAACR, discussed addressing the roots of cancer health disparities by bolstering diversity in the cancer workforce by increasing representation from underserved communities. She announced the AACR High School Student Summer Internship Program, a new initiative that will provide students with dynamic and innovative STEM experiences through a four-week summer internship in collaboration with cancer centers with special emphasis to recruiting students from underrepresented and underserved communities.

Highlights from the Opening Plenary session

The theme of the opening plenary session was Advancing the Frontiers of Cancer Science and Medicine.

Deborah Schrag, MD, MPH, Chair of the Department of Medicine at Memorial Sloan Kettering Cancer Center, discussed the promise and challenges of scaling new cancer screening technologies, including the potential for multi-cancer early detection (MCED) tests to transform cancer screening.

David G. DeNardo, PhD, Professor of Medicine in the Oncology Division at Washington University School of Medicine, reviewed emerging therapeutic strategies to stimulate anti-cancer immunity, such as modulating the systemic impacts of cancer on the immune system and targeting the tumor microenvironment (TME).
Teresa A. Zimmers, PhD, Professor of Cell, Developmental, and Cancer Biology at Oregon Health & Science University’s Knight Cancer Institute, described important new insight into the complexity of cachexia and its impact on cancer outcomes.

Robert Yarchoan, MD, Chief of the HIV and AIDS Malignancy Branch at the National Cancer Institute, discussed the latest insights and advances in the prevention and treatment of malignancies in patients living with HIV.

Tomi Akinyemiju, PhD, Associate Professor of Population Health and Global Health at Duke University School of Medicine, discussed the ongoing pursuit of equity at the frontiers of cancer care and the need for both collective responsibility and individual action to effectively address and end cancer racial disparities.

NCI Director discusses Cancer Moonshot initiative and new National Cancer Plan

Monica M. Bertagnolli, MD, Director of the National Cancer Institute (NCI) discussed the NCI’s goals for the Cancer Moonshot initiative and the recently released National Cancer Plan.

On April 3, the U.S. Department of Health and Human Services released the National Cancer Plan, which was developed by the NCI. The plan provides a framework for everyone — across the federal government and all of society — to collaborate in ending cancer and realize the vision laid out in the Cancer Moonshot.

The plan includes eight essential goals and accompanying strategies that outline what must be accomplished to prevent more cancers, reduce deaths from the disease, and improve the lives of everyone after a diagnosis with cancer. These goals are: prevent cancer, detect cancers early, develop effective treatments, eliminate inequities, deliver optimal care, engage every person, maximize data utility, and optimize the workforce.

In conjunction with Bertagnolli’s address at the Annual Meeting, an NCI paper titled Opportunities for Achieving the Cancer Moonshot Goal of a 50% Reduction in Cancer Mortality by 2047 was simultaneously published in the AACR journal Cancer Discovery.

Pediatric Cancer Working Group

The AACR Pediatric Cancer Working Group town hall was led by outgoing chair Katherine Janeway, MD from Dana-Farber Cancer Institute and incoming chair Alejandro Sweet-Cordero from the  University of California, San Francisco. The panel topic was Cell-of-Origin and Tumor Heterogeneity in Childhood Cancers. Speakers included Sam Behjati, MA, BMBCh (Oxon), PhD, MRCPCH from Welcome Trust, Cambridgeshire, United Kingdom, Mariella G. Filbin, MD, PhD from Dana-Farber Cancer Institute, and Frank Westermann, MD from the German Cancer Research Center, Heidelberg, Germany.

NCI session with patient advocates

The NCI held a special session with Amy Williams, director of NCI’s Office of Advocacy Relations and Dr. Dan Gallahan, director of NCI’s Division of Cancer Biology for patient advocates to provide an overview of the NCI’s scientific portfolio and how OAR works with the entire cancer advocacy community to create a culture of advocate engagement at the NCI.

FDA Oncology Center of Excellence

The FDA Oncology Center of Excellence (OCE) held a special session for patient advocates to provide an overview of their research and educational outreach projects and programs to advance the development and regulation of medical products for patients with cancer.

Using Real World Evidence to Advance Pediatric Cancer Drug Development

This panel included leading experts from academia and the Food and Drug Administration (FDA) who provided their unique perspectives as to how emerging data and evidence may guide translational and clinical pediatric cancer research efforts. Amy Barone provided perspective from the FDA.  Gregory Reaman from the NIH discussed CCDI (Childhood Cancer Data Initiative), and the data catalog which includes 41 resources and 203 datasets. Project Everychild has collected genomic data on 889 patients and clinical data on 980 patients.Sam Volchenboum discussed the Pediatric Cancer Data Commons.

Meeting Highlights from Final Plenary Session
Clinical research and clinical trials

There were more than 250 clinical trial presentations at the meeting in four key areas this year — immunotherapy moving to early stages and novel combinations; success in targeting genetic abnormalities, particularly DNA damage response and RAS pathways; developing treatments for rare cancers; and bispecifics and novel agents for hematologic malignancies.

A pair of studies, TRESR and ATTACC, showed positive results combining poly (ADP-ribose) polymerase (PARP) inhibitors with ataxia-telangiectasia and Rad3-related (ATR) inhibition. The hypothesis is that ATR inhibition would block recovery from PARP inhibitor-induced DNA damage, leading to cell death. The trials evaluated the ATR inhibitor camonsertib in combination with one of three PARP inhibitors — talazoparib, niraparib, or olaparib — in patients with advanced solid tumors harboring DNA damage response alterations. The clinical benefit rates ranged from 41 percent to 59 percent across the three combinations.  It didn’t matter which PARP inhibitor was chosen as a partner. Benefit was seen across multiple tumors regardless of previous PARP inhibitor treatment or the presence of platinum-resistant tumors.

Arm N of the AcSé-ESMART trial used olaparib plus ceralasertib in children with advanced malignancies. There were no differences in the DDR pathway alterations in adults versus children.  Of 18 children, there were two confirmed partial responses, one unconfirmed partial response, and eight patients with stable disease.
This concept of matching genetic alterations to the treatment is being evaluated in adults and pediatric oncology in multiple trials.

Basic science and translational research

The complexity of tumors was a key theme.  Conventional thinking imagines the tumor microenvironment (TME) as a food desert with T cells and tumor cells competing for the same nutrients. In reality, the TME is more a swamp of metabolic byproducts and some of these potentially toxic wastes can modulate immune responses.

During the symposium Immunometabolism and Tumor Microenvironment, three researchers explored how metabolic components can impact immune responses and examined strategies that might alter the metabolic landscape to promote antitumor immunity.

Another symposium, Emerging Clinical Strategies for Myeloid Cell Modulation in Cancer, examined new approaches under development to therapeutically target myeloid cells, including strategies to deplete, inhibit, reprogram, or activate myeloid cells. A key take-home message from the session is that sex matters.  Sex hormones can modulate antitumor immunity differently in males and females, which can affect immunotherapy response.
Additional topics included the effects of stress, obesity, aging, and the microbiome on cancer; mechanisms of metastasis; comorbidities and cachexia; and tumor evolution; among others.

Prevention, early detection, population sciences, and disparities research

Population science was covered in three dedicated advances sessions that examined important topics like COVID-19 and cancer, new studies in implementation science and behavioral economics, and the etiology of omics and approaches to better use omics to inform personalized cancer prevention, treatment, and interception in high-risk individuals.

The session Behavioral Economics and Nudges to Improve Cancer Care examined the impact of low-cost, sustainable interventions (or “nudges”) to improve cancer care and outcomes. Another series of advanced sessions focused on the science of cancer disparities.

The session Disparities and Cancer Outcomes explored the concept of allostatic load, a measure of cumulative physiological stress and burden across major regulatory systems. Recent disparities research suggests that differences in cancer rates and cancer outcomes in different racial groups have roots in both societal structures and biology.

The session Novel Approaches to Personalized Cancer Health Equity highlighted that Community engagement is key, but since not every researcher has that specialized skill set, hiring community members to serve as consultants could help bridge this gap.

Additional topics covered during the meeting included cancer interception, risk prediction, the management of hereditary cancers, and the impact of cancer on responses to COVID vaccination.

Osteosarcoma Abstracts

There were over 60 poster presentations at FACTOR specific to or related to osteosarcoma - here is a sampling:

Tumor-tumor cooperation during osteosarcoma lung metastasis is driven by interactions between lung epithelia and niche-initiating anchor cells
Ryan Roberts/Nationwide Children's Hospital

Patient-specific mapping of oncogenic structural changes in pediatric osteosarcoma
Andrew Clugston/UCSF - University of California San Francisco

Delineating the role of vesicular glutamate transporter SLC17A7 in osteosarcoma
Niveditha Nerlakanti/H. Lee Moffitt Cancer Center

Ubiquitin Specific Peptidase 37 promotes Osteosarcoma oncogenesis by interacting with PCNA and impacting constitutive replication fork movement.
Mayank Singh/All India Institute of Medical Science

SKP2 knockout induces macrophage infiltration in p53/Rb1 null transgenic mouse models of osteosarcoma and drives gene expression correlated with improved survival in patients
Alexander Ferrena/Albert Einstein College of Medicine

The role of Mycobacterium as a novel treatment for osteosarcoma
Kirsten Stefan/Knight Cancer Institute, Oregon Health & Science University

The effect of circulating CXCL10 on osteosarcoma metastasis using orthotopic xenograft mouse models
Tsz Kwong Man/Baylor College of Medicine

Clonal emergence of resistance to methotrexate in osteosarcoma barcoded PDX cells
Zhongting Zhang/The University of Texas MD Anderson Cancer Center

B7-H3-CAR T-cell therapy in immune-competent osteosarcoma models: Regnase-1 KO overcomes limited CAR T-cell expansion
Adeleye Adeshakin/St. Jude Children's Research Hospital

Remodeling the microenvironment of osteosarcoma lung metastases with inhaled CSF-1Ri immunotherapy
Fatemah Sunbul/Virginia Commonwealth University - VCU

Loss of LRRC15 in osteosarcoma cells disrupts extracellular matrix integration, intercellular communication, and differentiation
Sanjit Mukherjee/National Institutes of Health

Exploration of multiple immunotherapy modalities in osteosarcoma
Payal Agarwal/Auburn Univ. College of Veterinary Medicine

PEPN2011: a phase 1/2 study of tegavivint in children, adolescents, and young adults with recurrent or refractory solid tumors, including lymphomas and desmoid tumors: a report from the pediatric early phase clinical trials network
Sarah Whittle/Texas Children's Cancer and Hematology Center

A multimodel preclinical platform to evaluate photodynamic therapy as a strategy to reduce local recurrence in myxofibrosarcoma and osteosarcoma
Chiara Spadazzi/IRCCS Istituto Romagnolo

MAPK-driven MCL1 expression promotes osteosarcoma survival in the metastatic niche
Camille McAloney/Nationwide Children's Hospital

Protein aggregation in sarcoma as a target for therapy
Sara Sartini/UCLA - University of California Los Angeles

Fluoxetine mediate radiosensitivity and inhibit metastasis of osteosarcoma cells via RANK/RANKL signaling
Peggy Tan/China Medical University

Epigenetic modulation of NK cells to improve tumor trafficking and enhance therapeutic efficacy against osteosarcoma
Ariana Anjier/University of Louisiana At Lafayette

Cross-presented serine proteases as immunotherapy targets for lung cancer and osteosarcoma
Amber Gibson/UT MD Anderson Cancer Center

ENLIGHTen-01: a phase 1 study of fluorescein-specific (FITC-E2)-car T cells in combination with folate-fluorescein (UB-TT170) for osteosarcoma
Catherine Albert/Seattle Children's Research Institute

The transcription factor ZEB1 shapes osteosarcoma aggressiveness by affecting tumor cell differentiation and stemness features
Caterina Cascini/Fondazione IRCCS Istituto Nazionale dei Tumori

WNT5B drives osteosarcoma stemness, metastasis and chemoresistance
Rachel Perkins/University of Tennessee Health Science Center

Stage-restricted osteoblasts specify signatures of osteosarcoma molecular subtypes
Jianning Tao/Sanford Research, South Dakota

TrkA+ sensory neurons modulate macrophage phenotype in osteosarcoma
Qizhi Qin/Johns Hopkins University School of Medicine

Bone mechanics influence cancer stem cell formation in osteosarcoma
Zunaira Shoaib/University of Illinois at Urbana-Champaign

Alteration of malignancy and histone-H3 lysine-methylation status in osteosarcoma cells which acquire methotrexate resistance in vitro
Yusuke Aoki/Graduate School of Medicine, University of the Ryukyus

Transcriptome analysis of Small Cell Osteosarcoma reveals an embryonic stem cell-like phenotype
Maria Antonella Laginestra/IRCCS Istituto Ortopedico Rizzoli

attIL12-T cell therapy destructs cancer-associated fibroblasts and extracellular matrix in heterogeneous osteosarcoma xenograft models
Jiemiao Hu/UT MD Anderson Cancer Center

Evaluation of tumor draining lymph nodes in dogs with spontaneously arising osteosarcoma using single-cell sequencing
Samuel Brill/Colorado State University, College of Veterinary Medicine & Biomedical Sciences

Inhibition of discoidin domain receptor 1 (DDR1) as a new therapeutic strategy for osteosarcoma
Zhenfeng Duan/University of Miami

Two epigenetically distinct cellular states in osteosarcoma are regulated by a state-specific set of transcription factors driving differential drug response
Eunice Lopez Fuentes/UCSF - University of California San Francisco

Clonal mapping phylogenetic and transcriptomic analysis of an M36 PDX amputation lung metastatic osteosarcoma model
Sylvester Jusu/The University of Texas MD Anderson Cancer Center

The Osteosarcoma and Leiomyosarcoma Count Me In Projects of the Cancer Moonshot funded PE-CGS Network directly engage patient participants in genomics research
Katherine Janeway/Dana-Farber Cancer Institute

Targeting RNA N<sup>6</sup>-methyladenosine methyltransferase, METTL3 activates p53 and apoptosis pathways in osteosarcoma cells
Seungjae Shin/Seoul National University College of Medicine

TBL1, a multifunctional transcriptional regulator, is highly expressed in osteosarcoma and correlates with activated beta catenin
Kimberly Holloway/Iterion Therapeutics

Omacetaxine reduces c-MYC expression and demonstrates antitumor effects in osteosarcoma
Kristen Farrell/Colorado State University

A potent and selective small molecule inhibitor of CSF-1R ABSK021 demonstrates strong efficacy in preclinical models of osteosarcoma
Nannan Xhang/Abbisko Therapeutics

Myc-regulated miR17, 20a modulate RANK expression in osteosarcoma
Bikesh Nirala/Texas Children's Cancer Center/Baylor College of Medicine

Targeting urea cycle dysfunction to prevent and treat osteosarcoma
Rachel Offenbacher/The Children's Hospital at Montefiore

Therapeutic targeting of BET bromodomain proteins increases DNA damage and potentiates salvage therapy in osteosarcoma xenografts derived from patients with replication stress signatures
Niknam Riyahi/Indiana University School of Medicine

Osteosarcoma patient-derived xenografts derived from naive and pretreated metastatic patients with high-risk CDK4/6 hyperactivation signatures are sensitive to dual inhibition of CDK4/6 and PI3K/mTOR
Farinaz Barghi/Indiana University School of Medicine

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