Tumor microenvironment and immunology of ovarian cancer: 12th Biennial Rivkin Center Ovarian Cancer Research Symposium

The 12th Biennial Ovarian Cancer Research Symposium organized by the Rivkin Center for Ovarian Cancer and the American Association for Cancer Research held on September 13–15, 2018 covered cutting edge and relevant research topics in ovarian cancer biology and therapy. Sessions included detection and prevention, genomics and molecular mechanisms, tumor microenvironment and immunology, novel therapeutics, and an education session. In this article we provide an overview of the key findings presented in the tumor microenvironment and immunology session.

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Introduction: the 12th Biennial Rivkin Center Ovarian Cancer Research Symposium

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2019-000522 ◽

2019 ◽

Vol 29 (Suppl 2) ◽

pp. s1-s1

Author(s):

Nita J Maihle ◽

Douglas A Levine ◽

Kiran Dhillon ◽

Deborah Kay Armstrong

Keyword(s):

Ovarian Cancer ◽

Cancer Research ◽

Tumor Microenvironment ◽

Molecular Mechanisms ◽

American Association ◽

Cancer Genomics ◽

Novel Therapeutics ◽

Cancer Tumor

In September 2018, the 12th Biennial Ovarian Cancer Research Symposium was presented by the Rivkin Center for Ovarian Cancer and the American Association for Cancer Research, in Seattle, WA, USA. The 2018 Symposium focused on four broad areas of research: Detection and Prevention of Ovarian Cancer, Genomics and Molecular Mechanisms of Ovarian Cancer, Tumor Microenvironment and Immunology of Ovarian Cancer, and Novel Therapeutics: Response and Resistance of Ovarian Cancer. In addition, a special panel on the 'Role of Advocates in Ovarian Cancer Research’ was featured.

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Meeting report from the 2018 12th Biennial Ovarian Cancer Research Symposium detection and prevention of ovarian cancer

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2019-000454 ◽

2019 ◽

Vol 29 (Suppl 2) ◽

pp. s2-s6 ◽

Cited By ~ 1

Author(s):

Wa Xian ◽

Sophia George

Keyword(s):

Ovarian Cancer ◽

Cancer Research ◽

Early Detection ◽

Molecular Mechanisms ◽

Effective Means ◽

Meeting Report ◽

Clear Understanding ◽

High Grade ◽

Cellular Origin ◽

Oral Presentations

The objective of this review is to summarize recent research advances in the detection and prevention of ovarian cancer and discuss the experts’ opinions of future directions. The 12th Biennial Ovarian Cancer Research Symposium was held in Seattle, Washington, in September 2018. At this meeting, experts in ovarian cancer research gathered to present and discuss recent breakthroughs and their visions of future ovarian cancer research. Session 1 of the symposium focused on the detection and prevention of ovarian cancer. It included two invited oral presentations from Ranjit Manchanda, MD, PhD (Barts Cancer Institute) and Rosana Risques, PhD (University of Washington). Another eight oral presentations were selected from abstract submissions. Fifteen abstracts were presented in poster format. These presentations covered topics including cellular origin of high-grade serous cancer, risk factors for ovarian cancer, new methods for early detection of ovarian cancer, mechanisms underlying ovarian cancer development, and new therapeutic approaches for preventing ovarian cancer from forming or progressing. In conclusion, a clear understanding of the cellular origin and molecular mechanisms underlying the initiation of high-grade serous cancer is essential for developing effective means for early detection and prevention of this most devastating type of ovarian cancer. Recognizing the complexity of ovarian cancer and appreciating that ovarian cancer is not a single disease will help us to generate proper models, design rational experiments, and collect and analyze patient data in a meaningful way. A concerted effort in the field will help to bridge the basic science and clinical applications and lead to more precise and effective detection and treatment.

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Organoid Models for Cancer Research

Annual Review of Cancer Biology ◽

10.1146/annurev-cancerbio-030518-055702 ◽

2019 ◽

Vol 3 (1) ◽

pp. 223-234 ◽

Cited By ~ 9

Author(s):

Hans Clevers ◽

David A. Tuveson

Keyword(s):

Cancer Research ◽

Tumor Microenvironment ◽

Personalized Medicine ◽

High Throughput ◽

Stromal Cells ◽

Transcriptome Sequencing ◽

Cancer Biology ◽

Three Dimensional ◽

Model Systems ◽

Liver Cancers

Organoid cultures have emerged as powerful model systems accelerating discoveries in cellular and cancer biology. These three-dimensional cultures are amenable to diverse techniques, including high-throughput genome and transcriptome sequencing, as well as genetic and biochemical perturbation, making these models well suited to answer a variety of questions. Recently, organoids have been generated from diverse human cancers, including breast, colon, pancreas, prostate, bladder, and liver cancers, and studies involving these models are expanding our knowledge of the etiology and characteristics of these malignancies. Co-cultures of cancer organoids with non-neoplastic stromal cells enable investigation of the tumor microenvironment. In addition, recent studies have established that organoids have a place in personalized medicine approaches. Here, we describe the application of organoid technology to cancer discovery and treatment.

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Genomics and molecular mechanisms of high grade serous ovarian cancer: the 12th Biennial Rivkin Center Ovarian Cancer Research Symposium

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2019-000490 ◽

2019 ◽

Vol 29 (Suppl 2) ◽

pp. s7-s11

Author(s):

Erinn B Rankin

Keyword(s):

Ovarian Cancer ◽

Cancer Research ◽

Dna Repair ◽

Molecular Mechanisms ◽

New Technologies ◽

Serous Carcinoma ◽

High Grade ◽

Serous Ovarian Cancer ◽

Poster Presentations ◽

Oral Presentations

ObjectiveThe aim of this study was to review current research efforts in genomics and molecular mechanisms of high grade serous ovarian cancer, presented at the 12th Biennial Rivkin Center Ovarian Cancer Research Symposium, held at the University of Washington.MethodsThe 12th Biennial Rivkin Center Ovarian Cancer Research Symposium brought together leaders in the field to discuss recent advances in ovarian cancer research and therapy.ResultsThe genomics and molecular mechanisms of ovarian cancer session featured invited speaker presentations by Dr Alan D’ Andrea on ‘Deoxyribonucleic acid (DNA) repair in ovarian cancer’ and Dr Kathleen Cho on ‘Modeling the genomics of high grade serous carcinoma in the mouse’. Eight additional oral presentations and 46 poster presentations were selected from the submitted abstracts that highlighted current research efforts in p53, DNA repair, genomic instability and modeling disease in mice, and organoids in high grade serous ovarian cancer.ConclusionsNew technologies utilizing clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (CAS9) approaches in mice, organoids, and cell based screens continue to advance our knowledge of key molecular drivers of ovarian cancer initiation, progression, and drug resistance. Improved understanding of the mechanisms of poly ADP ribose polymerase inhibitor resistance may lead to new therapeutic strategies to enhance outcomes in women with high grade serous ovarian cancer.

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Estrogens and the Schrödinger’s Cat in the Ovarian Tumor Microenvironment

Cancers ◽

10.3390/cancers13195011 ◽

2021 ◽

Vol 13 (19) ◽

pp. 5011

Author(s):

Marija Gjorgoska ◽

Tea Lanišnik Rižner

Keyword(s):

Ovarian Cancer ◽

Tumor Microenvironment ◽

Tumor Growth ◽

Immune Cells ◽

Metabolic Pathways ◽

Ovarian Tumor ◽

Cancer Biology ◽

Thought Experiment ◽

Invasion And Metastasis ◽

Established Tumor

Ovarian cancer is a heterogeneous disease affecting the aging ovary, in concert with a complex network of cells and signals, together representing the ovarian tumor microenvironment. As in the “Schrödinger’s cat” thought experiment, the context-dependent constituents of the—by the time of diagnosis—well-established tumor microenvironment may display a tumor‑protective and ‑destructive role. Systemic and locally synthesized estrogens contribute to the formation of a pro-tumoral microenvironment that enables the sustained tumor growth, invasion and metastasis. Here we focus on the estrogen biosynthetic and metabolic pathways in ovarian cancer and elaborate their actions on phenotypically plastic, estrogen-responsive, aging immune cells of the tumor microenvironment, altogether highlighting the multicomponent-connectedness and complexity of cancer, and contributing to a broader understanding of the ovarian cancer biology.

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Epigenetic Crosstalk between the Tumor Microenvironment and Ovarian Cancer Cells: A Therapeutic Road Less Traveled

Cancers ◽

10.3390/cancers10090295 ◽

2018 ◽

Vol 10 (9) ◽

pp. 295 ◽

Cited By ~ 20

Author(s):

Yuliya Klymenko ◽

Kenneth P. Nephew

Keyword(s):

Ovarian Cancer ◽

Tumor Microenvironment ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Abdominal Cavity ◽

Malignant Ascites ◽

Bioactive Molecules ◽

Ovarian Cancer Cells ◽

Secondary Tumor

Metastatic dissemination of epithelial ovarian cancer (EOC) predominantly occurs through direct cell shedding from the primary tumor into the intra-abdominal cavity that is filled with malignant ascitic effusions. Facilitated by the fluid flow, cells distribute throughout the cavity, broadly seed and invade through peritoneal lining, and resume secondary tumor growth in abdominal and pelvic organs. At all steps of this unique metastatic process, cancer cells exist within a multidimensional tumor microenvironment consisting of intraperitoneally residing cancer-reprogramed fibroblasts, adipose, immune, mesenchymal stem, mesothelial, and vascular cells that exert miscellaneous bioactive molecules into malignant ascites and contribute to EOC progression and metastasis via distinct molecular mechanisms and epigenetic dysregulation. This review outlines basic epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA regulators, and summarizes current knowledge on reciprocal interactions between each participant of the EOC cellular milieu and tumor cells in the context of aberrant epigenetic crosstalk. Promising research directions and potential therapeutic strategies that may encompass epigenetic tailoring as a component of complex EOC treatment are discussed.

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Genome Chaos, Information Creation, and Cancer Emergence: Searching for New Frameworks on the 50th Anniversary of the “War on Cancer”

Genes ◽

10.3390/genes13010101 ◽

2021 ◽

Vol 13 (1) ◽

pp. 101

Author(s):

Julie Heng ◽

Henry H. Heng

Keyword(s):

Cancer Research ◽

Cancer Biology ◽

Molecular Mechanisms ◽

50Th Anniversary ◽

Genome Project ◽

Cancer Genes ◽

Cancer Evolution ◽

Volume Data ◽

Architecture Theory ◽

Genome Chaos

The year 2021 marks the 50th anniversary of the National Cancer Act, signed by President Nixon, which declared a national “war on cancer.” Powered by enormous financial support, this past half-century has witnessed remarkable progress in understanding the individual molecular mechanisms of cancer, primarily through the characterization of cancer genes and the phenotypes associated with their pathways. Despite millions of publications and the overwhelming volume data generated from the Cancer Genome Project, clinical benefits are still lacking. In fact, the massive, diverse data also unexpectedly challenge the current somatic gene mutation theory of cancer, as well as the initial rationales behind sequencing so many cancer samples. Therefore, what should we do next? Should we continue to sequence more samples and push for further molecular characterizations, or should we take a moment to pause and think about the biological meaning of the data we have, integrating new ideas in cancer biology? On this special anniversary, we implore that it is time for the latter. We review the Genome Architecture Theory, an alternative conceptual framework that departs from gene-based theories. Specifically, we discuss the relationship between genes, genomes, and information-based platforms for future cancer research. This discussion will reinforce some newly proposed concepts that are essential for advancing cancer research, including two-phased cancer evolution (which reconciles evolutionary contributions from karyotypes and genes), stress-induced genome chaos (which creates new system information essential for macroevolution), the evolutionary mechanism of cancer (which unifies diverse molecular mechanisms to create new karyotype coding during evolution), and cellular adaptation and cancer emergence (which explains why cancer exists in the first place). We hope that these ideas will usher in new genomic and evolutionary conceptual frameworks and strategies for the next 50 years of cancer research.

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