ヒトのがんにおける最も重要ながん抑制遺伝子であるp53に焦点を当て、基礎研究から臨床応用研究に至るまで、がん研究全体に対する広い視点からの研究内容を含むシンポジウムです。p53に関連する新しい基礎研究の進展を紹介するとともに、近年注目を集めているp53-MDM2経路を標的とした治療法や免疫療法など、p53をターゲットにした臨床研究の発展にも焦点をあて、活発な議論が交わされる場となることを期待しています。

Organoids can recapitulate the in vivo characteristics of cells and significantly contribute to elucidating the molecular mechanisms involved in the development and progression of cancer. Cancer progression is influenced by diverse factors in the microenvironment, such as inflammation, immune reaction, extracellular matrix remodeling, energy metabolism, and hypoxia. However, most of the molecular mechanisms promoting malignant progression remain unknown. Functional analysis using state-of-the-art technologies such as imaging, omics analysis, and novel devices in organoid culture systems has made it possible to analyze fundamental processes that take place in the microenvironment. Also, manipulating gene functions utilizing various genetic approaches in organoids has uncovered many novel gene functions that regulate differentiation, cell proliferation, and drug responses. In addition, constructing a library of patient-derived organoids and the stratification of cancers according to their responsiveness to cancer drugs or niche factors promote personalized medicine. Such analyses have provided new insights regarding cancer stem cells, cell plasticity, and the interactions between cancer cells and the immune system. These efforts will lead to identifying new therapeutic targets and establishing new therapies to cure malignant cancers for which no treatment is available. In this symposium, we will discuss the cutting edge of organoid research and the future direction.

Owing to the next-generation sequencing technology, gut microbiota research has recently advanced, revealing that gut bacteria are associated with various human diseases. This session will focus on recent cutting-edge topics, particularly the relationship between cancer and gut microbiota. We will discuss the relationship between colorectal cancer and E. coli positive for the mutagenic bacterial toxin, colibactin, as well as the analysis of the hereditary colorectal tumors and the gut microbiota. Additionally, this session will cover the involvement of bacterial species present within tumors in cancer progression, which has been recently elucidated. Furthermore, we will discuss the bacterial species that enhance the efficacy of immune checkpoint inhibitors (ICIs) and the potential of phage therapy targeting specific causative bacteria. We are also accepting one presentation from the public.

Animal models are essential tools for cancer research. To date, attempts have been made to develop animal models that faithfully recapitulate the molecular etiology and pathophysiology of human cancer, such as syngeneic/xenogeneic tumor-bearing mouse models, patient-derived xenografted mouse models, humanized mouse models and genetically modified mouse models. Furthermore, over the past two decades, the NIH/NIC in the USA has led the development of novel animal models using naturally occurring tumors in pet dogs, known as the “Comparative Oncology Project”, and has successfully accumulated critical knowledge through the biological studies including genome and informatics analysis. Moreover, the canine tumor models are now used to evaluate immunotherapy for rare cancers as the “Cancer Moonshot Project” in the United States, which is being promoted around the world. The aim of this symposium is to provide the basics from the cutting-edge mouse models to naturally occurring canine tumor models, as well as their practical application in future research. These approaches will greatly contribute to the innovative cancer research and therapeutic strategy.

In recent years, expectations for artificial intelligence (AI) technology have been increasing due to the rapid progress of machine learning, centered around deep learning. Since the development of Transformer in 2017, there has been significant progress in the field of generative AI, including large language models (LLMs), and AI is now being used in various fields of social life, as well as being a research tool. The medical field is no exception, and AI is being introduced into a wide range of medical research, from basic research to clinical research. According to the latest data from the US FDA, there are over 950 AI-equipped medical devices that have been approved by the FDA and are actually being used in clinical practice. Under these circumstances, this symposium will be held in collaboration with the Japanese Association for Medical Artificial Intelligence to present the results of cancer research using cutting-edge AI, from basic research to clinical applications, and to discuss future directions and issues.

Chimeric Antigen Receptor T-cell (CAR-T) therapy has achieved remarkable success in the treatment of hematological malignancies. However, significant challenges persist in the context of solid tumors, necessitating further innovation. In particular, the tumor microenvironment—characterized by an abundance of cancer stem cells and fibroblasts—as well as the antigenic heterogeneity and loss unique to solid tumors, underscore the limitations of current therapeutic approaches. Overcoming these obstacles requires the development of novel treatment strategies that go beyond conventional CAR-T therapies. This proposal aims to unlock the potential of "next-generation designer cell therapies powered by RNA science" by harnessing precise genomic information and state-of-the-art nucleic acid technologies. Recent advances in RNA modification measurement and profiling have not only paved the way for precision medicine in cancer treatment but have also expanded the potential of nucleic acid-based therapeutics. Specifically, we seek to address antigenic diversity through epitope broadening, regulate immune memory, and develop therapeutic strategies targeting cells beyond T cells, utilizing innovative models that accurately recapitulate human pathophysiology. Additionally, this initiative promotes groundbreaking technological advancements by young researchers, fostering transformative studies that aspire to pioneer the next generation of cancer therapies.

Alterations in lipid metabolism in cancer are understandable. The phospholipids that make up the cell membrane need to increase significantly due to the larger size of cancer cells. Increased cell proliferation also requires increased lipid synthesis.
These may be regarded as requirements for oncogenesis.
On the other hand, in recent years, accumulated studies revealed that changes in lipid metabolism actively drive oncogenesis. For example, the phospholipid hydrolysing enzyme sPLA2, which is essential in lymphomagenesis, is produced by tumour-associated macrophages (TAMs), suggesting that it is involved in oncogenesis through active alterations in lipid metabolism. In hepatocellular carcinoma, lipid accumulation by palmitic acid upregulates PD-L1 expression, suggesting that it induces aggressive tumour cell immune deviation.
In this symposium, we hope to stimulate active discussion and deepen our understanding of oncogenesis actively driven by such changes in lipid metabolism.

Research on lung cancer is progressing rapidly. Recent advances in whole-genome analysis technology are beginning to elucidate the entire picture of genomic abnormalities in lung cancer. Furthermore, with the advent of immune checkpoint inhibitors, molecular target drugs, antibody-drug conjugates, and bispecific antibodies, the perioperative treatment of lung cancer and the treatment of advanced stage cancers are undergoing dramatic changes. There is a feeling that bispecific antibodies will lead to a paradigm shift in the treatment of small cell lung cancer, where no major changes have been seen in treatment. In this symposium, we would like to share cutting-edge information on research into lung cancer. We are looking forward to many participants.

Brain tumors are notoriously refractory to treatment and are associated with dismal prognoses, underscoring the critical need for the development of novel therapies. In recent years, intensive research efforts have led to a rapid expansion of molecular understanding in brain tumors, leading to personalized medicine based on molecular abnormality and induction of molecularly targeted therapies. As well as primary brain tumors, the advancement of understanding of systemic cancers has enabled us to induce personalized therapies for metastatic brain tumors based on the molecular characteristics of the primary organ. However, these therapies contribute to the limited number of patients, with the remaining patients with dismal prognoses yet. This session will focus on recent advances in basic and translational research on malignant and metastatic brain tumors, highlighting the latest insights to understand brain tumor pathogenesis and advance novel therapeutic development. The program welcomes early-career investigators and graduate students and calls for abstracts from younger researchers and clinicians.

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