Spring 2025 | XL Edition
Several important concepts emerged from the Forum, including the need to understand the mechanisms that connect the formation of structural variants to their functional impact on the tumor; understanding extrachromosomal DNA biology; using synthetic biology approaches, such as building chromosomes, to elucidate cancer biology; and identifying whether recurrent chromosomal alterations can be targeted therapeutically. Topics covered in the Forum which focused on metastasis included: novel metabolic drivers of metastatic outgrowth (glutathione transferases; polyamine and propionate metabolism; palmitoylation of laminin in immune cells; and the purine salvage pathway); a putative function for sildenafil (Viagra®) in cancer; the activities of macrophages and neutrophils in pollution-dependent lung cancer; unique exploitable features of ferroptosis, particularly in epithelial- to-mesenchymal transition; and an emerging understanding of transfer RNA synthesis in metastatic cells 4 . At the conclusion of the meeting, open questions in the field were addressed, such as identifying plasma biomarkers of metastasis for early diagnosis; the potential of AI in drug design and diagnosis; and understanding the heterogeneity of metastatic cells in relation to metastatic growth. After the Forum had concluded, the Chairs learned that several collaborations had been established at the meeting, including with the new Forbeck Scholars. An oncogene is a gene with the potential to cause cancer 6 . Genes in tumor cells are often mutated, or expressed at unusually high levels. If normal genes that promote cellular growth are up-regulated (via a gain-of-function mutation), they will predispose the cell to become malignant; these genes are termed oncogenes. Most normal cells undergo apoptosis (a programmed form of rapid cell death) when critical functions malfunction. Oncogenes usually originate as proto-oncogenes, i.e. normal genes that are involved in cell growth and proliferation or inhibition of apoptosis. Activated oncogenes can enable cells to avoid apoptosis and instead the cells survive and proliferate. Usually multiple oncogenes, plus mutated apoptotic or tumor suppressor genes, will all act together to cause cancer. Since the 1970s, dozens of oncogenes have been identified in human cancer and many cancer drugs target the proteins encoded by these oncogenes. The Forum participants discussed the latest developments in fusion oncogene research. UPDATES ON KEY ISSUES IN CANCER RESEARCH Recent research on interactions between malignant cells and the micro-environment has shown that tumor- host interactions extend far beyond the local micro- environment 5 . Tumors not only respond to, but actively affect, the functioning of host organs at distant anatomic sites. The purpose of the Environment, Host and Tumor Interactions Forum was to examine the mechanisms by
which environmental factors affect whole-body physiology, and how this affects tumor biology and pathogen host interactions. The role of the immune system in cancer was a major discussion topic at the meeting, especially as it affects the efficacy of immunotherapy. It is important to understand why some cancers respond well to immunotherapy, while others do not. Mitochondria play a more complex role in cancer evolution than previously thought. Organelles, including mitochondria, release factors that control immune responses, hypoxic responses, cellular differentiation and survival. The impact of lifestyle interventions, e.g. diet and exercise, on inflammatory processes was a major focus of the meeting. It is known that specific dietary interventions can affect tumor growth and cachexia. The Forbeck Forum on Cellular Quiescence and Tumor Dormancy focused on laboratory research into cellular mechanisms involved in tumor latency, inactivity and aging 7 . Key determinants of reversible and irreversible cell cycle arrest are being identified; and the depth of quiescence is being measured in human cells. The mechanisms by which quiescent cells maintain their proliferative potential are being analyzed. A new pathway that suppresses DNA replication competence in early quiescence has been identified. It is now known that cells can transition from quiescence to senescence without proliferating. Experiments on gene- edited colon organoids have demonstrated that a cell’s phenotype is affected by the order in which somatic mutations are introduced. The Forum provided multiple opportunities for extensive discussions by researchers working in this important field.
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