TY - JOUR AB - Resisting cell death is a pivotal hallmark of cancer and one of several increasingly actionable functional capabilities acquired by cancer cells to sustain their malignant state. Since the early 2000s, the discovery of multiple regulated cell death programmes has intensified interest in targeting these maladaptive traits that cancer cells employ to resist cellular demise. Among these, ferroptosis - the lethal outcome of iron-dependent (phospho)lipid peroxidation - stands apart from other regulated cell death mechanisms, as it is persistently suppressed while lacking an activating signal. In cancer research, ferroptosis has garnered considerable attention, with growing evidence suggesting that its deregulation intersects with other hallmarks of malignancy, thus positioning it as a pleiotropic target. However, in the absence of approved ferroptosis-based drugs and despite substantial advances in understanding the metabolic manoeuvres of cancer cells to evade ferroptosis, its heralded translational value remains somewhat speculative at this stage. This Review reconciles the biochemical foundation of ferroptosis, the evidence supporting its role in cancer biology and the potential strategies for rationalizing targeted therapies to induce ferroptosis-prone states in malignancies. Building on this foundation, we explore contentious issues surrounding ferroptosis, including its implications for immunogenicity and redox imbalances in cancer. Finally, we address critical considerations such as therapeutic windows and biomarkers of ferroptosis, which are prerequisites for successful translation into clinical oncology. AU - Wahida, A. AU - Conrad, M. C1 - 75752 C2 - 57975 CY - Heidelberger Platz 3, Berlin, 14197, Germany TI - Decoding ferroptosis for cancer therapy. JO - Nat. Rev. Cancer PB - Nature Portfolio PY - 2025 SN - 1474-175X ER - TY - JOUR AB - In this Tools of the Trade article, Hongcheng Mai describes the development of wildDISCO, an approach for whole-body immunolabelling, optical clearing and imaging in mice. AU - Mai, H. C1 - 68706 C2 - 54915 CY - Heidelberger Platz 3, Berlin, 14197, Germany TI - wildDISCO: HD whole-body imaging. JO - Nat. Rev. Cancer VL - 24 IS - 1 PB - Nature Portfolio PY - 2024 SN - 1474-175X ER - TY - JOUR AB - High-throughput methods to investigate tumour omic landscapes have quickly catapulted cancer specialists into the precision oncology era. The singular lesson of precision oncology might be that, for it to be precise, treatment must be personalized, as each cancer’s complex molecular and immune landscape differs from patient to patient. Transformative therapies include those that are targeted at the sequelae of molecular abnormalities or at immune mechanisms, and, increasingly, pathways previously thought to be undruggable have become druggable. Critical to applying precision medicine is the concept that the right combination of drugs must be chosen for each patient and used at the right stage of the disease. Multiple puzzles remain that complicate therapy choice, including evidence that deleterious mutations are common in normal tissues and non-malignant conditions. The host’s role is also likely to be key in determining treatment response, especially for immunotherapy. Indeed, maximizing the impact of immunotherapy will require omic analyses to match the right immune-targeted drugs to the individualized patient and tumour setting. In this Perspective, we discuss six key riddles that must be solved to optimize the application of precision oncology to otherwise lethal malignancies. AU - Wahida, A. AU - Buschhorn, L.* AU - Fröhling, S.* AU - Jost, P.J.* AU - Schneeweiss, A.* AU - Lichter, P.* AU - Kurzrock, R.* C1 - 66881 C2 - 53344 CY - Heidelberger Platz 3, Berlin, 14197, Germany SP - 43–54 TI - The coming decade in precision oncology: Six riddles. JO - Nat. Rev. Cancer VL - 23 IS - 1 PB - Nature Portfolio PY - 2023 SN - 1474-175X ER - TY - JOUR AB - Interleukins and associated cytokines serve as the means of communication for innate and adaptive immune cells as well as non-immune cells and tissues. Thus, interleukins have a critical role in cancer development, progression and control. Interleukins can nurture an environment enabling and favouring cancer growth while simultaneously being essential for a productive tumour-directed immune response. These properties of interleukins can be exploited to improve immunotherapies to promote effectiveness as well as to limit side effects. This Review aims to unravel some of these complex interactions. AU - Briukhovetska, D.* AU - Dörr, J.* AU - Endres, S. AU - Libby, P.* AU - Dinarello, C.A.* AU - Kobold, S. C1 - 62195 C2 - 50720 CY - Heidelberger Platz 3, Berlin, 14197, Germany SP - 481–499 TI - Interleukins in cancer: From biology to therapy. JO - Nat. Rev. Cancer VL - 21 PB - Nature Research PY - 2021 SN - 1474-175X ER - TY - JOUR AB - Ferroptosis is a recently recognized cell death modality that is morphologically, biochemically and genetically distinct from other forms of cell death and that has emerged to play an important role in cancer biology. Recent discoveries have highlighted the metabolic plasticity of cancer cells and have provided intriguing insights into how metabolic rewiring is a critical event for the persistence, dedifferentiation and expansion of cancer cells. In some cases, this metabolic reprogramming has been linked to an acquired sensitivity to ferroptosis, thus opening up new opportunities to treat therapy-insensitive tumours. However, it is not yet clear what metabolic determinants are critical for therapeutic resistance and evasion of immune surveillance. Therefore, a better understanding of the processes that regulate ferroptosis sensitivity should ultimately aid in the discovery of novel therapeutic strategies to improve cancer treatment. In this Perspectives article, we provide an overview of the known mechanisms that regulate sensitivity to ferroptosis in cancer cells and how the modulation of metabolic pathways controlling ferroptosis might reshape the tumour niche, leading to an immunosuppressive microenvironment that promotes tumour growth and progression. AU - Friedmann Angeli, J.P.* AU - Krysko, D.V.* AU - Conrad, M. C1 - 56088 C2 - 46808 CY - Macmillan Building, 4 Crinan St, London N1 9xw, England SP - 405-414 TI - Ferroptosis at the crossroads of cancer-acquired drug resistance and immune evasion. JO - Nat. Rev. Cancer VL - 19 IS - 7 PB - Nature Publishing Group PY - 2019 SN - 1474-175X ER - TY - JOUR AU - Gires, O. AU - Klein, C.A.* AU - Baeuerle, P.A.* C1 - 229 C2 - 27143 SP - 143 TI - On the abundance of EpCAM on cancer stem cells. JO - Nat. Rev. Cancer VL - 9 IS - 2 PB - Nature Publ. Group PY - 2009 SN - 1474-175X ER - TY - JOUR AB - Ionizing radiation is considered a non-threshold carcinogen. However, quantifying the risk of the more commonly encountered low and/or protracted radiation exposures remains problematic and subject to uncertainty. Therefore, a major challenge lies in providing a sound mechanistic understanding of low-dose radiation carcinogenesis. This Perspective article considers whether differences exist between the effects mediated by high- and low-dose radiation exposure and how this affects the assessment of low-dose cancer risk. AU - Mullenders, L.* AU - Atkinson, M.J. AU - Paretzke, H.G. AU - Sabatier, L.* AU - Bouffler, S.* C1 - 727 C2 - 26366 SP - 596-604 TI - Assessing cancer risks of low-dose radiation. JO - Nat. Rev. Cancer VL - 9 IS - 8 PB - Nature Publ. Group PY - 2009 SN - 1474-175X ER -