TRF1 and TRF2: pioneering targets in telomere-based cancer therapy.

This article presents an in-depth exploration of the roles of Telomere Repeat-binding Factors 1 and 2 (TRF1 and TRF2), and the shelterin complex, in the context of cancer biology. It emphasizes their emerging significance as potential biomarkers and targets for therapeutic intervention. Central to the shelterin complex, TRF1 and TRF2 are crucial in maintaining telomere integrity and genomic stability, their dysregulation often being a hallmark of cancerous cells. The article delves into the diagnostic and prognostic capabilities of TRF1 and TRF2 across various cancer types, highlighting their sensitivity and specificity. Furthermore, it reviews current strides in drug discovery targeting the shelterin complex, detailing specific compounds and their modes of action. The review candidly addresses the challenges in developing therapies aimed at the shelterin complex, including drug resistance, off-target effects, and issues in drug delivery. By synthesizing recent research findings, the article sheds light on the intricate relationship between telomere biology and cancer development. It underscores the urgency for continued research to navigate the existing challenges and fully leverage the therapeutic potential of TRF1, TRF2, and the shelterin complex in the realm of cancer treatment.

Riding the storm: managing cytokine-related toxicities in CAR-T cell therapy.

The advent of chimeric antigen receptor T cells (CAR-T) has been a paradigm shift in cancer immunotherapeutics, with remarkable outcomes reported for a growing catalog of malignancies. While CAR-T are highly effective in multiple diseases, salvaging patients who were considered incurable, they have unique toxicities which can be life-threatening. Understanding the biology and risk factors for these toxicities has led to targeted treatment approaches which can mitigate them successfully. The three toxicities of particular interest are cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and immune effector cell-associated hemophagocytic lymphohistiocytosis (HLH)-like syndrome (IEC-HS). Each of these is characterized by cytokine storm and hyperinflammation; however, they differ mechanistically with regard to the cytokines and immune cells that drive the pathophysiology. We summarize the current state of the field of CAR-T-associated toxicities, focusing on underlying biology and how this informs toxicity management and prevention. We also highlight several emerging agents showing promise in preclinical models and the clinic. Many of these established and emerging agents do not appear to impact the anti-tumor function of CAR-T, opening the door to additional and wider CAR-T applications.

Exploring treatment options in cancer: Tumor treatment strategies.

Traditional therapeutic approaches such as chemotherapy and radiation therapy have burdened cancer patients with onerous physical and psychological challenges. Encouragingly, the landscape of tumor treatment has undergone a comprehensive and remarkable transformation. Emerging as fervently pursued modalities are small molecule targeted agents, antibody-drug conjugates (ADCs), cell-based therapies, and gene therapy. These cutting-edge treatment modalities not only afford personalized and precise tumor targeting, but also provide patients with enhanced therapeutic comfort and the potential to impede disease progression. Nonetheless, it is acknowledged that these therapeutic strategies still harbour untapped potential for further advancement. Gaining a comprehensive understanding of the merits and limitations of these treatment modalities holds the promise of offering novel perspectives for clinical practice and foundational research endeavours. In this review, we discussed the different treatment modalities, including small molecule targeted drugs, peptide drugs, antibody drugs, cell therapy, and gene therapy. It will provide a detailed explanation of each method, addressing their status of development, clinical challenges, and potential solutions. The aim is to assist clinicians and researchers in gaining a deeper understanding of these diverse treatment options, enabling them to carry out effective treatment and advance their research more efficiently.

PARP11 inhibition inactivates tumor-infiltrating regulatory T cells and improves the efficacy of immunotherapies.

Tumor-infiltrating regulatory T cells (TI-Tregs) elicit immunosuppressive effects in the tumor microenvironment (TME) leading to accelerated tumor growth and resistance to immunotherapies against solid tumors. Here, we demonstrate that poly-(ADP-ribose)-polymerase-11 (PARP11) is an essential regulator of immunosuppressive activities of TI-Tregs. Expression of PARP11 correlates with TI-Treg cell numbers and poor responses to immune checkpoint blockade (ICB) in human patients with cancer. Tumor-derived factors including adenosine and prostaglandin E2 induce PARP11 in TI-Tregs. Knockout of PARP11 in the cells of the TME or treatment of tumor-bearing mice with selective PARP11 inhibitor ITK7 inactivates TI-Tregs and reinvigorates anti-tumor immune responses. Accordingly, ITK7 decelerates tumor growth and significantly increases the efficacy of anti-tumor immunotherapies including ICB and adoptive transfer of chimeric antigen receptor (CAR) T cells. These results characterize PARP11 as a key driver of TI-Treg activities and a major regulator of immunosuppressive TME and argue for targeting PARP11 to augment anti-cancer immunotherapies.

"Rigid-Flexible" Dual-Ferrocene Chimeric Nanonetwork for Simultaneous Tumor-Targeted Tracing and Photothermal/Photodynamic Therapy.

There is an urgent need to develop phototherapeutic agents with imaging capabilities to assess the treatment process and efficacy in real-time during cancer phototherapy for precision cancer therapy. The safe near-infrared (NIR) fluorescent dyes have garnered significant attention and are desirable for theranostics agents. However, until now, achieving excellent photostability and fluorescence (FL) imaging capability in aggregation-caused quenching (ACQ) dyes remains a big challenge. Here, for the only FDA-approved NIR dye, indocyanine green (ICG), we developed a dual-ferrocene (Fc) chimeric nanonetwork ICG@HFFC based on the rigid-flexible strategy through one-step self-assembly, which uses rigid Fc-modified hyaluronic acid (HA) copolymer (HA-Fc) and flexible octadecylamine (ODA) bonded Fc (Fc-C18) as the delivery system. HA-Fc reserved the ability of HA to target the CD44 receptor of the tumor cell surface, and the dual-Fc region provided a rigid space for securely binding ICG through metal-ligand interaction and π-π conjugation, ensuring excellent photostability. Additionally, the alkyl chain provided flexible confinement for the remaining ICG through hydrophobic forces, preserving its FL. Thereby, a balance is achieved between outstanding photostability and FL imaging capability. In vitro studies showed improved photobleaching resistance, enhanced FL stability, and increased singlet oxygen (1O2) production efficiency in ICG@HFFC. Further in vivo results display that ICG@HFFC had good tumor tracing ability and significant tumor inhibition which also exhibited good biocompatibility.. Therefore, ICG@HFFC provides an encouraging strategy to realize simultaneous enhanced tumor tracing and photothermal/photodynamic therapy (PTT/PDT) and offers a novel approach to address the limitations of ACQ dyes.

Construction of Hierarchically Biomimetic Iron Oxide Nanosystems for Macrophage Repolarization-Promoted Immune Checkpoint Blockade of Cancer Immunotherapy.

Cancer immunotherapy is developing as the mainstream strategy for treatment of cancer. However, the interaction between the programmed cell death protein-1 (PD-1) and the programmed death ligand 1 (PD-L1) restricts T cell proliferation, resulting in the immune escape of tumor cells. Recently, immune checkpoint inhibitor therapy has achieved clinical success in tumor treatment through blocking the PD-1/PD-L1 checkpoint pathway. However, the presence of M2 tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) will inhibit antitumor immune responses and facilitate tumor growth, which can weaken the effectiveness of immune checkpoint inhibitor therapy. The repolarization of M2 TAMs into M1 TAMs can induce the immune response to secrete proinflammatory factors and active T cells to attack tumor cells. Herein, hollow iron oxide (Fe3O4) nanoparticles (NPs) were prepared for reprogramming M2 TAMs into M1 TAMs. BMS-202, a small-molecule PD-1/PD-L1 inhibitor that has a lower price, higher stability, lower immunogenicity, and higher tumor penetration ability compared with antibodies, was loaded together with pH-sensitive NaHCO3 inside hollow Fe3O4 NPs, followed by wrapping with macrophage membranes. The formed biomimetic FBN@M could produce gaseous carbon dioxide (CO2) from NaHCO3 in response to the acidic TME, breaking up the macrophage membranes to release BMS-202. A series of in vitro and in vivo assessments revealed that FBN@M could reprogram M2 TAMs into M1 TAMs and block the PD-1/PD-L1 pathway, which eventually induced T cell activation and the secretion of TNF-α and IFN-γ to kill the tumor cells. FBN@M has shown a significant immunotherapeutic efficacy for tumor treatment.

mRNA vaccine development and applications: A special focus on tumors (Review).

Cancer is characterized by unlimited proliferation and metastasis, and traditional therapeutic strategies usually result in the acquisition of drug resistance, thus highlighting the need for more personalized treatment. mRNA vaccines transfer the gene sequences of exogenous target antigens into human cells through transcription and translation to stimulate the body to produce specific immune responses against the encoded proteins, so as to enable the body to obtain immune protection against said antigens; this approach may be adopted for personalized cancer therapy. Since the recent coronavirus pandemic, the development of mRNA vaccines has seen substantial progress and widespread adoption. In the present review, the development of mRNA vaccines, their mechanisms of action, factors influencing their function and the current clinical applications of the vaccine are discussed. A focus is placed on the application of mRNA vaccines in cancer, with the aim of highlighting unique advances and the remaining challenges of this novel and promising therapeutic approach.

A sequential multiple assignment randomized trial of symptom management for cancer survivors during treatment and their informal caregivers.

CONTEXT: Many cancer survivors and their informal caregivers experience multiple symptoms during the survivor's treatment. OBJECTIVE: Test relative effectiveness and optimal sequencing of two evidence-based interventions for symptom management. METHODS: In this sequential multiple assignment randomized trial (SMART), survivors of solid tumors with elevated depression or anxiety and their caregivers as dyads were initially randomized after baseline assessment in a 3:1 ratio to the Symptom Management and Survivorship Handbook (SMSH, N = 277 dyads) intervention or SMSH plus 8 weeks of telephone interpersonal counseling (TIPC, N = 97 dyads). After 4 weeks, survivors who were not responding (no improvement or worsening score on depression and/or anxiety item) to SMSH only and their caregivers were re-randomized to continue with SMSH alone (N = 44 dyads) to give it more time or to SMSH + TIPC (N = 44 dyads). Mixed effects and generalized linear models compared severity of depression, anxiety, and a summed index of 16 other symptoms over weeks 1-13 and week 17 between randomized groups and among three dynamic treatment regimes (DTRs). Dyads received SMSH only for 12 weeks (DTR1); SMSH for 12 weeks with 8 weeks of TIPC added from week 1 (DTR2); and SMSH for 4 weeks followed by the combined SMSH + TIPC for 8 weeks if no response at 4 weeks (DTR3). RESULTS: Survivors randomized initially to SMSH alone had significantly lower anxiety over weeks 1-13 compared to those randomized to the combined SMSH + TIPC. In comparing DTRs, survivor's anxiety was significantly lower at week 13 for DTR1 compared to DTR2 with no other main effects for survivors or caregivers. Exploratory moderation analyses indicated a potential benefit of adding TIPC for caregivers of non-responders with elevated baseline symptoms. CONCLUSION: SMSH + TIPC did not result in better symptom outcomes at week 17 than SMSH alone. Lower intensity SMSH may improve depression and anxiety symptoms for most survivors and their caregivers. TRIAL REGISTRATION: Clinicaltrails.gov ID number, NCT03743415; approved and posted on 11/16/2018.

Antibody targeting of anaerobic bacteria warms cold tumors and improves the abscopal effect of radiotherapy.

BACKGROUND: The combination of immune checkpoint inhibitors with radiotherapy can enhance the immunomodulation by RT and reduce the growth of distant unirradiated tumors (abscopal effect); however, the results are still not very satisfactory. Therefore, new treatment options are needed to enhance this effect. Our previous study showed that the combination of Bifidobacterium (Bi) and its specific monoclonal antibody (mAb) could target and alleviate hypoxia at the tumor site and act as a radiosensitizer. In this study, we explored the anti-tumor efficacy of quadruple therapy (Bi + mAb and RT + αPD-1). The current study also aimed to probe into the complex immune mechanisms underlying this phenomenon. METHODS: Constructed 4T1 breast and CT26 colon cancer tumor models. A comprehensive picture of the impact of constructed quadruple therapy was provided by tumor volume measurements, survival analysis, PET/CT imaging, immune cell infiltration analysis and cytokine expression levels. RESULTS: The abscopal effect was further amplified in the "cold" tumor model and prolonged survival in tumor-bearing mice. Bi can colonized in primary and secondary tumors and direct the mAb to reach the tumor site, activate complement, enhance the ADCC effect and initiate the innate immune response. Then combined with αPD-1 and radiotherapy to stimulate adaptive immune response and synergize with cytokines to expand the immune efficacy and generate effective anti-tumor immune response. CONCLUSIONS: Bi was used as an artificially implanted anaerobic target to cause a transient "infection" at the tumor, causing the tumor to become locally inflamed and "hot", and at the same time, mAb was used to target Bi to enhance the local immune effect of the tumor, and then combined with radiotherapy and αPD-1 to amplify the abscopal effect in multiple dimensions. Therefore, the present study provided a new idea for the multipotent immune-activating function of antibody-targeted anaerobic bacteria for the RT treatment of extensively metastasized cancer patients.

Barriers and facilitators of improved nutritional support for patients newly diagnosed with cancer: a pre-implementation study.

BACKGROUND: Disease-related malnutrition affects a significant number of patients with cancer and poses a major social problem worldwide. Despite both global and national guidelines to prevent and treat malnutrition, the prevalence is high, ranging from 20 to 70% in all patients with cancer. This study aimed to explore the current practice of nutritional support for patients with cancer at a large university hospital in Norway and to explore potential barriers and facilitators of the intervention in the Green Approach to Improved Nutritional support for patients with cancer (GAIN), prior to implementation in a clinical setting. METHODS: The study used individual interviews and a focus group discussion to collect data. Study participants included different healthcare professionals and patients with cancer treated at a nutrition outpatient clinic. The Consolidated Framework for Implementation Research (CFIR) was used to guide the thematic data analysis. RESULTS: Barriers connected to the current nutritional support were limited resources and undefined roles concerning responsibility for providing nutritional support among healthcare professionals. Facilitators included a desire for change regarding the current nutritional practice. The GAIN intervention was perceived as feasible for patients and healthcare professionals. Potential barriers included limited knowledge of technology, lack of motivation among patients, and a potential added burden experienced by the participating patients. CONCLUSIONS: The identification of the potential barriers and facilitators of the current nutritional support to patients with cancer will be used to plan the implementation of improved nutritional support in a randomized controlled trial for patients with cancer prior to clinical implementation. The current findings may be of value to others trying to implement either or both nutritional support and digital application tools in a clinical healthcare setting. TRIAL REGISTRATION: The study was registered in the National Institutes of Health Clinical trials 08/09/22. The identification code is NCT05544318.

MicroRNA-mediated metabolic regulation of immune cells in cancer: an updated review.

The study of immunometabolism, which examines how immune cells regulate their metabolism to maintain optimal performance, has become an important area of focus in cancer immunology. Recent advancements in this field have highlighted the intricate connection between metabolism and immune cell function, emphasizing the need for further research. MicroRNAs (miRNAs) have gained attention for their ability to post-transcriptionally regulate gene expression and impact various biological processes, including immune function and cancer progression. While the role of miRNAs in immunometabolism is still being explored, recent studies have demonstrated their significant influence on the metabolic activity of immune cells, such as macrophages, T cells, B cells, and dendritic cells, particularly in cancer contexts. Disrupted immune cell metabolism is a hallmark of cancer progression, and miRNAs have been linked to this process. Understanding the precise impact of miRNAs on immune cell metabolism in cancer is essential for the development of immunotherapeutic approaches. Targeting miRNAs may hold potential for creating groundbreaking cancer immunotherapies to reshape the tumor environment and improve treatment outcomes. In summary, the recognition of miRNAs as key regulators of immune cell metabolism across various cancers offers promising potential for refining cancer immunotherapies. Further investigation into how miRNAs affect immune cell metabolism could identify novel therapeutic targets and lead to the development of innovative cancer immunotherapies.

Rules of acupoint selection in treatment of cancer-related insomnia with acupuncture and moxibustion based on data mining technology. / åŸºäºŽæ•°æ®æŒ–æŽ˜æŠ€æœ¯æŽ¢æžé’ˆç¸æ²»ç–—è‚¿ç˜¤ç›¸å ³æ€§å¤±çœ çš„é€‰ç©´è§„å¾‹.

OBJECTIVES: To analyze the rules of acupoint selection in treatment of cancer-related insomnia with acupuncture and moxibustion by data mining technology. METHODS: The articles of cancer-related insomnia treated with acupuncture and moxibustion were searched from CNKI, Wanfang, VIP, SinoMed, PubMed, WOS, Cochrane, and Embase databases, from the inception of each database to January 5, 2024. The prescription database of acupuncture and moxibustion for cancer-related insomnia was established. The descriptive analysis was conducted on the use frequency, meridian tropism and distribution of acupoints. Using SPSS Modeler 18.0 Apriori algorithm, the association rules of acupoint prescriptions were analyzed. With Cytoscape3.9.1 software used, the complex network diagram was plotted, and the cluster analysis of high-frequency acupoints was performed by SPSS26.0 software. RESULTS: Forty-one articles were included, and 67 prescriptions were extracted with 89 acupoints involved, and the total use frequency was 447 times. The top 4 acupoints of the high use frequency were Baihui (GV20), Sanyinjiao (SP6), Shenmen (HT7) and Shenting (GV24). The included meridians were the governor vessel, the spleen meridian, the bladder meridian, the conception vessel, the heart meridian and the stomach meridian. The selected acupoints were mostly distributed on the head, the neck and and the upper and lower limbs. The special acupoints of the high use frequency included the five-Shu points, the crossing points and yuan-primordial points. Regarding acupoint combination, GV24, SP6, HT7, and GV20 were highly correlated. The three effective clusters were categorized among the top 12 acupoints of the high use frequency. CONCLUSIONS: In treatment of cancer-related insomnia with acupuncture and moxibustion, the principle focuses on supporting the healthy qi, eliminating pathogens, regulating yin and yang, promoting the circulation of the governor vessel for regulating the spirit, and tranquilizing the mind. The core acupoint prescription may includes GV24, SP6, HT7 and GV20；combined with Zusanli (ST36) and Yintang (GV4+) to enhance the therapeutic effect.

Effect of ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation on gastrointestinal reactions of malignant tumor patients undergoing chemotherapy. / éš”å§œç¸è”åˆæ¿é’ˆå¯¹æ¶æ€§è‚¿ç˜¤åŒ–ç–—æ‚£è€ èƒƒè‚ é“ååº”çš„å½±å“.

OBJECTIVES: To observe the efficacy and safety of ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in patients with malignant tumors. METHODS: Patients with malignant tumors and suffering from chemotherapy were randomly divided into control group (35 cases, 4 cases dropped off) and observation group (35 cases, 2 cases dropped off). The patients of the control group were treated by orally taking ondansetron hydrochloride tablets 8 mg/time, 3 times a day for 3 d, and those of the observation group treated by ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation of Zusanli(ST36), Neiguan(PC6), Tianshu(ST25), Zhongwan(CV12) and Guanyuan(CV4) once a day for a total of 3 d, based on the treatment of the control group. The patients' gastrointestinal reaction degree after the 1st , 2nd and the 3rd day of treatment were recorded. The Karnofsky performance status (KPS) score (0-100 points) was used for assessing the patients' quality of life. The TCM syndrome score (4 grades：no, mild, medium and severe, i.e. 0, 2, 4 and 6 points) was given according to the patients' severity of symptoms of spleen (stomach) qi deficiency (nausea and vomiting, abdominal distension after eating, belching, loss of appetite, weakness and laziness to speak, fatigue, and loose stool). The safety of the treatment was assessed by examining the patients' blood routine, liver function and kidney function, and the adverse reactions including blisters, allergies, burns and fainting during acupuncture treatment. RESULTS: After the 2nd and 3rd day of treatment, the patients conditions of vomiting and nausea in the observation group were significantly better than those of the control group (P<0.05). The TCM syndrome score and KPS score were significantly decreased in comparison with those of pre-treatment in both groups (P<0.05), and the TCM syndrome score was obviously lower in the observation group than in the control group (P<0.05). No significant differences were found between the two groups in the KPS score after the treatment , and in the levels of white blood cells (WBC), hemoglobin (HGB), platelets (PLT), absolute neutrophil count (ANC), alanine transaminase (ALT), aspartate aminotransferase (AST), creatinine(Cr), and blood urea nitrogen (BUN). CONCLUSIONS: The use of ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation is safe for CINV patients, and can effectively relieve nausea and vomiting and alleviate digestive symptoms.

Efficient computational model of the in-flow capturing of magnetic nanoparticles by a cylindrical magnet for cancer nanomedicine.

Magnetic nanoparticles have emerged as a promising approach to improving cancer treatment. However, many nanoparticle designs fail in clinical trials due to a lack of understanding of how to overcome the in vivo transport barriers. To address this shortcoming, we develop a computational model aimed at the study of magnetic nanoparticles in vitro and in vivo. In this paper, we present an important building block for this overall goal, namely an efficient computational model of the in-flow capture of magnetic nanoparticles by a cylindrical permanent magnet in an idealized test setup. We use a continuum approach based on the Smoluchowski advection-diffusion equation, combined with a simple approach to consider the capture at an impenetrable boundary, and derive an analytical expression for the magnetic force of a cylindrical magnet of finite length on the nanoparticles. This provides a simple and numerically efficient way to study different magnet configurations and their influence on the nanoparticle distribution in three dimensions. Such an in silico model can increase insight into the underlying physics, help to design prototypes, and serve as a precursor to more complex systems in vivo and in silico.

G protein-coupled receptor-mediated signaling of immunomodulation in tumor progression.

G protein-coupled receptors (GPCRs) are essential contributors to tumor growth and metastasis due to their roles in immune cell regulation. Therefore, GPCRs are potential targets for cancer immunotherapy. Here, we discuss the current understanding of the roles of GPCRs and their signaling pathways in tumor progression from an immunocellular perspective. Additionally, we focus on the roles of GPCRs in regulating immune checkpoint proteins involved in immune evasion. Finally, we review the progress of clinical trials of GPCR-targeted drugs for cancer treatment, which may be combined with immunotherapy to improve treatment efficacy. This expanded understanding of the role of GPCRs may shed light on the mechanisms underlying tumor progression and provide a novel perspective on cancer immunotherapy.

Therapeutic potential of twenty-first century music for cancer survivorship: from music and conceptual metaphor perspectives to a synergetic effect approach.

This paper examines the therapeutic potential of twenty-first century music as a means of supplementary therapeutic care for cancer survivorship. It presents a study of songs by Rihanna, Beyoncé, Adele, Coldplay, and Imagine Dragons, which combines the analysis of relevant music features and conceptual metaphors in the lyrics to examine the effect of the songs on the audience. The main aim of this study was to highlight the emotional and cognitive impact of these songs on listeners and identify their potential role in improving the psychological condition of patients with cancer who are downtrodden or reeling from the pain of surgery, chemotherapy, and side effects of treatment. This article adopts the conceptual metaphorical framework proposed by Lakoff and Johnson (1980) and the metaphor identification procedure (MIP) (Pragglejazz group, 2007) to examine the targeted use of metaphors features in the lyrics of the selected songs. The findings show that although there is a therapeutic potential associated with the songs analyzed, there are also potential risks for patients with cancer. "".

What does "urgency" mean when prioritizing cancer treatment? Results from a qualitative study with German oncologists and other experts during the COVID-19 pandemic.

PURPOSE: Cancer care in Germany during the COVID-19 pandemic was affected by resource scarcity and the necessity to prioritize medical measures. This study explores ethical criteria for prioritization and their application in cancer practices from the perspective of German oncologists and other experts. METHODS: We conducted fourteen semi-structured interviews with German oncologists between February and July 2021 and fed findings of interviews and additional data on prioritizing cancer care into four structured group discussions, in January and February 2022, with 22 experts from medicine, nursing, law, ethics, health services research and health insurance. Interviews and group discussions were digitally recorded, transcribed verbatim and analyzed using qualitative content analysis. RESULTS: Narratives of the participants focus on "urgency" as most acceptable criterion for prioritization in cancer care. Patients who are considered curable and those with a high level of suffering, were given a high degree of "urgency." However, further analysis indicates that the "urgency" criterion needs to be further distinguished according to at least three different dimensions: "urgency" to (1) prevent imminent harm to life, (2) prevent future harm to life and (3) alleviate suffering. In addition, "urgency" is modulated by the "success," which can be reached by means of an intervention, and the "likelihood" of reaching that success. CONCLUSION: Our analysis indicates that while "urgency" is a well-established criterion, its operationalization in the context of oncology is challenging. We argue that combined conceptual and clinical analyses are necessary for a sound application of the "urgency" criterion to prioritization in cancer care.