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Ruth Plummer,1 Alastair Greystoke,1 Gregory Naylor,2 Debashis Sarker,3,4 ANM Kaiser Anam,4 Hans Prenen,5 Laure-Anne Teuwen,5 Eric Van Cutsem,6 Jeroen Dekervel,6 Beate Haugk,1 Thomas Ness,1 Sujata Bhoi,7 Malene Jensen,7 Tom Morris,7 Pia Baumann,7 Niclas Sjögren,8 Karin Tunblad,7 Hans Wallberg,7 Fredrik Öberg,7 Thomas R Jeffry Evans2 1Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK; 2Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, UK; 3School of Cancer and Pharmaceutical Sciences, King’s College London, London, UK; 4Department of Medical Oncology, Guy’s Hospital, London, UK; 5Department of Oncology, Antwerp University Hospital, Edegem, Belgium; 6Department of Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium; 7Medivir AB, Huddinge, Sweden; 8SDS Life Science, Stockholm, SwedenCorrespondence: Pia Baumann, Medivir AB, Box 1086, SE-141 22, Huddinge, Sweden, Tel +46 739163897, Email pia.baumann@medivir.comPurpose: To evaluate safety, preliminary efficacy, pharmacokinetics, and pharmacodynamics, of fostroxacitabine bralpamide (fostrox, MIV-818), a novel oral troxacitabine nucleotide prodrug designed to direct exposure to the liver, while minimizing systemic toxicity.Patients and Methods: Fostrox monotherapy was administered in an open-label, single-arm, first-in-human, phase 1a/1b study, in patients with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma, or solid tumor liver metastases. The first part (1a) consisted of intra/inter-patient escalating doses (3 mg to 70 mg) QD for up to 5 days, and the second part (1b), doses of 40 mg QD for 5 days, in 21-day cycles. Safety and tolerability were evaluated by the Safety Review Committee, and efficacy was assessed every 6 weeks with CT or MRI using RECIST 1.1 and mRECIST.Results: Nineteen patients were treated with fostrox. Most common adverse events (AEs) were hematological and increased AST. Grade 3 treatment related AEs (TRAE) were seen in 53% of the patients, with transient neutropenia and thrombocytopenia as the most common. No grade 5 AE was observed. Recommended Phase 2 dose of fostrox was 40 mg QD for 5 days in 21-day cycles. Preliminary efficacy showed a clinical benefit rate in the liver of 53% and stable disease (SD) as best response in 10 patients. Liver targeting with fostrox was confirmed with higher exposure of troxacitabine and its metabolites in liver compared to plasma. Systemic exposure of fostrox was generally low with troxacitabine as main analyte. Biopsies demonstrated tumor-selective, drug-induced DNA damage.Conclusion: The phase 1a/1b monotherapy study of fostrox, in patients with liver tumors, showed a tumor selective effect in the liver and that 40 mg QD for 5 days in 21-day cycles is safe and tolerable. Safety and preliminary efficacy in patients with advanced HCC supports clinical development of fostrox in combination with other modes of action in HCC.Keywords: phase 1, fostrox, hepatocellular carcinoma, nucleotide prodrug, pharmacokinetics, pharmacodynamics

Background & Aims: Two recently developed composite models, the alpha-fetoprotein (AFP) score and Metroticket 2.0, could be used to select patients with hepatocellular carcinoma (HCC) who are candidates for liver transplantation (LT). The aim of this study was to compare the predictive performance of both models and to evaluate the net risk reclassification of post-LT recurrence between them using each model’s original thresholds. Methods: This multicenter cohort study included 2,444 adult patients who underwent LT for HCC in 47 centers from Europe and Latin America. A competing risk regression analysis estimating sub-distribution hazard ratios (SHRs) and 95% CIs for recurrence was used (Fine and Gray method). Harrell’s adapted c-statistics were estimated. The net reclassification index for recurrence was compared based on each model’s original thresholds. Results: During a median follow-up of 3.8 years, there were 310 recurrences and 496 competing events (20.3%). Both models predicted recurrence, HCC survival and survival better than Milan criteria (p

Background & Aims: Patients with hepatocellular carcinoma (HCC) are selected for liver transplantation (LT) based on pre-LT imaging ± alpha-foetoprotein (AFP) level, but discrepancies between pre-LT tumour assessment and explant are frequent. Our aim was to design an explant-based recurrence risk reassessment score to refine prediction of recurrence after LT and provide a framework to guide post-LT management. Methods: Adult patients who underwent transplantation between 2000 and 2018 for HCC in 47 centres were included. A prediction model for recurrence was developed using competing-risk regression analysis in a European training cohort (TC; n = 1,359) and tested in a Latin American validation cohort (VC; n=1,085). Results: In the TC, 76.4% of patients with HCC met the Milan criteria, and 89.9% had an AFP score of ≤2 points. The recurrence risk reassessment (R3)-AFP model was designed based on variables independently associated with recurrence in the TC (with associated weights): ≥4 nodules (sub-distribution of hazard ratio [SHR] = 1.88, 1 point), size of largest nodule (3–6 cm: SHR = 1.83, 1 point; >6 cm: SHR = 5.82, 5 points), presence of microvascular invasion (MVI; SHR = 2.69, 2 points), nuclear grade >II (SHR = 1.20, 1 point), and last pre-LT AFP value (101–1,000 ng/ml: SHR = 1.57, 1 point; >1,000 ng/ml: SHR = 2.83, 2 points). Wolber’s c-index was 0.76 (95% CI 0.72–0.80), significantly superior to an R3 model without AFP (0.75; 95% CI 0.72–0.79; p = 0.01). Four 5-year recurrence risk categories were identified: very low (score = 0; 5.5%), low (1–2 points; 15.1%), high (3–6 points; 39.1%), and very high (>6 points; 73.9%). The R3-AFP score performed well in the VC (Wolber’s c-index of 0.78; 95% CI 0.73–0.83). Conclusions: The R3 score including the last pre-LT AFP value (R3-AFP score) provides a user-friendly, standardised framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials for HCC not limited to the Milan criteria. Clinical Trials Registration: NCT03775863. Lay summary: Considering discrepancies between pre-LT tumour assessment and explant are frequent, reassessing the risk of recurrence after LT is critical to further refine the management of patients with HCC. In a large and international cohort of patients who underwent transplantation for HCC, we designed and validated the R3-AFP model based on variables independently associated with recurrence post-LT (number of nodules, size of largest nodule, presence of MVI, nuclear grade, and last pre-LT AFP value). The R3-AFP model including last available pre-LT AFP value outperformed the original R3 model only based on explant features. The final R3-AFP scoring system provides a robust framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials, irrespective of criteria used to select patients with HCC for LT.

Background & Aims: Good outcomes after liver transplantation (LT) have been reported after successfully downstaging to Milan criteria in more advanced hepatocellular carcinoma (HCC). We aimed to compare post-LT outcomes in patients receiving locoregional therapies (LRT) before LT according to Milan criteria and University of California San Francisco downstaging (UCSF-DS) protocol and ‘all-comers’. Methods: This multicentre cohort study included patients who received any LRT before LT from Europe and Latin America (2000–2018). We excluded patients with alpha-foetoprotein (AFP) above 1,000 ng/ml. Competing risk regression analysis for HCC recurrence was conducted, estimating subdistribution hazard ratios (SHRs) and corresponding 95% CIs. Results: From 2,441 LT patients, 70.1% received LRT before LT (n = 1,711). Of these, 80.6% were within Milan, 12.0% within UCSF-DS, and 7.4% all-comers. Successful downstaging was achieved in 45.2% (CI 34.8–55.8) and 38.2% (CI 25.4–52.3) of the UCSF-DS group and all-comers, respectively. The risk of recurrence was higher for all-comers (SHR 6.01 [p

Purpose: To evaluate the outcomes of resin-based yttrium-90 radioembolization (TARE) for hepatocellular carcinoma (HCC) as a bridging or downstaging therapy to liver transplantation (LT) in terms of safety, tumor response, recurrence, and survival., Materials & Methods: A single-center retrospective analysis of patients with HCC treated with resin-based TARE as bridging or downstaging treatment to LT between January 2006 and April 2021 was performed. TARE-related liver toxicity was assessed. Imaging data were analyzed to assess tumor response. Histopathological analysis of explant livers was performed to assess HCC necrosis. Survival and bridging/downstaging success predictor analysis was performed., Results: Thirty-six patients underwent resin-based TARE with the intention to bridge (33%) or downstage (67%) to LT. 44% had ≥3 HCC lesions, 53% had bilobar disease. Median largest tumor diameter was 3.4 cm. TARE was segmental, lobar, and bilobar in 20%, 36%, and 44% of cases, respectively. 17% had grade 3 bilirubin toxicities. Objective response rate per mRECIST was 72%. Patients meeting UNOS-DS criteria had higher chances of successful bridging/downstaging. 23 patients were transplanted. Complete pathologic response was seen in 30% of explant livers. Post-transplant tumor recurrence occurred in 26% within a median follow-up period of 1710 days. Estimated 5-year progression-free, disease-specific, and overall survival rates after LT were 89%, 69%, and 89%, respectively. For the entire patient cohort, these rates were 87%, 53% and 70%., Conclusion: Resin-based 90 Y TARE can be considered a valuable treatment option for bridging or downstaging patients with HCC to LT, including patients requiring (bi-)lobar TARE for extensive tumoral disease., (Copyright © 2024. Published by Elsevier Inc.)

Background: In the TOPAZ-1, patients with biliary tract cancers (BTC) and recurrence within 6 months after surgery were excluded, even if this event is frequently observed in clinical practice. Our study aimed to assess if the efficacy of cisplatin-gemcitabine-durvalumab (CGD) in this population is comparable to that reported in the phase 3 trial., Methods: The study cohort included patients with BTC who underwent surgery on the primary tumor, experienced disease recurrence occurring ≤6 months or >6 months after surgery or after the end of adjuvant therapy and started CGD. The primary objectives were overall survival (OS) and progression free survival (PFS)., Results: A total of 178 patients were enrolled. No significant differences were observed between early and late relapse groups in OS (23.4 months vs not reached; HR 1.26; 95% CI, 0.67-2.37; P = .45) and PFS [7.0 months vs 9.8 months; HR 1.3(95% CI, 0.9-2.1) P = .13]. Overall response rate and disease control rate (P = .33 and P = .62) were comparable between the 2 groups, as the overall safety profile. In addition, we compared survival outcomes between the selected population and a historical cohort of patients with BTC treated with cisplatin-gemcitabine (CG) and found that despite the absence of statistical significance, CGD showed an outcome trend compared with CG regardless of the time of recurrence after surgery or adjuvant chemotherapy [(CG ≤ 6 vs CGD ≤ 6 months: HR 0.59, 95%CI, 0.35-1.01, P = .05; HR 0.70; 95%CI, 0.46-1.06, P = .09, OS and PFS, respectively) and (CG > 6 vs. CGD > 6 months: HR 0.50; 95%CI, 0.29-0.88, P = 0.0165; HR 0.54; 95%CI, 0.35-0.84, P = .0068, OS and PFS, respectively)]., Conclusion: Our analysis suggests that CGD retains its efficacy independently of the timing of relapse after surgery or completion of adjuvant treatment in patients with advanced BTC., (© The Author(s) 2024. Published by Oxford University Press.)

Case series describing excellent outcomes for patients with dMMR GI cancer after resection of a single progressive lesion under immunotherapy.

Background & Aims: Transforming growth factor β (TGF-β) plays an oncogenic role in advanced cancer by promoting cell proliferation, metastasis and immunosuppression. PMEPA1 (prostate transmembrane protein androgen induced 1) has been shown to promote TGF-β oncogenic effects in other tumour types. Thus, we aimed to explore the role of PMEPA1 in hepatocellular carcinoma (HCC)., Methods: We analysed 1,097 tumours from patients with HCC, including discovery (n = 228) and validation (n = 361) cohorts with genomic and clinicopathological data. PMEPA1 levels were assessed by qPCR (n = 228), gene expression data (n = 869) and at the single-cell level (n = 54). Genetically engineered mouse models overexpressing MYC+PMEPA1 compared to MYC were generated and molecular analyses were performed on the HCCs obtained., Results: PMEPA1 was overexpressed in 18% of HCC samples (fold-change >2; n = 201/1,097), a feature associated with TGF-β signalling activation ( p < 0.05) and absence of gene body hypomethylation ( p < 0.01). HCCs showing both TGF-β signalling and high PMEPA1 levels (12% of cases) were linked to immune exhaustion, late TGF-β activation, aggressiveness and higher recurrence rates after resection, in contrast to HCCs with only TGF-β signalling (8%) or PMEPA1 overexpression (9%). Single-cell RNA sequencing analysis identified PMEPA1 expression in HCC and stromal cells. PMEPA1 -expressing tumoural cells were predicted to interact with CD4 + regulatory T cells and CD4 + CXCL13 + and CD8 + exhausted T cells. In vivo , overexpression of MYC + PMEPA1 led to HCC development in ∼60% of mice and a decreased survival compared to mice overexpressing MYC alone ( p = 0.014). MYC + PMEPA1 tumours were enriched in TGF-β signalling, paralleling our human data., Conclusions: In human HCC, PMEPA1 upregulation is linked to TGF-β activation, immune exhaustion, and an aggressive phenotype. Overexpression of PMEPA1+MYC led to tumoural development in vivo , demonstrating the oncogenic role of PMEPA1 in HCC for the first time., Impact and Implications: PMEPA1 can enhance the tumour-promoting effects of TGF-β in cancer. In this study, we demonstrate that PMEPA1 is highly expressed in ∼18% of patients with hepatocellular carcinoma (HCC), a feature associated with poor prognosis, TGF-β activation and exhaustion of immune cells. Similarly, in mouse models, PMEPA1 overexpression promotes HCC development, which demonstrates its oncogenic role. The identification of PMEPA1 as oncogenic driver in HCC and its role in immune exhaustion and poor clinical outcomes enhances our understanding of HCC pathogenesis and opens new avenues for targeted therapeutic interventions., (© 2024 The Authors.)

Background: The TOPAZ-1 phase III trial showed a survival benefit with durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). To understand this combination's real-world efficacy and tolerability, we conducted a global multicenter retrospective analysis of its first-line treatment outcomes., Methods: We included patients with unresectable, locally advanced, or metastatic BTC treated with durvalumab, gemcitabine, and cisplatin at 39 sites in 11 countries (Europe, the United States, and Asia). The primary endpoint was overall survival (OS)., Results: 666 patients were enrolled. Median OS was 15.1 months and median PFS was 8.2 months. The investigator-assessed overall response rate was 32.7 %, with stable disease in 45.2 % of patients. High baseline CEA levels, ECOG PS > 0, metastatic disease, and NLR > 3 were associated with poor survival. Any grade adverse events (AEs) occurred in 92.9 % of patients (grade >2: 46.6 %). Immune-related AEs (irAEs) occurred in 20.0 % (grade >2: 2.5 %). Three deaths (0.5 %) were deemed treatment-related, none linked to immunotherapy. Common irAEs were rash (8.2 % all grades; 0.3 % grade >2), itching (10.3 % all grades; 0.2 % grade >2), and hypothyroidism (5.1 % all grades; 0.3 % grade >2). Durvalumab discontinuation rate due to AEs was 1.5 %. ESMO-recommended genes were analyzed and no outcome differences were found. A comparative analysis with a historical cohort of patients treated with chemotherapy alone confirmed the positive survival impact of durvalumab in combination with cisplatin/gemcitabine., Conclusion: This first global real-world analysis largely confirmed the TOPAZ-1 findings, supporting gemcitabine, cisplatin, and durvalumab as a first-line standard of care for patients with advanced BTC., Competing Interests: Declaration of Competing Interest LR reports consulting fees from AbbVie, AstraZeneca, Basilea, Bayer, Elevar Therapeutics, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Jazz Pharmaceuticals, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology, Zymeworks; lecture fees from AstraZeneca, Bayer, BMS, Incyte, Ipsen, Roche, Servier; travel expenses from AstraZeneca; research grants (to Institution) from Agios, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Servier, Zymeworks. ACG reports consulting fees from AstraZeneca, Bayer, BMS, Eisai, Incyte, Ipsen, IQVIA, MSD, Roche, Servier; lecture fees from AstraZeneca, Bayer, BMS, Eisai, Incyte, Ipsen, Roche, Servier; travel expenses from AstraZeneca; research grants (to Institution) from AstraZeneca, Eisai. SLC serves an advisory member for AstraZeneca, MSD, Eisai, BMS, Ipsen, and Hengrui, received research funds from MSD, Eisai, Ipsen, SIRTEX, and Zailab, and honoraria from AstraZeneca, Eisai, Roche, Ipsen, and MSD. TP received consulting fees from Bayer, Ipsen, and AstraZeneca; institutional research funding from Roche, Bayer, and AstraZeneca; travel expenses from Roche. CB received honoraria as speaker (Astrazeneca, Incyte, Servier) and consultant (Incyte, Servier, Boehringer Ingelheim, Astrazeneca), received research funds (Avacta, Medannex, Servier) and her spouse is an employee of Astrazeneca. M. Ikeda reports honoraria from AstraZeneca, Chugai Pharma, Eisai, Incyte, Lilly Japan, MSD, Novartis, Ono Pharmaceutical, Takeda, Teijin Pharma, Nihon Servier, Taiho and research funding from AstraZeneca, Bayer, Bristol-Myers Squibb, Chiome Bioscience, Chugai, Eisai, Eli Lilly Japan, Delta-Fly Pharma, Invitae, J-Pharma, Merck biopharma, Merus N.V., MSD, Novartis, Nihon Servier, Ono, Syneos Health, and Rakuten Medical. GWP: Advisories and/or Speaker fees: Servier, Bayer, Roche Amgen, Merck, MSD, BMS, Sanofi, Lilly, Astra Zeneca, Astellas, Pierre-Fabre, Incyte, Arcus, CECOG. F. F. has received travel support from Ipsen, Abbvie, Astrazeneca and speaker’s fees from AbbVie, MSD, Ipsen, Astrazeneca. LP: Advisory role: AstraZeneca, Servier, Travel expenses: AstraZeneca, Ipsen. GG: Consulting Fees: Astra Zeneca, MSD, Servier, Seagen, Bayer, Amgen, Novartis, Ipsen, BMS. Travel Expenses: Astra Zeneca, Servier, Bayer, Novartis. S.L. reports research funding (to Institution) from Amgen, Astellas, Astra Zeneca, Bayer, Bristol-Myers Squibb, Daichii Sankyo, Hutchinson, Incyte, Merck Serono, Mirati, MSD, Pfizer, Roche, Servier; personal honoraria as invited speaker from Amgen, Astra Zeneca, Bristol-Myers Squibb, Incyte, GSK, Lilly, Merck Serono, MSD, Pierre-Fabre, Roche, Servier; participation in advisory board for Amgen, Astellas, Astra Zeneca, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, GSK, Incyte, Lilly, Merck Serono, MSD, Servier, Takeda, Rottapharm. JD received consulting fees and/or speaker honoraria from Amgen, AstraZeneca, Bayer, BMS, Eisai, Need Inc., Ipsen, Lilly, MediMix, Merck, MSD, Novartis, Roche and Servier. All remaining authors have declared no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

[ 18 F]AlF-NOTA-octreotide ([ 18 F]AlF-OC) is a promising alternative for [ 68 Ga]Ga-DOTA-somatostatin analogs (SSAs) in positron emission tomography (PET) imaging of the somatostatin receptor (SSTR). Our aim is to assess changes in TNM staging and differences in patient management between [ 18 F]AlF-OC PET/CT and [ 68 Ga]Ga-DOTA-SSA PET/CT in the work-up of neuroendocrine tumor (NET) patients. Patients who underwent both [ 18 F]AlF-OC and [ 68 Ga]Ga-DOTA-TATE or [ 68 Ga]Ga-DOTA-NOC PET/CT in our multicenter study (Pauwels et al., J Nucl Med.2023;63:632-638) with a NET were included for analysis. TNM staging was determined and compared for both tracers. For each patient, the blinded [ 68 Ga]Ga-DOTA-SSA or [ 18 F]AlF-OC PET/CT images were presented in random order at a multidisciplinary team board. The images were presented together with clinical information and compared with previous SSTR and [ 18 F]FDG PET/CT imaging. After a consensus decision for patient management was recorded, the board was presented with the PET/CT images from the other SSTR tracer and a decision was made for the second tracer. Differences in management were classified as major if it entailed an intermodality change and minor if it led to an intramodality change. Compared with [ 68 Ga]Ga-DOTA-SSA, the use of [ 18 F]AlF-OC led to a change in 16/75 patients: TNM staging changes in 10/75 patients (13.3%; downstaging in 3/10, upstaging in 7/10) and differences in clinical management were seen in 10/75 patients (13.3%), leading to a major difference in 7/10 cases and a minor change in 3/10 cases. All 10 cases with a difference in patient management between both PET tracers were caused by additional lesion detection by [ 18 F]AlF-OC. The use of [ 18 F]AlF-OC did not impact TNM staging or clinical management in the large majority of the patients (86.7%), further validating the potential for routine clinical use of [ 18 F]AlF-OC PET/CT as an alternative for [ 68 Ga]Ga-DOTA-SSA PET/CT. The trial is registered under ClinicalTrials.gov identifier NCT04552847 and EudraCT 2020-000549-15., (© 2024 British Society for Neuroendocrinology.)

Competing Interests: Disclosure The authors have stated that they have no conflicts of interest.

Lynch syndrome (LS) and constitutional mismatch repair deficiency (CMMRD) are distinct cancer syndromes caused, respectively, by mono- and bi-allelic germline mismatch repair (MMR) variants. LS predisposes to mainly gastrointestinal and genitourinary cancers in adulthood. CMMRD predisposes to brain, haematological, and LS-spectrum cancers from childhood. Two suspected LS patients with first cancer diagnosis aged 27 or 38 years were found to be homozygous for an MMR (likely) pathogenic variant, MSH6 c.3226C>T (p.(Arg1076Cys)), or variant of uncertain significance (VUS), MLH1 c.306G>A (p.(Glu102=)). MLH1 c.306G>A was shown to cause leaky exon 3 skipping. The apparent genotype-phenotype conflict was resolved by detection of constitutional microsatellite instability in both patients, a hallmark feature of CMMRD. A hypomorphic effect of these and other variants found in additional late onset CMMRD cases, identified by literature review, likely explains a LS-like phenotype. CMMRD testing in carriers of compound heterozygous or homozygous MMR VUS may find similar cases and novel hypomorphic variants. Individualised management of mono- and bi-allelic carriers of hypomorphic MMR variants is needed until we better characterise the associated phenotypes., (© 2024. The Author(s).)

Primary liver cancer, more specifically hepatocellular carcinoma (HCC), remains a significant global health problem associated with increasing incidence and mortality. Clinical, biological, and molecular heterogeneity are well-known hallmarks of cancer and HCC is considered one of the most heterogeneous tumour types, displaying substantial inter-patient, intertumoural and intratumoural variability. This heterogeneity plays a pivotal role in hepatocarcinogenesis, metastasis, relapse and drug response or resistance. Unimodal single-cell sequencing techniques have already revolutionised our understanding of the different layers of molecular hierarchy in the tumour microenvironment of HCC. By highlighting the cellular heterogeneity and the intricate interactions among cancer, immune and stromal cells before and during treatment, these techniques have contributed to a deeper comprehension of tumour clonality, hematogenous spreading and the mechanisms of action of immune checkpoint inhibitors. However, major questions remain to be elucidated, with the identification of biomarkers predicting response or resistance to immunotherapy-based regimens representing an important unmet clinical need. Although the application of single-cell multi-omics in liver cancer research has been limited thus far, a revolution of individualised care for patients with HCC will only be possible by integrating various unimodal methods into multi-omics methodologies at the single-cell resolution. In this review, we will highlight the different established single-cell sequencing techniques and explore their biological and clinical impact on liver cancer research, while casting a glance at the future role of multi-omics in this dynamic and rapidly evolving field., Competing Interests: The authors of this study declare that they do not have any conflict of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2024 The Author(s).)