Cancer Surveillance Research Articles

Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trials.

In non-small cell lung cancers, the non-squamous and squamous subtypes (nsqNSCLC and sqNSCLC) exhibit disparities in pathophysiology, tumor immunology, and potential genomic correlates affecting responses to immune checkpoint inhibitor (ICI)-based treatments. In our in-house training cohort (n=85), the presence of the LRP1B deleterious mutation (LRP1B-del) was associated with longer and shorter progression-free survival (PFS) on ICIs alone in nsqNSCLCs and sqNSCLCs, respectively (Pinteraction=0.008). These results were validated using a larger public ICI cohort (n=208, Pinteraction<0.001). Multiplex immunofluorescence staining revealed an association between LRP1B-del and increased and decreased numbers of tumor-infiltrating CD8+ T cells in nsqNSCLCs (P=0.040) and sqNSCLCs (P=0.014), respectively. In the POPLAR/OAK cohort, nsqNSCLCs with LRP1B-del demonstrated improved PFS benefits from atezolizumab over docetaxel (hazard ratio (HR) =0.70, P=0.046), whereas this benefit was negligible in those without LRP1B-del (HR=1.05, P=0.64). Conversely, sqNSCLCs without LRP1B-del benefited more from atezolizumab (HR=0.60, P=0.002) than those with LRP1B-del (HR=1.30, P=0.31). Consistent results were observed in the in-house CHOICE-01 cohort, in which nsqNSCLCs with LRP1B-del and sqNSCLCs without LRP1B-del benefited more from toripalimab plus chemotherapy than from chemotherapy alone (Pinteraction=0.008). This multi-cohort study delineates the antithetical impacts of LRP1B-del in nsqNSCLCs and sqNSCLCs on predicting the benefits from ICI alone or with chemotherapy over chemotherapy alone. Our findings highlight the distinct clinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs, emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.

Survival associated with the use of sentinel lymph node in addition to lymphadenectomy in early-stage cervical cancer treated with surgery alone: A sub-analysis of the Surveillance in Cervical CANcer (SCCAN) collaborative study

AimThe aim of this study was to assess whether the use of sentinel lymph node (SLN) in addition to lymphadenectomy was associated with survival benefit in patients with early-stage cervical cancer. MethodsInternational, multicenter, retrospective study. Inclusion criteria: cervical cancer treated between 01/2007 and 12/2016 by surgery only; squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, FIGO 2009 stage IB1-IIA2, negative surgical margins, and laparotomy approach. Patients undergoing neo-adjuvant and/or adjuvant treatment and/or with positive para-aortic lymph nodes, were excluded. Women with positive pelvic nodes who refused adjuvant treatment, were included. Lymph node assessment was performed by SLN (with ultrastaging protocol) plus pelvic lymphadenectomy (‘SLN’ group) or pelvic lymphadenectomy alone (‘non-SLN’ group). Results1083 patients were included: 300 (27.7 %) in SLN and 783 (72.3 %) in non-SLN group. 77 (7.1 %) patients had recurrence (N = 11, 3.7 % SLN versus N = 66, 8.4 % non-SLN, p = 0.005) and 34 (3.1 %) (N = 4, 1.3 % SLN versus N = 30, 3.8 % non-SLN, p = 0.033) died. SLN group had better 5-year disease-free survival (DFS) (96.0 %,95 %CI:93.5–98.5 versus 92.0 %,95 %CI:90.0–94.0; p = 0.024). No 5-year overall survival (OS) difference was shown (98.4 %,95 %CI:96.8–99.9 versus 96.8 %,95 %CI:95.4–98.2; p = 0.160). SLN biopsy and lower stage were independent factors associated with improved DFS (HR:0.505,95 %CI:0.266–0.959, p = 0.037 and HR:2.703,95 %CI:1.389–5.261, p = 0.003, respectively). Incidence of pelvic central recurrences was higher in the non-SLN group (1.7 % versus 4.5 %, p = 0.039). ConclusionAdding SLN biopsy to pelvic lymphadenectomy was associated with lower recurrence and death rate and improved 5-year DFS. This might be explained by the lower rate of missed nodal metastasis thanks to the use of SLN ultrastaging. SLN biopsy should be recommended in patients with early-stage cervical cancer.

Is End-Stage Renal Disease Tumor Suppressive? Dispelling the Myths.

The prevalence of end-stage renal disease is increasing worldwide. Malignancies accompanying end-stage renal disease are detected in approximately 120 individuals per 10,000 person-years. Most studies have suggested that end-stage renal disease causes carcinogenesis and promotes tumor development; however, this theory remains questionable. Contrary to the theory that end-stage renal disease is predominantly carcinogenic, recent findings have suggested that after controlling for biases and sampling errors, the overall cancer risk in patients with end-stage renal disease might be lower than that in the general population, except for renal and urothelial cancer risks. Additionally, mortality rates associated with most cancers are lower in patients with end-stage renal disease than in the general population. Several biological mechanisms have been proposed to explain the anticancer effects of end-stage renal disease, including premature aging and senescence, enhanced cancer immunity, uremic tumoricidal effects, hormonal and metabolic changes, and dialysis therapy-related factors. Despite common beliefs that end-stage renal disease exacerbates cancer risk, emerging evidence suggests potential tumor-suppressive effects. This review highlights the potential anticancer effects of end-stage renal disease, proposing reconsideration of the hypothesis that end-stage renal disease promotes cancer development and progression.

Pleiotropy of biomineralized bacterial outer membrane vesicles in modulating immune systems for liver cancer therapy

The immune landscape of late-stage liver cancer is featured by severe immunosuppression that is characterized by poor immunogenicity, T-cell exhaustion, and infiltration of a large number of immunosuppressive cells, leading to compromised therapeutic efficacy of mainstream immunotherapies. Herein, we developed a pleiotropic immune cell mobilization strategy to modulate immune systems for immunosuppressive liver cancer therapy. In this study, immunogenic bacteria-derived outer membrane vesicles (OMVs) were exploited as a vector to deposit Cu and Mn with mixed valence states via one-step biomineralization, followed by platelet membrane camouflage, which are denoted as OPCM. Mechanistically, the pleiotropic OPCM possesses POD, CAT, and GPX-like activities, thereby achieving cGAS-STING activation, immunogenic ferroptosis, and tumor hypoxia alleviation, ultimately leading to initiation of the cancer immunity cycle, modulation of both innate and adaptive immune system, and reversion of immunosuppression. Notably, the combination with typical αPD-L1 treatment augmented the tumor suppression effect by amplifying the intensity of ferroptosis due to IFN-γ secretion by activated T cells. Overall, the metal biomineralized OPCMs in combination with αPD-L1 formed a closed-loop therapy that cycles from immunotherapy and ferroptosis therapy, providing new insights for treating immunosuppressive liver cancer.

Gut Microbiota-Related Biomarkers in Immuno-Oncology.

Carcinogenesis is associated with the emergence of protracted intestinal dysbiosis and metabolic changes. Increasing evidence shows that gut microbiota-related biomarkers and microbiota-centered interventions are promising strategies to overcome resistance to immunotherapy. However, current standard methods for evaluating gut microbiota composition are cost- and time-consuming. The development of routine diagnostic tools for intestinal barrier alterations and dysbiosis constitutes a critical unmet medical need that can guide routine treatment and microbiota-centered intervention decisions in patients with cancer. In this review, we explore the influence of gut microbiota on cancer immunotherapy and highlight gut-associated biomarkers that have the potential to be transformed into simple diagnostic tools, thus guiding standard treatment decisions in the field of immuno-oncology. Mechanistic insights toward leveraging the complex relationship between cancer immunosurveillance, gut microbiota, and metabolism open exciting opportunities for developing novel biomarkers in immuno-oncology.

N6-methyladenosine (m6A) writer METTL5 represses the ferroptosis and antitumor immunity of gastric cancer

Emerging evidence has shown that ferroptosis and antitumor immunity response of T lymphocytes play critical roles in multiple malignancies, including gastric cancer (GC). Here, the present research aims to reveal the function of novel N6-methyladenosine (m6A) methyltransferase METTL5 on GC immune microenvironment. Clinically, elevated METTL5 was negatively correlated to the prognosis of GC patients. METTL5 high-expression repressed the Fe2+ accumulation and ferroptosis to promote the GC immune evasion escaping from activated PBMCs’ killing effect. Mechanistically, upregulation of METTL5 promoted NRF2 mRNA stability, thereby inactivating the ferroptosis and repressing PBMCs’ cells antitumor immunity. One valuable finding is that ferroptosis inhibitor (Ferrostatin-1, Fer-1) could reduce the antitumor immunity of cocultured PBMCs. In other words, the increase of ferroptosis might contribute to the anti-tumor efficacy of immunotherapy. Further study revealed that m6A reader IGF2BP1 mediated the stability of NRF2 mRNA via METTL5/m6A/NRF2 axis. Collectively, these results demonstrate that METTL5 functions as an oncogene in GC immune microenvironment, and highlights a critical role in T lymphocytes’ antitumor immunity.

ZFP1 is a biomarker related to poor prognosis and immunity in gastric cancer

We aimed to determine the prognostic significance of ZFP1 in gastric cancer (GC), its role in the immune microenvironment, and its potential as a therapeutic target using data from The Cancer Genome Atlas (TCGA) database. ZFP1 overexpression was closely associated with tumour T stage and histological grade. Patients with GC and high ZFP1 expression had poor outcomes. Lower ZFP1 expression was associated with longer symptom-free intervals and disease-specific survival. Subgroup analyses of T3 and T4, N0, N1, and M0 patients showed that overall survival (OS), disease-specific survival, and progression-free interval (PFI) were worse in those with high ZFP1 expression. ZFP1 expression in GC was moderately to strongly positively correlated with the infiltration levels of effector central memory T cells and T helper cells and negatively correlated with Th17 cells and NK CD56bright cells. The lncRNA-miRNA-ZFP1 axis was predicted using a public database. CCK8, colony formation, and wound healing assays were conducted to investigate whether ZFP1 promoted the proliferation and migration of GC cells. Our study suggests that ZFP1 plays a key role in the prognosis, immune response, and progression of GC and is a significant factor in the diagnosis and treatment of this disease.

ZG16 enhances the maturation of dendritic cells via induction of CD40 and contributes to the antitumor immunity in pancreatic cancer.

Dendritic cells (DCs) are critical mediators of antigen priming and T-cell activation. Zymogen granule protein 16 (ZG16) is demonstrated as an anti-oncogene in T-cell mediated antitumor immunity, but its effect on DCs is largely unknown. Herein, we wonder whether ZG16 affects the activation of DCs in pancreatic cancer. Firstly, the increased ZG16 expression was observed during the maturation of DCs derived from mouse bone marrow or human peripheral blood. Then, overexpression of ZG16 or exogenous introduction of recombinant ZG16 protein induced the expression of MHC II, CD86, CD84, and CCR7 on the surface of DCs, thereby facilitating the secretion of proinflammatory mediators IL-1β, IL-6, TNF-α, and IL-12/p70, supporting the promoting effect of ZG16 on DC maturation. By establishing the subcutaneous and orthotopic mouse models of pancreatic cancer, we confirmed that intraperitoneal injection of recombinant ZG16 protein (Re-mZG16) could induce tumor regression by stimulating DC maturation and enhancing antitumor responses of CD4 + , CD8 + , PD-1 + , and Ctla4+ cells. Besides, Re-mZG16 in combination with gemcitabine showed a synergistic effect in the treatment of pancreatic cancer. Mechanistically, we demonstrated that ZG16 inhibited the ubiquitination and degradation of CD40, which depended on the lectin domain of ZG16. In conclusion, this study provided a novel insight into the role of ZG16-CD40 axis in DC-based immunotherapy for pancreatic cancer.

Bayesian networks in modeling leucocyte interplay following brain irradiation: A comprehensive framework

Background and ObjectiveUnderstanding the intricate interactions among leucocyte subpopulations following radiotherapy is crucial for advancing cancer research and immunology. Recently, interest in recent radiotherapy modalities, such as protons, has increased. Herein, we present a framework utilizing Bayesian networks to uncover these complex relationships via an illustrative example of brain irradiation in rodents. MethodsWe utilized data from 96 healthy C57BL/6 adult mice subjected to either X-ray or proton brain irradiation. Leucocyte subpopulations in the blood collected 12 hours after the final irradiated fraction were quantified. We employed Bayesian networks to detect causal interplay between physiological parameters, radiation variables and circulating leucocytes. The causal structure was learned via the use of the Bayesian information criterion as a scored criterion. Parameter estimation was performed to quantify the strength of the identified causal relationships. Cross-validation was used to validate our Bayesian network model's performance. ResultsIn the X-ray model, we discovered previously undisclosed interactions between NK-cells and neutrophils, and between monocytes and T-CD4+ cells. The proton model revealed an interplay involving T-CD4+ cells and neutrophils. Both X-rays and protons led to heightened interactions between T-CD8+ cells and B cells, indicating their significant role in orchestrating immune responses. Additionally, the proton model displayed strengthened interactions between T-CD4+ and T-CD8+ cells, emphasizing a dynamic and coordinated immune response post-irradiation. Cross-validation results demonstrated the robustness of the Bayesian network model in explaining data uncertainty. ConclusionThe use of Bayesian networks as tools for causal structure discovery has revealed novel insights into the dynamics of immune responses to radiation exposure.

Conjunctival Melanoma: A Clinical Review and Update.

Conjunctival melanoma (Co-M) is an aggressive, invasive eye and eyelid cancer. Its global incidence of ~1 in a million is increasing at a rate ratio of ~1.4, but this rises sharply in over 65-year-olds. Although rare, Co-M has a devastating impact on the lives of those who develop it. Co-M is often misdiagnosed or overlooked, leading to vision loss either from the destructive effects of the tumour or side effects of therapy, facial disfigurement from radical surgery, and death from metastases. Due to its rarity, there is limited evidence for diagnosis and management; hence, there is no standardised treatment and not all cases are referred to a specialised ocular oncology centre. Recent progress in cancer immunology and genetics have revolutionised the treatment of cutaneous melanomas, which share some similarities to Co-M. Importantly, a better understanding of Co-M and its precursor lesions is urgently needed to lead to the development of novel targeted and immunotherapies both for local tumour control and disseminated disease. This review aims to provide a comprehensive clinical overview of the current knowledge regarding Co-M, its epidemiology, pathogenesis, presentation, diagnosis and recent changes in the classification of its precursor lesions, management, and recent advances in novel biological therapies for personalised treatment of this disease.

Trends in the incidence and mortality of cervical, ovarian, and corpus uteri cancers in Wales, UK: A joinpoint regression analysis from 2002 to 2021

ObjectivesThe primary objective of this study was to examine the secular trends of cervical, ovarian, and corpus uteri neoplasm in Wales, UK, over the period from 2002 to 2021. We aimed to identify changes in the incidence and mortality rates of these cancers to inform future healthcare policies and cancer prevention programs. MethodsWe sourced incidence data from 2002 to 2019 and mortality data from 2002 to 2021 from the Welsh Cancer Intelligence and Surveillance Unit. The data were analysed using Joinpoint regression to compute the average annual percentage change (AAPC) in age-standardized incidence rates (ASIR) and mortality rates (ASMR) per 100,000 population for each type of cancer. ResultsThe results showed that the ASIR for cervical cancer remained stable between 2002 and 2019 (AAPC = −0.5; 95 %CI = −1.4–0.4). However, the ASMR significantly declined from 4.88 in 2002–3.03 in 2021 (AAPC = −2.3; 95 %CI = −3.4 to −1.1). The ASIR for ovarian cancer significantly decreased from 27.39 in 2002–17.87 in 2019 (AAPC = −2.6; 95 %CI = −3.0 to −2.1), and the ASMR showed a statistically significant decreasing trend from 15.92 in 2002–11.2 in 2021 (AAPC = −1.7; 95 %CI = −2.5 to −0.9). In contrast, the ASIR for corpus uteri neoplasm significantly increased from 22.24 in 2002–30.41 in 2019 (AAPC = 2.2; 95 %CI = 1.2–3.4), and ASMR also showed a statistically significant increasing trend from 3.27 in 2002–6.42 in 2021 (AAPC = 3.8; 95 %CI = 2.3–5.3). ConclusionsThe study concludes that while the incidence and mortality rates for cervical and ovarian cancers in Wales have significantly decreased, corpus uteri neoplasm rates have increased during the study period. These findings underscore the need for continued efforts to improve early detection and treatment strategies, including national screening programs and public health initiatives, to mitigate the burden of these cancers.

Photoinduction of Ferroptosis and cGAS-STING Activation by a H2S-Responsive Iridium(III) Complex for Cancer-Specific Therapy.

Triggering ferroptosis represents a promising anticancer therapeutic strategy, but the development of a selective ferroptosis inducer for cancer-specific therapy remains a great challenge. Herein, a H2S-responsive iridium(III) complex NA-Ir has been well-designed as a ferroptosis inducer. NA-Ir could selectively light up H2S-rich cancer cells, primarily localize in mitochondria, intercalate into mitochondrial DNA (mtDNA), and induce mtDNA damage, exhibiting higher anticancer activity under light irradiation. Mechanistic studies showed that NA-Ir-mediated PDT triggered lipid peroxidation and glutathione peroxidase 4 downregulation through ROS production and GSH depletion, resulting in ferroptosis through multiple pathways. Moreover, the intense mtDNA damage can activate the cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) pathway, leading to ferritinophagy and further ferroptosis. RNA-sequencing analysis showed that NA-Ir-mediated PDT mainly affects the expression of genes related to ferroptosis, autophagy, and cancer immunity. This study demonstrates the first cancer-specific example with ferroptosis and cGAS-STING activation, which provides a new strategy for multimodal synergistic therapy.

Active surveillance for low-risk prostate cancer with high tumor burden at biopsy: lessons learned from a contemporary radical prostatectomy cohort.

To investigate whether initial tumor burden at biopsy could predict adverse features after radical prostatectomy (RP) in International Society of Urological Pathology (ISUP) 1 prostate cancer (PCa) patients. This retrospective study was conducted in six referral centers. The cohort included patients with ISUP 1 PCa at systematic and MRI-targeted biopsy. We defined a high tumor burden at biopsy if ≥ 20% of cores were positive. The endpoint of the study was adverse features at RP, defined as ≥ pT3a stage and/or N1 and/or ISUP ≥ 3. Sensitivity analyses were performed to assess associations between different thresholds on biopsy (percentage of positive cores [PPC] ≥ 25%, ≥ 33%, ≥ 50%, bilateral positivity and positive cores > 3) and adverse features. As the number of targeted biopsies sampled may influence the number of positive cores, we used a virtual biopsy model in which all targeted biopsy results were interpreted as a single targeted biopsy. A total of 312 contemporary patients were included. At final pathology, 99 patients (32%) had adverse features. In multivariate logistic regression analysis, there was no statistical association between PPC > 20% and adverse features (OR = 1.22; 95%CI:0.69-2.22, p = 0.5). In sensitivity analysis, tumor burden at biopsy was not associated with the risk of adverse features, regardless of the definition used (all p > 0.05). When we considered a unique virtual targeted biopsy, tumor burden remained not associated with adverse features (all p > 0.05). ISUP 1 PCa tumor burden at biopsy did not predict adverse features in this study, suggesting that it should not be used alone as an exclusion criterion when assessing eligibility for active surveillance.

T lymphocyte‑related immune response and immunotherapy in gastric cancer (Review).

Gastric cancer (GC) remains a global healthcare challenge because of its high incidence and poor prognosis. The efficacy of current chemotherapy regimens for advanced GC is limited. T cells, which have been implicated in the progression of GC, have a significant impact in the tumor microenvironment. With a more detailed understanding of the mechanisms underlying the cancer immunoediting process, immunotherapy may become a promising treatment option for patients with GC. Several clinical trials are currently investigating different mechanisms targeting the tumor immune response. The present review summarized T cell-involved immune responses and various immunotherapy strategies for GC.

Acyl-coenzyme a binding protein (ACBP) - a risk factor for cancer diagnosis and an inhibitor of immunosurveillance

BackgroundThe plasma concentrations of acyl coenzyme A binding protein (ACBP, also known as diazepam-binding inhibitor, DBI, or ‘endozepine’) increase with age and obesity, two parameters that are also amongst the most important risk factors for cancer.MethodsWe measured ACBP/DBI in the plasma from cancer-free individuals, high-risk patients like the carriers of TP53 or BRCA1/2 mutations, and non-syndromic healthy subjects who later developed cancer. In mice, the neutralization of ACBP/DBI was used in models of non-small cell lung cancer (NSCLC) and breast cancer development and as a combination treatment with chemoimmunotherapy (chemotherapy + PD-1 blockade) in the context of NSCLC and sarcomas. The anticancer T cell response upon ACBP/DBI neutralization was characterized by flow cytometry and single-cell RNA sequencing.ResultsCirculating levels of ACBP/DBI were higher in patients with genetic cancer predisposition (BRCA1/2 or TP53 germline mutations) than in matched controls. In non-syndromic cases, high ACBP/DBI levels were predictive of future cancer development, and especially elevated in patients who later developed lung cancer. In preclinical models, ACBP/DBI neutralization slowed down breast cancer and NSCLC development and enhanced the efficacy of chemoimmunotherapy in NSCLC and sarcoma models. When combined with chemoimmunotherapy, the neutralizing monoclonal antibody against ACBP/DBI reduced the frequency of regulatory T cells in the tumor bed, modulated the immune checkpoint profile, and increased activation markers.ConclusionThese findings suggest that ACBP/DBI acts as an endogenous immune suppressor. We conclude that elevation of ACBP/DBI constitutes a risk factor for the development of cancer and that ACBP/DBI is an actionable target for improving cancer immunosurveillance.

PD-L1 and VEGF dual blockade enhances anti-tumor effect on brain metastasis in hematogenous metastasis model

Immunotherapy improves survival outcomes in cancer patients, but there is still an unmet clinical need in the treatment of brain metastases. Here, we used a mouse model to investigate the antitumor effect of programmed death-ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF) dual blockade on metastatic brain tumors and evaluated immune responses during treatment. After establishing hematogenous brain metastasis by transplanting murine bladder carcinoma MBT2 cells stably expressing secNLuc reporter via the internal carotid artery of C3H/HeNCrl mice, we observed the formation of metastases not only in the brain parenchyma but also in the ventricles. The observed pathological areas showed that metastases in the ventricle were histologically larger than that in the brain parenchyma. Regarding the total tumor burden in the whole brain as revealed by Nluc activities, the combination of anti-PD-L1 antibody and anti-VEGF antibody showed a stronger anti-tumor effect than each single agent. Anti-PD-L1 antibody alone enhanced CD8+ T cell priming in regional lymph nodes, increased the proportion of activated CD8+ T cells in whole brain, and increased the density of CD8+ cells in the brain parenchyma. Furthermore, anti-VEGF antibody alone decreased microvessel density (MVD) in ventricular metastases, and the combination treatment increased intratumoral CD8+ cell density in the brain parenchyma and ventricular metastases. These results suggest that PD-L1 blockade enhanced cancer immunity not only in brain metastases lesions but also in the regional lymph nodes of the metastases, and that the addition of VEGF blockade increased the antitumor effect by increasing the infiltration of activated CD8+ T cell and decreasing MVD.

Analysis of urine cell-free DNA in bladder cancer diagnosis by emerging bioactive technologies and materials.

Urinary cell-free DNA (UcfDNA) is gaining recognition as an important biomarker for diagnosing bladder cancer. UcfDNA contains tumor derived DNA sequences, making it a viable candidate for non-invasive early detection, diagnosis, and surveillance of bladder cancer. The quantification and qualification of UcfDNA have demonstrated high sensitivity and specificity in the molecular characterization of bladder cancer. However, precise analysis of UcfDNA for clinical bladder cancer diagnosis remains challenging. This review summarizes the history of UcfDNA discovery, its biological properties, and the quantitative and qualitative evaluations of UcfDNA for its clinical significance and utility in bladder cancer patients, emphasizing the critical role of UcfDNA in bladder cancer diagnosis. Emerging bioactive technologies and materials currently offer promising tools for multiple UcfDNA analysis, aiming to achieve more precise and efficient capture of UcfDNA, thereby significantly enhancing diagnostic accuracy. This review also highlights breakthroughs in detection technologies and substrates with the potential to revolutionize bladder cancer diagnosis in clinic.

The value of 18F-fluorodeoxyglucose positron emission tomography-based radiomics in non-small cell lung cancer

ABSTRACT Currently, the second most commonly diagnosed cancer in the world is lung cancer, and 85% of cases are non-small cell lung cancer (NSCLC). With growing knowledge of oncogene drivers and cancer immunology, several novel therapeutics have emerged to improve the prognostic outcomes of NSCLC. However, treatment outcomes remain diverse, and an accurate tool to achieve precision medicine is an unmet need. Radiomics, a method of extracting medical imaging features, is promising for precision medicine. Among all radiomic tools, 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET)-based radiomics provides distinct information on glycolytic activity and heterogeneity. In this review, we collected relevant literature from PubMed and summarized the various applications of 18F-FDG PET-derived radiomics in improving the detection of metastasis, subtyping histopathologies, characterizing driver mutations, assessing treatment response, and evaluating survival outcomes of NSCLC. Furthermore, we reviewed the values of 18F-FDG PET-based deep learning. Finally, several challenges and caveats exist in the implementation of 18F-FDG PET-based radiomics for NSCLC. Implementing 18F-FDG PET-based radiomics in clinical practice is necessary to ensure reproducibility. Moreover, basic studies elucidating the underlying biological significance of 18F-FDG PET-based radiomics are lacking. Current inadequacies hamper immediate clinical adoption; however, radiomic studies are progressively addressing these issues. 18F-FDG PET-based radiomics remains an invaluable and indispensable aspect of precision medicine for NSCLC.

Unusual Pattern of Spread of High-Grade Serous Fallopian Tubal Carcinoma in a Woman with BRCA1 Gene Mutation

A 40-year-old woman presented with chronic watery vaginal discharge for one-month and right pelvic pain radiating to the right flank for 2 weeks. Physical and pelvic examination revealed a right pelvic mass. Computerized tomography and magnetic resonance of whole abdomen revealed a 6-cm of heterogeneous mass at the right adnexa and a larger mass of 8-cm with internal cystic portions compressing on the inferior vena cava. Her serum cancer antigen (CA) 125 elevated to 540 U/ml. Surgical intervention revealed a right fallopian tube mass with an intact serosal surface, several enlarged pelvic and para-aortic nodes, and a bulky precaval node. No gross peritoneal nor other organ invasion was found. Complete surgical staging was performed by gynecologic oncologists and a surgeon, resulting in optimal surgery. Pathology revealed high-grade serous carcinoma of the right fallopian tube with metastasis to all resected nodes and a positive peritoneal cytology. Subsequent blood testing showed BReast CAncer (BRCA) 1 gene mutation. Adjuvant therapy with paclitaxel/carboplatin/bevacizumab was given for six cycles. Maintenance therapy with bevacizumab/olaparib, and periodic surveillance for other cancers, including breast magnetic resonance imaging were planned. This case presented an unusual pattern fallopian tubal cancer spread to a large precaval lymph node which was bulkier than the primary tumor. A thorough pre-operative evaluation and a surgical team specialized in cancer surgery are crucial for successful surgical management. Appropriate adjuvant treatment and follow-up for a woman with BRCA mutation were also to be emphasized.

Novel Arf1 Inhibitors Drive Cancer Stem Cell Aging and Potentiate Anti-Tumor Immunity.

The small G protein Arf1 has been identified as playing a selective role in supporting cancer stem cells (CSCs), making it an attractive target for cancer therapy. However, the current Arf1 inhibitors have limited translational potential due to their high toxicity and low specificity. In this study, two new potent small-molecule inhibitors of Arf1, identified as DU101 and DU102, for cancer therapy are introduced. Preclinical tumor models demonstrate that these inhibitors triggered a cascade of aging in CSCs and enhance anti-tumor immunity in mouse cancer and PDX models. Through single-cell sequencing, the remodeling of the tumor immune microenvironment induced by these new Arf1 inhibitors is analyzed and an increase in tumor-associated CD8+ CD4+ double-positive T (DPT) cells is identified. These DPT cells exhibit superior features of active CD8 single-positive T cells and a higher percentage of TCF1+PD-1+, characteristic of stem-like T cells. The frequency of tumor-infiltrating stem-like DPT cells correlates with better disease-free survival (DFS) in cancer patients, indicating that these inhibitors may offer a novel cancer immunotherapy strategy by converting the cold tumor immune microenvironment into a hot one, thus expanding the potential for immunotherapy in cancer patients.