Current Cancer Treatment Research Articles

616. POST-ESOPHAGECTOMY REHABILITATION IS ASSOCIATED WITH EARLY IMPROVEMENTS IN PHYSICAL FITNESS AND SARCOPENIA: PRELIMINARY RESULTS FROM THE FITNESS AFTER OESOPHAGECTOMY (FARO) TRIAL

Abstract Introduction Curative treatment of gastro-esophageal cancer encompasses surgery and peri-operative chemo(radio)therapy. Advancements in oncological treatment and surgical techniques have resulted in incremental prognostic gains with increasing focus on survivorship and optimising quality of life (QoL). Despite enhanced recovery pathways, patients receive no assistance to improve physical functioning and QoL in the post-esophagectomy recovery period. Post-operative rehabilitation has demonstrated improvement in physical fitness and psychosocial wellbeing among other cancer subtypes. The aim of this study was to determine the impact of a patient-directed, home-based rehabilitation programme upon physical functioning in the early recovery phase following an esophagectomy. Methods The Fitness AfteR Oesophagectomy (FARO) study was a prospective, single-centre, parallel-group, open-label, two-arm, pragmatic randomised controlled external pilot trial. Patients were randomised to receive post-operative rehabilitation (alongside routine care- REHAB) or standard clinical care (NO-REHAB) alone in a 1:1 ratio. The rehabilitation intervention encompassed a 12-week home-based programme with weekly step-count targets, completion of resistance exercises and dietary monitoring. Cardiorespiratory fitness was determined by the 6-minute walk test (6MWT) and the functional impact of sarcopenia was assessed by the hand-grip strength (HGS). Outcomes were measured at baseline and 6 weeks post-esophagectomy. Between-group differences were analysed using linear mixed effects models. Results A total of 60 patients were included and randomised to REHAB (n=31) or NO-REHAB (n=29). A total of 29 patients in the REHAB group (93.5%) completed the rehabilitation programme with a 100% adherence rate. At 6 weeks post-esophagectomy, there was statistically significant improvements in the functional impact of sarcopenia as denoted by improvements in HGS in REHAB versus the NO-REHAB cohorts (mean difference= 4.237; 95% c.i 0.80-7.70; p=0.017). Cardiopulmonary fitness, as determined by the 6MWT, was comparable between cohorts with no statistically significant intergroup differences at 6 weeks (mean difference= 62.008; 95% c.i -5.85-129.91; p=0.073). Conclusion Post-operative rehabilitative interventions result in improvements in physical functioning in the early recovery phase following an esophagectomy. Further analysis from the FARO trial will determine if rehabilitation restores and improves QoL and recovery of cardiopulmonary fitness into survivorship.

784. NO SUPPORT FOR IMMEDIATE POSTOPERATIVE REMOVAL OF NASOGASTRIC TUBE AFTER ESOPHAGECTOMY, RESULTS FROM A NORDIC MULTICENTER RANDOMIZED CONTROLLED TRIAL

Abstract Background Esophagectomy is central in curative treatment of esophageal and gastroesophageal junctional cancer. Postoperative nasogastric (NG) tube for drainage of the gastric conduit is routine in most centers. The NG tube is typically associated with significant discomfort for the patients and may have risks of its own. Immediate postoperative removal of the NG tube has been suggested and deemed safe in several smaller trials. We hypothesized that immediate postoperative removal of the NG tube is non-inferior to keeping the NG-tube in place for 5 days postoperatively, with regard to anastomotic leak and other early outcomes. Methods Esophagectomy patients with a gastric conduit reconstruction were included in a multicenter, randomized controlled trial between February 2022 and March 2024. A 1:1 randomization stratified for center, age and anastomotic site (thorax/neck) was performed between immediate postoperative removal of NG tube (intervention) and 5 days of NG tube use (control). All patients underwent chest CT postoperative day 7. Anastomotic leak was the primary endpoint and a non-inferiority threshold of -9% difference in proportion of anastomotic leak, including 95% confidence interval, was set. Secondary endpoints included overall complications, pneumonia, length of stay as well as days in high dependency ward. Results Intention to treat analyses were performed on 444 patients whereof 215 were randomized to immediate NG-tube removal and 229 to control. Mean age was 67 years and neck anastomosis was performed in 78 patients (18%). 47 patients (22 %) had leak in the no NG tube group compared to 35 (15%) in the control group. Non-inferiority could not be established with a difference leak proportion to the advantage of NG tube use of 6.6% (95% CI: 13.8%-(-0.7%)). Overall complications (Clavien-Dindo >2) occurred in 94 patients (44%) in the experimental group and 91 patients (40%) in the control group. Overall 30d mortality was 1.1%. Conclusion In this randomized controlled multicenter trial, the by far largest to be performed so far, we could not establish non-inferiority for abstaining from postoperative NG tube use after esophagectomy with regards to anastomotic leak, and therefore support NG tube use. The somewhat high proportion of leak could be partly due to meticulous complication registration, including CT with peroral contrast on day seven in all patients. Use of postoperative decompression of the gastric conduit with an NG tube should be encouraged.

Tertiary lymphoid structures and their therapeutic implications in cancer.

Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates formed by the structured accumulation of immune cells such as B cells and T cells in non-lymphoid tissues induced by infection, inflammation, and tumors. They play a crucial role in the immune response, particularly in association with tumor development, where they primarily exert anti-tumor immune functions during tumorigenesis. Current research suggests that TLSs inhibit tumor growth by facilitating immune cell infiltration and are correlated with favorable prognosis in various solid tumors, serving as an indicator of immunotherapy effectiveness to some extent. Therefore, TLSs hold great promise as a valuable biomarker. Most importantly, immunotherapies aimed to prompting TLSs formation are anticipated to be potent adjuncts to current cancer treatment. This review focuses on the formation process of TLSs and their potential applications in cancer therapy.

A glycolysis-related signature to improve the current treatment and prognostic evaluation for breast cancer.

As a heterogeneous malignancy, breast cancer (BRCA) shows high incidence and mortality. Discovering novel molecular markers and developing reliable prognostic models may improve the survival of BCRA. The RNA-seq data of BRCA patients were collected from the training set The Cancer Genome Atlas (TCGA)-BRCA and validation set GSE20685 in the Gene Expression Omnibus (GEO) databases. The "GSVA" R package was used to calculate the glycolysis score for each patient, based on which all the patients were divided into different glycolysis groups. The "limma" package was employed to perform differentially expression genes (DEGs) analysis. Key signature genes were selected by performing un/multivariate and least absolute shrinkage and selection operator (LASSO) C regression and used to develop a RiskScore model. The ESTIMATE and MCP-Counter algorithms were used for quantifying immune infiltration level. The functions of the genes were validated using Western blot, colony formation, transwell and wound-healing assay. The glycolysis score and prognostic analysis showed that high glycolysis score was related to tumorigenesis pathway and a poor prognosis in BRCA as overactive glycolysis inhibited the normal functions of immune cells. Subsequently, we screened five key prognostic genes using the LASSO Cox regression analysis and used them to establish a RiskScore with a high classification efficiency. Based on the results of the RiskScore, it was found that patients in the high-risk group had significantly unfavorable immune infiltration and prognostic outcomes. A nomogram integrating the RiskScore could well predict the prognosis for BRCA patients. Knockdown of PSCA suppressed cell proliferation, invasion and migration of BRCA cells. This study developed a glycolysis-related signature with five genes to distinguish between high-risk and low-risk BRCA patients. A nomogram developed on the basis of the RiskScore was reliable to predict BRCA survival. Our model provided clinical guidance for the treatment of BRCA patients.

Abstract Mo025: Noninvasive cardiac phenotyping in patients treated with chemo- and immunotherapy for breast cancer

Current breast cancer diagnosis and treatment protocols achieve survival rates of>80% at 10 years.However, long-term cancer survivors have>4-fold higher incidence of cardiovascular complications, including heart failure.Early potentially reversible changes that may underlie downstream irreversible loss of mechanical function are unknown.Therefore, we aimed to test the feasibility of a noninvasive cardiac phenotyping protocol in patients undergoing treatment for breast cancer with doxorubicin, without or with immune checkpoint inhibitors, including multiparametric proton cardiac magnetic resonance(CMR) imaging and novel metabolic carbon13MR. A comprehensive set of studies included conventional 1HCMR,as well as metabolic 13CCMR using hyperpolarized(HP)[1-13C] pyruvate, following an oral glucose load. 13CCMR with HP[1-13C] pyruvate allows the detection of downstream metabolites of injected pyruvate within the myocardium: bicarbonate from mitochondrial oxidation and lactate from anaerobic cytosolic metabolism.HP[1-13C]pyruvate was prepared using dynamic nuclear polarization in a commercial polarizer.Imaging and spectroscopy(MRS) of hyperpolarized pyruvate was conducted using a 13C transmit/receive Helmholtz loop-pair coil on a 3Tscanner.13C data were acquired from a short-axis slice, ECG-triggered in end-systole. ProtonCMR images were analyzed using Circle, and 13CCMR images were analyzed using MATLAB. The left ventricular mid-myocardium and blood pool were segmented for metabolite quantitation. Baseline cardiac studies were performed in a consecutive series of 25 women treated for breast cancer. Of these 14(56%) were Caucasian, 3(12%) were Hispanic, 5(20%) Black, and 3(12%) Asian, with ages ranging 46±11 years.Patients received standard-of-care treatment plans based on the tumor type: 11 patients were treated with dose-dense anthracycline and cyclophosphamide, and 14 also received pembrolizumab. The comprehensive baseline phenotyping protocol is planned to be repeated after standard of care therapy in all patients. Baseline data are presented in Table1, with values reported as mean±standard deviation. Noninvasive cardiac phenotyping, including dynamic detection of metabolic substrate utilization is feasible,without showing significant adverse effects,and is well tolerated in a diverse group of patients.Completion of this protocol post-oncological therapy may allow to detect early changes in cardiac function due to chemo-and immunotherapy in susceptible patients.

Synthesis and in-silico Studies of 4-phenyl thiazol-2-amine Derivatives as Putative Anti-breast Cancer Agents.

Breast cancer (BC) is the second-leading cause of cancer-related fatalities in women after lung cancer worldwide. The development of BC is significantly influenced by estrogen receptors (ERs). The problem with current cancer treatments is selectivity, target specificity, cytotoxicity, and developing resistance. Thiazole scaffolds are gaining popularity in drug discovery due to their broad range of biological activity. It has the extraordinary capacity to control a variety of cellular pathways, and its potential for selective anticancer activity can be explored. Synthesis and in-silico</i> studies of 4-Phenyl thiazol-2-amine derivatives as anti-breast cancer agents and molecular docking was used to assess the compounds' capacity to bind ER-α protein target. In this study, 4-Phenylthiazol-2-amine derivatives (3a-j) have been synthesized, and using Schrodinger software, molecular docking and ADME studies of the compounds were conducted. Most of the synthesized compounds have shown dock scores ranging from -6.658 to - 8.911 kcal/mol, which is better than the standard drug tamoxifen (-6.821 kcal/mol). According to molecular docking, all compounds fit in the protein's active site and have the same hydrophobic pocket as the standard drug tamoxifen. Further, all of the compounds' ADME properties are below acceptable limits. Compound 3e showed the best docking score of -8.911. All compounds' ADME properties are within acceptable limits, and their p/o coefficients fall within a range, suggesting they will all have sufficient absorption at the site of action. These compounds can be evaluated invitro</i> and in-vivo</i> in the future.

Supervised, structured and individualized exercise in metastatic breast cancer: a randomized controlled trial

Physical exercise both during and after curative cancer treatment has been shown to reduce side effects. Evidence in the metastatic cancer setting is scarce, and interventions that improve health-related quality of life (HRQOL) are much needed for patients with metastatic breast cancer (MBC). The multinational randomized controlled PREFERABLE-EFFECT trial assessed the effects of exercise on fatigue and HRQOL in patients with MBC. In total, 357 patients with MBC and a life expectancy of ≥6 months but without unstable bone metastases were recruited at eight study centers across five European countries and Australia. Participants were randomly assigned (1:1) to usual care (control group, n = 179) or a 9-month supervised exercise program (exercise group, n = 178). Intervention effects on physical fatigue (European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-FA12 scale) and HRQOL (EORTC QLQ-C30 summary score) were determined by comparing the change from baseline to 3, 6 (primary timepoint) and 9 months between groups using mixed models for repeated measures, adjusted for baseline values of the outcome, line of treatment (first or second versus third or higher) and study center. Exercise resulted in significant positive effects on both primary outcomes. Physical fatigue was significantly lower (−5.3 (95% confidence interval (CI), −10.0 to −0.6), Bonferroni–Holm-adjusted P = 0.027; Cohen's effect size, 0.22) and HRQOL significantly higher (4.8 (95% CI, 2.2–7.4), Bonferroni–Holm-adjusted P = 0.0003; effect size, 0.33) in the exercise group than in the control group at 6 months. Two serious adverse events occurred (that is, fractures), but both were not related to bone metastases. These results demonstrate that supervised exercise has positive effects on physical fatigue and HRQOL in patients with MBC and should be recommended as part of supportive care.ClinicalTrials.gov Identifier: NCT04120298.

Perioperative outcomes in patients who undergo neoadjuvant chemoradiotherapy versus chemotherapy versus up-front surgery in patients with oesophageal cancer.

Oesophagectomy is the mainstay of curative treatment for oesophageal cancer. The role of neoadjuvant therapy has evolved over time as evidence for its survival benefit comes to hand. Clinician reluctance to offer patients neoadjuvant therapy may be based on the perception that patients receiving treatment before surgery may be exposed to a greater risk of perioperative complications. The aim of this study was to examine short-term outcomes in patients who undergo neoadjuvant therapy versus up-front surgery in patients with oesophageal cancer. This was a retrospective cohort study of prospectively collated data from 2001 to 2020 of patients undergoing resection for oesophageal cancer. Patients who had neoadjuvant chemoradiotherapy, chemotherapy and up-front surgery were compared for perioperative morbidity (via the Clavien-Dindo classification), length of stay, unplanned readmission, and 30- and 90-day mortality. Logistic regression was performed to predict perioperative morbidity following surgery. In total, 284 patients underwent an oesophagectomy. Most patients received neoadjuvant treatment (41% received chemoradiotherapy (117/284), 33% received chemotherapy (93/284)), and 26% of patients received up-front surgery (74/284). Patients who received neoadjuvant chemoradiotherapy or up-front surgery were more likely to have a complication (57%, 67/117 and 57%, 43/74) than patients who received neoadjuvant chemotherapy only (38%, 35/93, P = 0.009). The 30- and 90-day mortality rates were 1.4% (n = 4) and 2.8% (n = 8), respectively, with no difference between the use of neoadjuvant therapy. In this series, we found that patients who received neoadjuvant treatment could undergo oesophagectomy with curative intent with acceptable postoperative morbidity and mortality.

An mRNA vaccine for pancreatic cancer designed by applying in silico immunoinformatics and reverse vaccinology approaches.

Pancreatic ductal adenocarcinoma is the most prevalent pancreatic cancer, which is considered a significant global health concern. Chemotherapy and surgery are the mainstays of current pancreatic cancer treatments; however, a few cases are suitable for surgery, and most of the cases will experience recurrent episodes. Compared to DNA or peptide vaccines, mRNA vaccines for pancreatic cancer have more promise because of their delivery, enhanced immune responses, and lower proneness to mutation. We constructed an mRNA vaccine by analyzing S100 family proteins, which are all major activators of receptors for advanced glycation end products. We applied immunoinformatic approaches, including physicochemical properties analysis, structural prediction and validation, molecular docking study, in silico cloning, and immune simulations. The designed mRNA vaccine was estimated to have a molecular weight of 165023.50 Da and was highly soluble (grand average of hydropathicity of -0.440). In the structural assessment, the vaccine seemed to be a well-stable and functioning protein (Z score of -8.94). Also, the docking analysis suggested that the vaccine had a high affinity for TLR-2 and TLR-4 receptors. Additionally, the molecular mechanics with generalized Born and surface area solvation analysis of the "Vaccine-TLR-2" (-141.07 kcal/mol) and "Vaccine-TLR-4" (-271.72 kcal/mol) complexes also suggests a strong binding affinity for the receptors. Codon optimization also provided a high expression level with a GC content of 47.04% and a codon adaptation index score 1.0. The appearance of memory B-cells and T-cells was also observed over a while, with an increased level of helper T-cells and immunoglobulins (IgM and IgG). Moreover, the minimum free energy of the mRNA vaccine was predicted at -1760.00 kcal/mol, indicating the stability of the vaccine following its entry, transcription, and expression. This hypothetical vaccine offers a groundbreaking tool for future research and therapeutic development of pancreatic cancer.

Predicting the Population Health Economic Impact of Current and New Cancer Treatments for Colorectal Cancer: A Data-Driven Whole Disease Simulation Model for Predicting the Number of Patients with Colorectal Cancer by Stage and Treatment Line in Australia

ObjectivesEffective healthcare planning, resource allocation, and budgeting require accurate predictions of the number of patients needing treatment at specific cancer stages and treatment lines. The Predicting the Population Health Economic Impact of Current and New Cancer Treatments (PRIMCAT) for Colorectal Cancer (CRC) simulation model (PRIMCAT-CRC) was developed to meet this requirement for all CRC stages and relevant molecular profiles in Australia. MethodsReal-world data were used to estimate treatment utilization and time-to-event distributions. This populated a discrete-event simulation, projecting the number of patients receiving treatment across all disease stages and treatment lines for CRC and forecasting the number of patients likely to utilize future treatments. Illustrative analyses were undertaken, estimating treatments across disease stages and treatment lines over a 5-year period (2022-2026). We demonstrated the model’s applicability through a case study introducing pembrolizumab as a first-line treatment for mismatch-repair-deficient stage IV. ResultsClinical registry data from 7163 patients informed the model. The model forecasts 15 738 incident and 2821 prevalent cases requiring treatment in 2022, rising to 15 921 and 2871, respectively, by 2026. Projections show that over 2022 to 2026, there will be a total of 116 752 treatments initiated, with 43% intended for stage IV disease. The introduction of pembrolizumab is projected for 706 patients annually, totaling 3530 individuals starting treatment with pembrolizumab over the forecasted period, without significantly altering downstream utilization of subsequent treatments. ConclusionsPRIMCAT-CRC is a versatile tool that can be used to estimate the eligible patient populations for novel cancer therapies, thereby reducing uncertainty for policymakers in decisions to publicly reimburse new treatments.

A novel nanodrug for the sensitization of photothermal chemotherapy for breast cancer in vitro.

Owing to the complexity of tumor treatment, clinical tumor treatment has evolved from a single treatment mode to multiple combined treatment modes. Reducing the tolerance of tumors to heat and the toxicity of chemotherapy drugs to the body, as well as increasing the sensitivity of tumors to photothermal therapy and chemotherapy drugs, are key issues that urgently need to be addressed in the current cancer treatment. In this work, polylactic acid-based drug nanoparticles (PLA@DOX/GA/ICG) were synthesized with good photothermal conversion ability by encapsulating the water-soluble anticancer drug doxorubicin (DOX), photothermal conversion agent indocyanine green (ICG) and liposoluble drug gambogic acid (GA) using a double emulsion method. The preparation process of PLA@DOX/GA/ICG was examined. Gambogic acid entrapped in PLA@DOX/GA/ICG nanoparticles could act as an HSP90 protein inhibitor to achieve bidirectional sensitization to chemotherapy and photothermal therapy under 808 nm laser irradiation for the first time, effectively ablating breast cancer cells in vitro. This nanodrug was expected to be used for the efficient treatment of tumors.

Disease-specific health-related quality of life trajectories up to 15 years after curative treatment for esophageal cancer-a prospective cohort study.

The presence of distinct long-term disease-specific HRQL trajectories after curative treatment for esophageal cancer and factors associated with such trajectories are unclear. This population-based and longitudinal cohort study included 425 esophageal cancer patients who underwent curative treatment, including esophagectomy, in Sweden in 2001-2005 and were followed up until 2020, that is, 15-year follow-up. The outcomes were 10 disease-specific HRQL symptoms, measured by the well-validated EORTC QLQ-OES18 questionnaire at 6 months (n = 402 patients), and 3 (n = 178), 5 (n = 141), 10 (n = 92), and 15 years (n = 52) after treatment. HRQL symptoms were examined for distinct trajectories by growth mixture models. Weighted logistic regression models provided odds ratios (OR) with 95% confidence intervals (95% CI) for nine factors in relation to HRQL trajectories: age, sex, education, proxy baseline HRQL, comorbidity, tumor histology, chemo(radio)therapy, pathological tumor stage, and postoperative complications. Distinct HRQL trajectories were identified for each of the 10 disease-specific symptoms. HRQL trajectories with more symptoms tended to persist or alleviate over time, while trajectories with fewer symptoms were more stable. Eating difficulty had three trajectories: persistently less, persistently moderate, and persistently more symptoms. The OR of having a persistently more eating difficulty trajectory was decreased for adenocarcinoma histology (OR = 0.44, 95% CI 0.21-0.95), and increased for pathological tumor stage III-IV (OR = 2.19, 95% CI 0.99-4.82) and 30-day postoperative complications (OR = 2.54, 95% CI 1.26-5.12). Distinct trajectories with long-term persistent or deteriorating disease-specific HRQL symptoms were identified after esophageal cancer treatment. Tumor histology, tumor stage, and postoperative complications may facilitate detection of high-risk patients for unwanted trajectories.

Synthesis, biological screening, and binding mode analysis of some N-substituted tetrahydroquinoline analogs as apoptosis inducers and anticancer agents

One of the most common malignancies in the world is lung cancer. Lung cancer involves mutations in many different genes, however, EGFR, KRAS, PTEN, and PIK3CA involvement is more frequent. The lack of effective drugs and drug resistance are major issues and obstacles associated with the current treatment of lung cancer. Seven novel tetrahydroquinoline analogs were synthesized and screened against a range of cancer cell lines in this study. Among these, 17f (IC50=0.082 µM) was shown to be the most potent when compared to the standard drug 5-Flurouracil (5FU) (IC50=0.28 µM). Moreover, flow cytometry analysis was carried out to ascertain the nature of programmed cell death. This provides conclusive evidence of late apoptosis in all synthesized compounds when contrasted with the standard drug (5FU) and control. After comparing all of the outputs, additional binding mode analysis was carried out to determine the potential mechanism of its anticancer activity. Molecular docking and MD simulation studies were carried out, and the results show that all of the synthesized compounds 17-a-f (17f docking score -10.5 Kcal/mol) have a better binding affinity towards mTOR (PDB id: 4JT6) than both the standard drug 5FU and the co-crystal ligand X6K (docking score: -7.6 Kcal/mol). Despite the aforementioned information, strong hit compounds from this series may eventually be developed to become lead mTOR inhibitors for the treatment of lung cancer.

CT-Guided Percutaneous Cryoablation of Breast Cancer: A Single-Center Experience.

This study shall retrospectively evaluate the efficacy and safety of liquid-nitrogen based CT-guided cryoablation (CA) as a minimal-invasive technique for the curative treatment of primary breast cancer. A total of 45 female patients with 56 tumors were treated by CT-guided CA in analgosedation as an outpatient procedure. We used a liquid-nitrogen based system with a single cryoprobe and performed two freeze cycles with an intermediate thawing. The mean tumor diameter was 1.6 ± 0.7 cm. Follow-up was conducted via contrast-enhanced MR images of the breast. No complications were observed in all 56 ablations. Initial complete ablation was achieved in 100% of cases. Four cases of local tumor progression were reported, resulting in a rate of 8.9%, and 6 cases of intramammary distant recurrence at a rate of 13.3%. The extramammary tumor progression was observed in 7 patients at a rate of 15.6%. The mean overall survival was 4.13 years (95% CI: 3.7-4.5). The mean overall progression-free survival was 2.5 years (95% CI: 1.8-3.2) and the mean local progression-free survival was 2.9 years (95% CI: 2.3-3.6). Cryoablation is a safe and effective treatment for primary breast cancer tumors, which can be performed in analgosedation and as an outpatient procedure. However, potential for improvement exists and further evidence is necessary.

The preclinical discovery and development of zolbetuximab for the treatment of gastric cancer

ABSTRACT Introduction Gastric cancer remains a formidable challenge in oncology with high mortality rates and few advancements in treatment. Claudin-18.2 (CLDN18.2) is a tight junction protein primarily expressed in the stomach and is frequently overexpressed in certain subsets of gastric cancers. Targeting CLDN18.2 with monoclonal antibodies, such as zolbetuximab (IMAB362), has shown promising efficacy results in combination with chemotherapy. Areas covered The molecular cell biology of CLDN18.2 is discussed along with studies demonstrating the utility of CLDN18.2 expression as a biomarker and therapeutic target. Important clinical studies are reviewed, including Phase III trials, SPOTLIGHT and GLOW, which demonstrate the efficacy of zolbetuximab in combination with chemotherapy in patients with CLDN18.2-positive advanced gastric cancer. Expert opinion CLDN18.2 is involved in gastric differentiation through maintenance of epithelial barrier function and coordination of signaling pathways, and its expression in gastric cancers reflects a ‘gastric differentiation’ program. Targeting Claudin-18.2 represents the first gastric cancer specific ‘targeted’ treatment. Further studies are needed to determine its role within current gastric cancer treatment sequencing, including HER2-targeted therapies and immunotherapies. Management strategies will also be needed to better mitigate zolbetuximab-related treatment side effects, including gastrointestinal (GI) toxicities.

Combined Pubic Arch and Ischial Bone Resection for Metachronous and Frequent Local Recurrences of Rectal Cancer.

Complete surgical resection with negative margins remains the cornerstone for curative treatment of rectal cancer; however, local recurrence can pose a significant challenge. Herein, we aimed to introduce a novel surgical technique for combined resection of the pubic arch and ischial bone in the context of treating recurrent rectal cancer. We present a case of a patient with a fourth local recurrence of rectal cancer, with no evidence of distant metastasis. The tumor directly invaded the posterior wall of the pubic arch. To achieve complete tumor resection, an osteotomy was performed using a thread wire saw at the bilateral pubic rami and ischial bones. Intraoperative frozen section analysis (rapid tissue examination) was conducted on tissue samples from the lateral margins of the planned osteotomy line. Samples were negative for adenocarcinoma (cancerous cells). The combined resection of the pubic arch and ischial bone was successfully performed with negative margins for adenocarcinoma, as confirmed by frozen section analysis. Mastery of the surgical technique for combined resection of the pubic arch and ischial bone may be clinically significant for achieving complete resection in cases of multiple resections for locally recurrent rectal cancer.

Shared genetics between breast cancer and predisposing diseases identifies novel breast cancer treatment candidates.

Current effective breast cancer treatment options have severe side effects, highlighting a need for new therapies. Drug repurposing can accelerate improvements to care, as FDA-approved drugs have known safety and pharmacological profiles. Some drugs for other conditions, such as metformin, an antidiabetic, have been tested in clinical trials for repurposing for breast cancer. Here, we exploit the genetics of breast cancer and linked predisposing diseases to propose novel drug repurposing. We hypothesize that if a predisposing disease contributes to breast cancer pathology, identifying the pleiotropic genes related to the risk of cancer could prioritize drug targets, among all drugs treating a predisposing disease. We aim to develop a method to not only prioritize drug repurposing, but also to highlight shared etiology explaining repurposing. We compile breast cancer's predisposing diseases from literature. For each predisposing disease, we use GWAS summary statistics to identify genes in loci showing genetic correlation with breast cancer. Then, we use a network approach to link these shared genes to canonical pathways, and similarly for all drugs treating the predisposing disease, we link their targets to pathways. In this manner, we are able to prioritize a list of drugs based on each predisposing disease, with each drug linked to a set of implicating pathways. Finally, we evaluate our recommendations against drugs currently under investigation for breast cancer. We identify 84 loci harboring mutations with positively correlated effects between breast cancer and its predisposing diseases; these contain 194 identified shared genes. Out of the 112 drugs indicated for the predisposing diseases, 76 drugs can be linked to shared genes via pathways (candidate drugs for repurposing). Fifteen out of these candidate drugs are already in advanced clinical trial phases or approved for breast cancer (OR = 9.28, p = 7.99e-03, one-sided Fisher's exact test), highlighting the ability of our approach to identify likely successful candidate drugs for repurposing. Our novel approach accelerates drug repurposing for breast cancer by leveraging shared genetics with its known risk factors. The result provides 59 novel candidate drugs alongside biological insights supporting each recommendation.

Lectins as a promising therapeutic agent for breast cancer: A review.

Efficient treatment of cancer has been a subject of research by scientists for many years. Current treatments for cancer, such as radiotherapy, chemotherapy and surgery have been used in traditional combination therapy, but they have major setbacks like non-specificity, non-responsiveness in certain cancer types towards treatment, tumor recurrence, etc. Epidemiological data has shown that breast cancer accounts for 14% of cancer cases occurring in Indian women. In recent years, scientists have started to focus on the use of natural compounds like lectins obtained from various sources to counter the side effects of traditional therapy. Lectins like Sambucus nigra Agglutinin, Maackia amurensis lectin, Okra lectins, Haliclona caerulea lectin, Sclerotium rolfsii lectin, etc., have been discovered to have both diagnostic and therapeutic potential for breast cancer patients. Lectins have been found to have inhibitory effects on various cancer cell activities such as neo-angiogenesis, causing cell cycle arrest at the G1 phase, and inducing apoptosis. The major idea behind the use of lectins in cancer diagnostics and therapeutics is their capability to bind to glycosylated proteins that are expressed on the cell surface. This review focuses on an exploration of the roles of post-translational modification in cancer cells, especially glycosylation, and the potential of lectins in cancer diagnosis and therapeutics.

Laparoscopic Indocyanine Green-Guided Sentinel Lymph Node Biopsy for Gallbladder Neoplasms.

Surgical resection, the only potentially curative treatment for gallbladder cancer (GBC), entails an extended cholecystectomy with portal lymphadenectomy. Lymph node dissection is a key staging procedure, but its therapeutic value is unclear. Additionally, it is technically challenging and potentially harmful. Methods for better assessment of lymph node status are needed. This report presents a case of indocyanine green (ICG)-guided sentinel lymph node biopsy (SNLB) for a patient with a gallbladder mass suspicious for GBC. An 81-year-old woman consulted for abdominal discomfort. Abdominal ultrasound showed an intraluminal gallbladder mass suspicious for GBC. Staging imaging did not show liver invasion, lymphadenopathy, or distant metastasis. Given the woman's advanced age and limited extent of disease, a laparoscopic extended cholecystectomy with an ICG-guided SLNB was performed. Injection of 1 ml of ICG (0.125 mg/mL) into the gallbladder bed was performed using a 22-gauge needle, avoiding direct injection into the gallbladder wall. A near-infrared camera was used to visualize real-time ICG flow through the lymphatic vessels of the gallbladder toward the cystic node. Then, a sentinel lymph node posterolateral to the bile duct (station 12b) was identified. The node was resected and sent for permanent section. The procedure continued with an extended cholecystectomy. Pathology showed an intracholecystic papillary neoplasm with high-grade dysplasia. Cystic and sentinel lymph nodes were negative for malignancy. For patients with gallbladder neoplasms, ICG-guided SLNB is a feasible technique that could allow for treatment de-escalation. Further evaluation in clinical trials is needed.

Optimizing Liposomal Drug Delivery for Enhanced Efficacy in Skin Cancer Treatment: A Comprehensive Experimental Investigation

Skin cancer is a prevalent global health issue, necessitating ongoing research into innovative treatment approaches. This study focuses on assessing the effectiveness of a liposomal formulation to enhance skin cancer treatment and demonstrates its technological viability. A comprehensive literature review establishes the context by examining current skin cancer treatments and the role of liposomal formulations in dermatological therapies. The research objectives are clearly outlined, detailing the liposomal formulation's characteristics and experimental methodologies. Results from the study, including comparisons with existing treatments and statistical analyses, are presented, offering insights into the formulation's potential for advancing skin cancer therapy. The discussion section interprets the findings, addresses limitations, and underscores the transformative impact of liposomal formulations in skin cancer treatment. The conclusion succinctly summarizes key findings, emphasizing the study's significance. Furthermore, the future directions section outlines potential research avenues and improvements to the liposomal formulation. This research contributes to the evolving landscape of skin cancer treatment, highlighting the promising role of liposomal formulations in enhancing therapeutic outcomes. By bridging the gap between scientific innovation and clinical application, this study provides valuable insights into the potential of liposomal formulations to revolutionize skin cancer treatment, ultimately contributing to improved patient outcomes and a more effective approach to combating this widespread and pressing health concern. Keywords: Liposomal formulation, Skin cancer treatment, Technological viability, Comparative analysis, Transformative impact, Methodologies