Treatment Outcomes In Cancer Patients Research Articles

Precision Phenotypic Profiling and Capture of Circulating Tumor Cells via a Vertical Laminar Flow-Stacked Microfluidic Chip.

The heterogeneity of circulating tumor cells has a significant impact on the diagnosis, treatment, and monitoring of cancer. Research on the subtypes of circulating tumor cells can bring better treatment outcomes for cancer patients. Here, we proposed a microfluidic chip for the magnetic capture of subtypes of circulating tumor cells from the whole blood and phenotypic profiling by stacking laminar flow vertically. Circulating tumor cells were sorted and captured by the three-dimensional regulation of both magnetic fields in the vertical direction and flow fields in the lateral direction. Using EpCAM-magnetic beads, we achieved sorting and sectional capture of target cells in whole blood and analyzed the surface expression levels of the captured cells, confirming the functionality of the microfluidic chip in sorting and capturing subtypes of circulating tumor cells. This microfluidic chip can also aid in the subsequent subtype analysis of other rare cells.

Role of mitochondria in doxorubicin-mediated cardiotoxicity: From molecular mechanisms to therapeutic strategies.

This comprehensive review delves into the pivotal role of mitochondria in doxorubicin-induced cardiotoxicity, a significant complication limiting the clinical use of this potent anthracycline chemotherapeutic agent. Doxorubicin, while effective against various malignancies, is associated with dose-dependent cardiotoxicity, potentially leading to irreversible cardiac damage. The review meticulously dissects the molecular mechanisms underpinning this cardiotoxicity, particularly focusing on mitochondrial dysfunction, a central player in this adverse effect. Central to the discussion is the concept of mitochondrial quality control, including mitochondrial dynamics (fusion/fission balance) and mitophagy. The review presents evidence linking aberrations in these processes to cardiotoxicity in doxorubicin-treated patients. It elucidates how doxorubicin disrupts mitochondrial dynamics, leading to an imbalance between mitochondrial fission and fusion, and impairs mitophagy, culminating in the accumulation of dysfunctional mitochondria and subsequent cardiac cell damage. Furthermore, the review explores emerging therapeutic strategies targeting mitochondrial dysfunction. It highlights the potential of modulating mitochondrial dynamics and enhancing mitophagy to mitigate doxorubicin-induced cardiac damage. These strategies include pharmacological interventions with mitochondrial fission inhibitors, fusion promoters, and agents that modulate mitophagy. The review underscores the promising results from preclinical studies while advocating for more extensive clinical trials to validate these approaches in human patients. In conclusion, this review offers valuable insights into the intricate relationship between mitochondrial dysfunction and doxorubicin-mediated cardiotoxicity. It underscores the need for continued research into targeted mitochondrial therapies as a means to improve the cardiac safety profile of doxorubicin, thereby enhancing the overall treatment outcomes for cancer patients.

Abstract 2312: Integrating spatial multi-omics data with spatial quantitative pharmacology (spQSP) model to simulate human neoadjuvant immunotherapy clinical trial of hepatocellular carcinoma

Abstract Human clinical trials provided tremendous insights to advance novel systemic therapies and to improve treatment outcomes for cancer patients. The few durable treatment options have led to a critical need to advance new therapeutics in hepatocellular carcinoma (HCC). Recent human clinical trials have demonstrated that new combination of immunotherapeutic regimens provide augmented clinical response in a subset of patients. Computational methods that can simulate tumors from mathematical equations describing cellular and molecular interactions are emerging as promising tools to simulate the impact of therapies entirely in silico. To facilitate designing dosing regimens and selecting potential predictive biomarkers, we developed a new computational model to track tumor progression at organ scale while reflecting the spatial heterogeneity in the tumor at cellular and molecular scale in HCC. This computational model is called a spatial quantitative systems pharmacology (spQSP) platform and it is also designed to simulate the effects of combination immunotherapy. The model is first calibrated using clinical outcomes and measured immune cell densities based on recent neoadjuvant HCC clinical trial combining anti-PD-1 immunotherapy and a multitargeted tyrosine kinase inhibitor (TKI) cabozantinib (NCT03299946). Then, we validate the results from the spQSP model by leveraging real-world spatial multi-omics data from the same clinical trial. The model output is compared with spatial data from Imaging Mass Cytometry (IMC). Both IMC data and simulation results suggest closer proximity between CD8 T cell and Arginase 1 (Arg1) positive macrophages among non-responders while the reverse trend was observed for responders. We also compared the model output with Visium spatial transcriptomics analyses of samples from post-treatment tumor resections in the original clinical trial. Both spatial transcriptomic data and simulation results identify the role of spatial patterns of tumor vasculature and TGFβ in tumor and immune cell interactions. To our knowledge, this is the first spatial tumor model for virtual clinical trials at a molecular and cellular scale that is grounded in high-throughput spatial multi-omics data from a human clinical trial. Citation Format: Shuming Zhang, Atul Deshpande, Babita K. Verma, Hanwen Wang, Haoyang Mi, Long Yuan, Won Jin Ho, Elizabeth M. Jaffee, Qingfeng Zhu, Robert A. Anders, Mark Yarchoan, Luciane T. Kagohara, Elana J. Fertig, Aleksander S. Popel. Integrating spatial multi-omics data with spatial quantitative pharmacology (spQSP) model to simulate human neoadjuvant immunotherapy clinical trial of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2312.

Effects of Curcumin on Treatment Outcome in Patients with Cancer Diagnosis

Introduction: Treatment options for palliative care in patients with cancer aim to improve quality of life, and, in this context, alternative, complementary treatments are under study to reduce treatment side effects and increase traditional treatment efficacy. Curcumin is a food supplement derived from the plant Curcuma longa, which has recently received increasing attention because of its antioxidant and anti-inflammatory effects. Previous clinical trials, with different results, investigated Curcumin’s efficacy in cancer treatment. We aimed to explore the effect of Curcumin on treatment outcomes in patients with cancer diagnosis. Methods: In this systematic mini-review, conducted to answer the research question "What is the effect of curcumin on treatment outcome of cancer patients?" we searched four portals/databases (Pubmed/Medline, BVS/Lilacs, Scielo, and Cochrane). The PICOT strategy adopted was: P - patients with cancer; I - Curcumin; C- not applicable; O - treatment outcome; T- RCT and cohort studies. Independent reviewers checked for eligibility and study quality. Results: We included six studies regarding prostate cancer, head and neck tumors, colorectal cancer, breast cancer, and bladder cancer. Studies showed good tolerability for Curcumin with mild adverse effects. However, it showed no significant difference in survival or tumor progression. On the contrary, researchers observed exciting findings concerning preventing and relieving chemotherapy-related adverse effects. Discussion: Curcumin appears to be an intriguing potential adjuvant therapy in patients with cancer. Further studies on the topic are needed to investigate its possible concrete applications and to address the known problem of its poor bioavailability.

Preparation and in vitro evaluation of BBG-250 loaded liposomal formulation for anticancer potential

BackgroundLiposome-mediated drug delivery systems have emerged as a promising avenue for enhancing cancer treatment strategies. This study aims to develop and assess liposomal carriers loaded with Brilliant Blue G-250 (BBG-250), a potent P2X7 receptor antagonist that shows potential as an anti-tumor agent. Specifically, two types of liposomal formulations were designed: conventional liposomes composed of hydrogenated soya phosphatidylcholine (HSPC) and cholesterol, and pH-sensitive liposomes consisting of dioleoylphosphatidylethanolamine (DOPE), distearoylphosphatidylethanolamine-methoxy polyethylene glycol (DSPE-mPEG), dipalmitoylphosphatidylcholine (DPPC), and cholesterol. The investigation focuses on understanding the morphological characteristics, size, stability, drug incorporation efficiency, drug release profiles, blood compatibility, and cytotoxicity of these liposomal formulations.ResultsAdvanced photon correlation spectroscopy using the Nano Plus-3 instrument was employed to evaluate the liposomes. The optimized conventional liposomes (HSPC-cholesterol ratio 7:3) exhibited a size of 125 ± 0.3 nm with a polydispersity index (PDI) of 0.21, indicating uniformity. The pH-sensitive liposomes (DOPE:DPPC:DSPE-PEG2000: Cholesterol 4:3:3:0.3) demonstrated a size of 118 ± 1.2 nm with a PDI of 0.230. Zeta potential measurements confirmed the stability of both formulations under physiological conditions, with values of − 16.93 mV for conventional liposomes and − 25.21 mV for pH-sensitive liposomes. Higher drug-to-lipid ratios were found to enhance drug incorporation efficiency. pH-sensitive liposomes exhibited superior drug release characteristics, with 95% release over 24 h, compared to conventional liposomes, which released 70% of the drug. Blood compatibility assessments revealed the safety of both formulations for intravenous administration. Cytotoxicity studies conducted on A549 cell lines demonstrated the cytocompatibility of both liposomal types across a range of concentrations, with IC50 values surpassing those of the reference drug, docetaxel.ConclusionsThis study underscores the potential of liposomal carriers as effective vehicles for delivering BBG-250, highlighting their stability, biocompatibility, and controlled drug release properties. Despite being slightly less potent than the reference drug, docetaxel, these liposomal formulations hold promise for advancing anticancer strategies. The findings contribute to the evolving landscape of innovative cancer therapy drug delivery systems, offering a novel approach to improving treatment outcomes for cancer patients. The successful development and evaluation of these liposomal carriers pave the way for further investigations and potential clinical applications in the field of cancer therapeutics.

Characterization of an Injectable Chitosan Hydrogel for the Tunable, Localized Delivery of Immunotherapeutics.

Localized delivery of immunotherapeutics within a tumor has the potential to reduce systemic toxicities and improve treatment outcomes in cancer patients. Unfortunately, local retention of therapeutics following intratumoral injection is problematic and is insufficiently considered. Dense tumor architectures and high interstitial pressures rapidly exclude injections of saline and other low-viscosity solutions. Hydrogel-based delivery systems, on the other hand, can resist shear forces that cause tumor leakage and thus stand to improve the local retention of coformulated therapeutics. The goal of the present work was to construct a novel, injectable hydrogel that could be tuned for localized immunotherapy delivery. A chitosan-based hydrogel, called XCSgel, was developed and subsequently characterized. Nuclear magnetic resonance studies were performed to describe the chemical properties of the new entity, while cryo-scanning electron microscopy allowed for visualization of the hydrogel's cross-linked network. Rheology experiments demonstrated that XCSgel was shear-thinning and self-healing. Biocompatibility studies, both in vitro and in vivo, showed that XCSgel was nontoxic and induced transient mild-to-moderate inflammation. Release studies revealed that coformulated immunotherapeutics were released over days to weeks in a charge-dependent manner. Overall, XCSgel displayed several clinically important features, including injectability, biocompatibility, and imageability. Furthermore, the properties of XCSgel could also be controlled to tune the release of coformulated immunotherapeutics.

Role of mitochondria in doxorubicin-mediated cardiotoxicity: from molecular mechanisms to therapeutic strategies.

This comprehensive review delves into the pivotal role of mitochondria in doxorubicin-induced cardiotoxicity, a significant complication limiting the clinical use of this potent anthracycline chemotherapeutic agent. Doxorubicin, while effective against various malignancies, is associated with dose-dependent cardiotoxicity, potentially leading to irreversible cardiac damage. The review meticulously dissects the molecular mechanisms underpinning this cardiotoxicity, particularly focusing on mitochondrial dysfunction, a central player in this adverse effect. Central to the discussion is the concept of mitochondrial quality control (MQC), including mitochondrial dynamics (fusion/fission balance) and mitophagy. The review presents evidence linking aberrations in these processes to cardiotoxicity in doxorubicin-treated patients. It elucidates how doxorubicin disrupts mitochondrial dynamics, leading to an imbalance between mitochondrial fission and fusion, and impairs mitophagy, culminating in the accumulation of dysfunctional mitochondria and subsequent cardiac cell damage. Furthermore, the review explores emerging therapeutic strategies targeting mitochondrial dysfunction. It highlights the potential of modulating mitochondrial dynamics and enhancing mitophagy to mitigate doxorubicin-induced cardiac damage. These strategies include pharmacological interventions with mitochondrial fission inhibitors, fusion promoters, and agents that modulate mitophagy. The review underscores the promising results from preclinical studies while advocating for more extensive clinical trials to validate these approaches in human patients. In conclusion, this review offers valuable insights into the intricate relationship between mitochondrial dysfunction and doxorubicin-mediated cardiotoxicity. It underscores the need for continued research into targeted mitochondrial therapies as a means to improve the cardiac safety profile of doxorubicin, thereby enhancing the overall treatment outcomes for cancer patients.

Cannabinoids and the endocannabinoid system in immunotherapy: helpful or harmful?

Numerous studies in various cancer models have demonstrated that ingredients of cannabis can influence tumor growth through the endocannabinoid system (ECS), a network of molecules (mediators, receptors, transporters, enzymes) that maintains homeostasis and protection in many tissues. The main constituents of the ECS are the classical cannabinoid (CB) receptors, such as CB1 and CB2, their endogenous ligands (endocannabinoids), and the endocannabinoids’ synthesizing and degrading enzymes. The role of the ECS in cancer is still unclear and its effects often depend on the tumor entity and the expression levels of CB receptors. Many studies have highlighted the tumor cell-killing potential of CB1 agonists. However, cannabis is also known as an immunosuppressant and some data suggest that the use of cannabis during immunotherapy worsens treatment outcomes in cancer patients. CB receptors are widely present in immune cells, and together with monoacylglycerol lipase, the 2-arachidonoylglycerol degrading enzyme, they could be critically involved in the regulation of the immune cell profile of the tumor microenvironment (TME), and hence in tumor progression. So far, data on the impact of the ECS in the immune-TME are still vague. In this review, we discuss the current understanding of the ECS on immunoregulation during tumor growth, and how it might affect the outcome of cancer immunotherapy.

Rehabilitation Exercises Supported by Monitor-Augmented Reality for Patients with High-Grade Glioma Undergoing Radiotherapy: Results of a Randomized Clinical Trial.

Exercise has been shown to improve quality of life (QoL) and even treatment outcomes in cancer patients. However, the evidence to support the benefits of exercise in patients with high-grade glioma (HGG) is limited. Therefore, we performed a randomized clinical trial (RCT) to examine the effect of augmented-reality-based rehabilitation exercises on physical and functional fitness, cognitive function, fatigue, mood, QoL, selected blood parameters, brain derived neurotrophic factor (BDNF), and S100 protein in patients with HGG. Adult patients with HGG scheduled to undergo radiotherapy after tumor resection were randomized to participate in an exercise program (experimental group, n = 25) or to receive usual care (controls, n = 22). Physical and mental fitness was measured at baseline, after the completion of radiotherapy, and at 3 months. The following tests were administered: Handgrip Strength Test; 6-Minute Walk Test; Time Up and Go test; Functional Independent Measure scale; Addenbrooke's Cognitive Examination III (ACE III); Hospital Anxiety and Depression Scale; Functional Cancer Therapy Assessment-Brain; and Functional Assessment of Chronic Illness Therapy-Fatigue. We also measured blood parameters, BDNF, and S100 protein levels. No significant changes were observed in the exercise group. However, the controls experienced a significant decrease in HGS and in the ACE III attention domain. No significant changes were observed in QoL, fatigue, BDNF, or S100 levels in either group. Augmented-reality-based exercise during radiation therapy may prevent loss of muscle strength and attention in patients with HGG.

Notch receptor/ligand diversity: contribution to colorectal cancer stem cell heterogeneity.

Cancer cell heterogeneity is a key contributor to therapeutic failure and post-treatment recurrence. Targeting cell subpopulations responsible for chemoresistance and recurrence seems to be an attractive approach to improve treatment outcome in cancer patients. However, this remains challenging due to the complexity and incomplete characterization of tumor cell subpopulations. The heterogeneity of cells exhibiting stemness-related features, such as self-renewal and chemoresistance, fuels this complexity. Notch signaling is a known regulator of cancer stem cell (CSC) features in colorectal cancer (CRC), though the effects of its heterogenous signaling on CRC cell stemness are only just emerging. In this review, we discuss how Notch ligand-receptor specificity contributes to regulating stemness, self-renewal, chemoresistance and cancer stem cells heterogeneity in CRC.

Cancer phototherapy with nano-bacteria biohybrids.

The utilization of light for therapeutic interventions, also known as phototherapy, has been extensively employed in the treatment of a wide range of illnesses, including cancer. Despite the benefits of its non-invasive nature, phototherapy still faces challenges pertaining to the delivery of phototherapeutic agents, phototoxicity, and light delivery. The incorporation of nanomaterials and bacteria in phototherapy has emerged as a promising approach that leverages the unique properties of each component. The resulting nano-bacteria biohybrids exhibit enhanced therapeutic efficacy when compared to either component individually. In this review, we summarize and discuss the various strategies for assembling nano-bacteria biohybrids and their applications in phototherapy. We provide a comprehensive overview of the properties and functionalities of nanomaterials and cells in the biohybrids. Notably, we highlight the roles of bacteria beyond their function as drug vehicles, particularly their capacity to produce bioactive molecules. Despite being in its early stage, the integration of photoelectric nanomaterials and genetically engineered bacteria holds promise as an effective biosystem for antitumor phototherapy. The utilization of nano-bacteria biohybrids in phototherapy is a promising avenue for future investigation, with the potential to enhance treatment outcomes for cancer patients.

Pan-cancer analysis identifies the correlations of Thymosin Beta 10 with predicting prognosis and immunotherapy response.

The biological function and prognosis roles of thymosin β(TMSB) 10 are still unclear in pan-cancer. We retrieved The Cancer Genome Atlas and Genotype-tissue expression datasets to obtain the difference of TMSB10 expression between pan-cancer and normal tissues, and analyzed the biological function and prognosis role of TMSB10 in pan-cancer by using cBioPortal Webtool. The expression of TMSB10 in tumor tissues was significantly higher than normal tissues, and showed the potential ability to predict the prognosis of patients in Pan-cancer. It was found that TMSB10 was significantly correlated with tumor microenvironment, immune cell infiltration and immune regulatory factor expression. TMSB10 is involved in the regulation of cellular signal transduction pathways in a variety of tumors, thereby mediating the occurrence of tumor cell invasion and metastasis. Finally, TMSB10 can not only effectively predict the anti-PD-L1 treatment response of cancer patients, but also be used as an important indicator to evaluate the sensitivity of chemotherapy. In vitro, low expression of TMSB10 inhibited clonogenic formation ability, invasion, and migration in glioma cells. Furthermore, TMSB10 may involve glioma immune regulation progression by promoting PD-L1 expression levels via activating STAT3 signaling pathway. Our results show that TMSB10 is abnormally expressed in tumor tissues, which may be related to the infiltration of immune cells in the tumor microenvironment. Clinically, TMSB10 is not only an effective prognostic factor for predicting the clinical treatment outcome of cancer patients, but also a promising biomarker for predicting the effect of tumor immune checkpoint inhibitors (ICIs) and chemotherapy in some cancers.

Abstract 1747: Targeting metabolic and epigenetic programs to re-sensitize glioblastoma to chemotherapy

Abstract Treatment options for glioblastoma (GBM) are limited. Prognosis remains dismal, with an 18 month on average survival rate following diagnosis due to treatment resistance and disease recurrence. The goal of this project is to investigate hallmarks of cancer progression that contribute to temozolomide (TMZ) resistance, a first tine treatment for GBM. Two signaling pathways were investigated in TMZ-sensitive and -resistant GBM cell lines and in primary and recurrent patient-derived xenograft (PDX) tumor cells by genetically and pharmacologically inhibiting methionine adenosyltransferase 2A (MAT2A) and adenosylhomocysteinase (AHCY). Cell growth and survival were assessed by measuring protein expression of proliferation, oxidative stress and cell cycle arrest markers. EPIC array analysis and targeted bisulfite sequencing were conducted to identify changes in genome-wide and specific CpG island methylation. The Seahorse XF Analyzer measured mitochondrial respiratory capacity and oxidative metabolism. Induced pluripotent stem cell organoids were co-cultured with PDX tumor cells to determine if treatments mitigate tumor cell invasiveness. Compared to parental cells (PC), MAT2A gene expression was increased by 1.7-fold in acquired resistant and de novo resistant GBM cells (RC) [(transcript per million): PC, 7386 ± 412; RC, 12941 ± 1023; n=2; p=2.10e-8].Compared to TMZ-sensitive cells (TS), TMZ-resistant cells (TR) demonstrated a 56% increase in baseline oxygen consumption rate [(pmol/min): TS, 179 ± 6.7; TR, 279 ± 13; n=18; p=.0012] and 64% increase in maximal respiratory capacity [(pmol/min): TS, 403 ± 29; TR, 659 ± 35; n=6; p<.0001]. Both primary and recurrent GBM cells were subject to select MAT2A and AHCY inhibitor compounds and EC50s were determined. Recurrent cells demonstrated a vulnerability to TMZ-generated cell death both by genetically knocking down and pharmacologically inhibiting MAT2A and AHCY. MAT2A and AHCY contribute to TMZ resistance and recurrence by dysregulating methylation programs and upregulating antioxidant programs, respectively. These findings provide a foundation for developing novel combinatory therapeutic strategies and inform clinical studies intended to augment the practically negligible rate of remission for GBM and improve treatment outcomes for cancer patients. Citation Format: Emma Rowland, Jordan Walter, Anna Jermakowicz, Robert Suter, Rebecca Riggins, Nagi Ayad. Targeting metabolic and epigenetic programs to re-sensitize glioblastoma to chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1747.

Cancer and COVID-19: A Double Burden on the Healthcare System

The COVID-19 pandemic has placed an unprecedented burden on the healthcare system. In particular, the intersection of COVID-19 and cancer has created a double burden on the healthcare system, presenting challenges in both the diagnosis and treatment of cancer. During the pandemic, overcrowding of hospitals and clinics, shortages of PPE and other medical supplies, and the impact of COVID-19 on healthcare workers have all made it more difficult to care for cancer patients. The challenges in cancer diagnosis and screening during the pandemic have included delays in cancer diagnoses, decreased access to cancer screenings, and a decrease in the number of cancer surgeries being performed. Changes in cancer treatment patterns and access to care during COVID-19 have also impacted the treatment outcomes for cancer patients, with a decrease in the number of cancer patients being treated and an increased risk of poor outcomes for those who are being treated. The impact of COVID-19 on healthcare workers and their ability to care for cancer patients has also been significant, with healthcare workers facing increased exposure to the virus, increased workloads, and increased stress and burnout. The double burden of COVID-19 and cancer on the healthcare system has implications for policy and practice, including the need for improved coordination between cancer and COVID-19 response efforts and the need for increased investment in healthcare infrastructure and resources. In conclusion, the COVID-19 pandemic has created a double burden on the healthcare system, with significant challenges in the diagnosis and treatment of cancer. The impact of COVID-19 on healthcare workers and the healthcare system more broadly highlights the need for improved coordination and increased investment in healthcare resources and infrastructure.

ProTarget: a Danish Nationwide Clinical Trial on Targeted Cancer Treatment based on genomic profiling – a national, phase 2, prospective, multi-drug, non-randomized, open-label basket trial

BackgroundAn increasing number of trials indicate that treatment outcomes in cancer patients with metastatic disease are improved when targeted treatments are matched with druggable genomic alterations in individual patients (pts). An estimated 30–80% of advanced solid tumors harbor actionable genomic alterations. However, the efficacy of personalized cancer treatment is still scarcely investigated in larger, controlled trials due to the low frequency and heterogenous distribution of druggable alterations among different histologic tumor types. Therefore, the overall effect of targeted cancer treatment on clinical outcomes still needs investigation.Study design/methodsProTarget is a national, non-randomized, multi-drug, open-label, pan-cancer phase 2 trial aiming to investigate the anti-tumor activity and toxicity of currently 13 commercially available, EMA-approved targeted therapies outside the labeled indication for treatment of advanced malignant diseases, harboring specific actionable genomic alterations. The trial involves the Danish National Molecular Tumor Board for confirmation of drug-variant matches. Key inclusion criteria include a) measurable disease (RECIST v.1.1), b) ECOG performance status 0–2, and c) an actionable genomic alteration matching one of the study drugs. Key exclusion criteria include a) cancer type within the EMA-approved label of the selected drug, and b) genomic alterations known to confer drug resistance. Initial drug dose, schedule and dose modifications are according to the EMA-approved label. The primary endpoint is objective response or stable disease at 16 weeks. Pts are assigned to cohorts defined by the selected drug, genomic alteration, and tumor histology type. Cohorts are monitored according to a Simon’s two-stage-based design. Response is assessed every 8 weeks for the first 24 weeks, then every 12 weeks. The trial is designed similar to the Dutch DRUP and the ASCO TAPUR trials and is a partner in the Nordic Precision Cancer Medicine Trial Network. In ProTarget, serial fresh tumor and liquid biopsies are mandatory and collected for extensive translational research including whole genome sequencing, array analysis, and RNA sequencing.DiscussionThe ProTarget trial will identify new predictive biomarkers for targeted treatments and provide new data and essential insights in molecular pathways involved in e.g., resistance mechanisms and thereby potentially evolve and expand the personalized cancer treatment strategy.Protocol version: 16, 09-MAY-2022.Trial registrationClinicalTrials.gov Identifier: NCT04341181.Secondary Identifying No: ML41742.EudraCT No: 2019–004771-40.

Predictors of Hypersensitivity Reactions to Platinum-Based Chemotherapy in a Tertiary Care Hospital in Oman: A case control study.

This study aimed to estimate the prevalence and evaluate risk factors of hypersensitivity reactions (HSRs) to platinum-based compounds (PBCs) in cancer patients. PBCs play an important role in cancer therapy. However, one of the drawbacks of PBCs is the occasional occurrence of HSRs, which can lead to serious consequences. This retrospective case control study was conducted from January 2013 to December 2020 at Sultan Qaboos University Hospital, Muscat, Oman and included patients who received any PBC for the management of non-haematological cancers. Data regarding demographic characteristics and diseases and treatment details were collected from the hospital's electronic database. The data were quantitatively described and Student's t-test and Wilcoxon Mann-Whitney tests were used to detect significant differences. A total of 38 cases and 148 matched controls were studied. The prevalence of HSRs to PBCs in the cohort of this study was 4.7% (95% confidence interval: 3.33-6.37%), higher with carboplatin compared with cisplatin and oxaliplatin. The female gender (P = 0.032), concomitant taxanes (P = 0.002) and concurrent radiation (P <0.001) were significant predictors of HSRs to PBCs. The majority of the reactions were of mild to moderate severity, and the rechallenge rate after HSR development was 13%. HSRs to PBCs impact therapy decisions and understanding the risk factors is important to improve treatment outcomes in cancer patients.

The crosstalk between the gut microbiota and tumor immunity: Implications for cancer progression and treatment outcomes.

The gastrointestinal tract is inhabited by trillions of commensal microorganisms that constitute the gut microbiota. As a main metabolic organ, the gut microbiota has co-evolved in a symbiotic relationship with its host, contributing to physiological homeostasis. Recent advances have provided mechanistic insights into the dual role of the gut microbiota in cancer pathogenesis. Particularly, compelling evidence indicates that the gut microbiota exerts regulatory effects on the host immune system to fight against cancer development. Some microbiota-derived metabolites have been suggested as potential activators of antitumor immunity. On the contrary, the disequilibrium of intestinal microbial communities, a condition termed dysbiosis, can induce cancer development. The altered gut microbiota reprograms the hostile tumor microenvironment (TME), thus allowing cancer cells to avoid immunosurvelliance. Furthermore, the gut microbiota has been associated with the effects and complications of cancer therapy given its prominent immunoregulatory properties. Therapeutic measures that aim to manipulate the interplay between the gut microbiota and tumor immunity may bring new breakthroughs in cancer treatment. Herein, we provide a comprehensive update on the evidence for the implication of the gut microbiota in immune-oncology and discuss the fundamental mechanisms underlying the influence of intestinal microbial communities on systemic cancer therapy, in order to provide important clues toward improving treatment outcomes in cancer patients.

Myths, beliefs, and attitude toward cancer among the family caregivers of cancer patients: A community-based, mixed-method study in rural Tamil Nadu.

Family support is one of the most crucial components of cancer care. The familial beliefs and myths associated with cancer can seriously affect the quality of life and treatment outcome of cancer patients. This study intends to explore the prevailing myths, beliefs, and attitude toward cancer among the family caregivers of cancer patients. A community-based, exploratory, mixed-method study was conducted among family caregivers of cancer patients in Cuddalore and Villupuram districts of Tamil Nadu. Content analysis method was used for in-depth interviews. Sociodemographic characteristics and attitude of the study participants were described using proportions. A common myth about causation of cancer was that it was contagious or of infective origin. Disbelief in tobacco's causation of cancer was found among the study participants. Family members' support was viewed as an essential component for cancer patients. Majority of the participants in the quantitative survey showed favorable attitude toward cancer patients. The common misconception about cancer treatment was that surgery/biopsy can spread cancer and herbal products can cure cancer. Even though a majority of the participants showed favorable attitude toward their cancer patients, false beliefs and myths regarding causation and treatment of cancer are prevalent in the community.

Parallel single-cell and bulk transcriptome analyses reveal key features of the gastric tumor microenvironment

BackgroundThe tumor microenvironment (TME) has been shown to strongly influence treatment outcome for cancer patients in various indications and to influence the overall survival. However, the cells forming the TME in gastric cancer have not been extensively characterized.ResultsWe combine bulk and single-cell RNA sequencing from tumors and matched normal tissue of 24 treatment-naïve GC patients to better understand which cell types and transcriptional programs are associated with malignant transformation of the stomach. Clustering 96,623 cells of non-epithelial origin reveals 81 well-defined TME cell types. We find that activated fibroblasts and endothelial cells are most prominently overrepresented in tumors. Intercellular network reconstruction and survival analysis of an independent cohort imply the importance of these cell types together with immunosuppressive myeloid cell subsets and regulatory T cells in establishing an immunosuppressive microenvironment that correlates with worsened prognosis and lack of response in anti-PD1-treated patients. In contrast, we find a subset of IFNγ activated T cells and HLA-II expressing macrophages that are linked to treatment response and increased overall survival.ConclusionsOur gastric cancer single-cell TME compendium together with the matched bulk transcriptome data provides a unique resource for the identification of new potential biomarkers for patient stratification. This study helps further to elucidate the mechanism of gastric cancer and provides insights for therapy.

Factors Affecting the Outcome of the Operable Subtype Luminal B Breast Cancer Treatment

Breast cancer is a condition of uncontrolled breast cell proliferation that most frequently develops from the ductal epithelial cells (85%) or lobules (15%) of the breast glands. Poor prognoses for patients can result from cancer's extensive organ metastasis, now the second largest cause of cancer death in women. This study aims to identify the variables that affect how well patients with the operable breast cancer subtype Luminal B respond to treatment at RSUP DR M Djamil Padang. This research used a cross-sectional methodology with a retrospective study approach to identify characteristics that affect the treatment outcome for operable breast cancer subtype luminal B at RSUP DR. M. Djamil Padang. From August to November 2022, the study was carried out in the Oncology Surgery Division of RSUP DR. M. Djamil Padang. With HER2 being the main component, multivariate analysis revealed that HER2 and the kind of therapy were significantly connected with the treatment outcome for cancer patients.