Monitoring Of Therapeutic Response Research Articles

Impact of HER2-targeted PET/CT imaging in patients with breast cancer and therapeutic response monitoring.

Patients with breast cancer exhibit heterogeneity in the expression of the human epithelial growth factor receptor 2 (HER2). Clinically, re-biopsying recurrent or metastatic lesions presents substantial challenges. This study aimed to evaluate the efficacy of HER2-targeted PET/CT imaging in identifying HER2 expression in breast cancer lesions and monitoring therapeutic responses. This exploratory analysis used data from a prospective study that included adult patients with breast cancer who underwent both Al18F-NOTA-HER2-BCH and 18F-FDG PET/CT imaging at Beijing Cancer Hospital between June 2020 and July 2023 (NCT04547309). Fifty-nine participants, with a median age of 55 years, were analyzed. Lesions imaged with HER2-targeted PET/CT before anti-HER2 therapy exhibited higher SUVmax values than after therapy in HER2 immunohistochemistry (IHC) 3 + lesions (19.9, 95% CI: 15.7-25.3 vs 9.8, 95% CI: 5.6-14.7; P = .006). A significant positive correlation was observed between SUVmax on HER2-targeted PET/CT and IHC before therapy (P = .034), with higher SUVmax values noted in lesions with positive HER2 pathology compared to those with negative HER2 status (17.9 ± 13.2 vs 1.1 ± 0.3; P = .007). HER2 expression heterogeneity was confirmed both between primary and metastatic lesions (22.9%) and among different metastatic sites (26.7%) as assessed by HER2-targeted PET/CT. A superior therapeutic response correlated with higher pretreatment SUVmax values. The HER2-targeted PET/CT procedure was well-tolerated by all patients. HER2-targeted PET/CT imaging offers a practical, non-invasive, and quantitative approach for assessing HER2 status in breast cancer patients, facilitating the optimization and personalization of therapeutic strategies by oncologists.

ImmunoPET imaging of LAG-3 expression in tumor microenvironment with 68Ga-labelled cyclic peptides tracers: from bench to bedside

BackgroundLymphocyte activation gene 3 (LAG-3) has been considered as the next generation of immune checkpoint and a promising prognostic biomarker of immunotherapy. As with programmed cell death protein-1/programmed death-ligand 1...

The Role of Biomarkers in HPV-Positive Head and Neck Squamous Cell Carcinoma: Towards Precision Medicine.

Head and neck cancer (HNC) represents a significant global health challenge, with squamous cell carcinomas (SCCs) accounting for approximately 90% of all HNC cases. These malignancies, collectively referred to as head and neck squamous cell carcinoma (HNSCC), originate from the mucosal epithelium lining the larynx, pharynx, and oral cavity. The primary risk factors associated with HNSCC in economically disadvantaged nations have been chronic alcohol consumption and tobacco use. However, in more affluent countries, the landscape of HNSCC has shifted with the identification of human papillomavirus (HPV) infection, particularly HPV-16, as a major risk factor, especially among nonsmokers. Understanding the evolving risk factors and the distinct biological behaviors of HPV-positive and HPV-negative HNSCC is critical for developing targeted treatment strategies and improving patient outcomes in this complex and diverse group of cancers. Accurate diagnosis of HPV-positive HNSCC is essential for developing a comprehensive model that integrates the molecular characteristics, immune microenvironment, and clinical outcomes. The aim of this comprehensive review was to summarize the current knowledge and advances in the identification of DNA, RNA, and protein biomarkers in bodily fluids and tissues that have introduced new possibilities for minimally or non-invasive cancer diagnosis, monitoring, and assessment of therapeutic responses.

The Role of Biomarkers in HPV-Positive Head and Neck Squamous Cell Carcinoma: Towards Precision Medicine

Head and neck cancer (HNC) represents a significant global health challenge, with squamous cell carcinomas (SCCs) accounting for approximately 90% of all HNC cases. These malignancies, collectively referred to as head and neck squamous cell carcinoma (HNSCC), originate from the mucosal epithelium lining the larynx, pharynx, and oral cavity. The primary risk factors associated with HNSCC in economically disadvantaged nations have been chronic alcohol consumption and tobacco use. However, in more affluent countries, the landscape of HNSCC has shifted with the identification of human papillomavirus (HPV) infection, particularly HPV-16, as a major risk factor, especially among nonsmokers. Understanding the evolving risk factors and the distinct biological behaviors of HPV-positive and HPV-negative HNSCC is critical for developing targeted treatment strategies and improving patient outcomes in this complex and diverse group of cancers. Accurate diagnosis of HPV-positive HNSCC is essential for developing a comprehensive model that integrates the molecular characteristics, immune microenvironment, and clinical outcomes. The aim of this comprehensive review was to summarize the current knowledge and advances in the identification of DNA, RNA, and protein biomarkers in bodily fluids and tissues that have introduced new possibilities for minimally or non-invasive cancer diagnosis, monitoring, and assessment of therapeutic responses.

Reflectance confocal microscopy for plaque psoriasis therapeutic follow-up during an anti-interleukin-17A monoclonal antibody: an observational study

Interleukin-17A therapeutic inhibitors are among the most effective treatment methods for moderate-to-severe plaque psoriasis (PP). Reflectance confocal microscopy is a non-invasive imaging technique already documented to be beneficial in evaluating the follow-up of PP under treatment with topical actives and phototherapy. This study aimed to assess the epidermal and dermal changes associated with psoriasis and its treatment with RCM during systemic secukinumab treatment in patients with moderate-to-severe PP. A pilot study was conducted to evaluate RCM as a non-invasive tool for monitoring secukinumab treatment in patients with PP. For patients receiving secukinumab treatment, lesional skin was selected for RCM imaging, which were recorded at all scheduled times. The RCM evaluation criteria were established based on the histopathological diagnostic criteria for psoriasis. The clinical severity of psoriasis was assessed utilizing the psoriasis area severity index. A total of 23 patients with PP were included in the study. Each patient received 300 mg of subcutaneous secukinumab as induction therapy at baseline and weeks 1–4, followed by maintenance therapy every four weeks. Microscopic confocal changes were observed during the treatment. The results identified early microscopic evidence of the anti-inflammatory activity of secukinumab, which was not detected during the clinical examination. RCM findings correlating with the PASI were used to observe the patient’s response to treatment and were identified as follows: acanthosis and parakeratosis, presence of epidermal and dermal inflammatory cells, presence of non-edge dermal papillae, and vascularization in the papillary dermis. This study is the first to demonstrate the use of RCM as an effective tool for non-invasive monitoring of secukinumab therapeutic response at a cellular level in a clinical or research setting. Early detection of RCM parameters associated with secukinumab activity may facilitate the identification of an early treatment response. RCM appears to be capable of providing practical and helpful information regarding follow-up in patients with PP undergoing secukinumab treatment. RCM may also provide novel perspectives on the subclinical evaluation of PP’s response to biological therapy.

Identification of Circular RNAs as Biomarker Candidates in Lung Cancer Treatment.

Lung cancer is the most common malignancy and among the leading cause of cancer death worldwide. Therefore, there is an important need for biomarkers that can be used in the early diagnosis of the disease and in the follow-up of treatment. Circular RNAs (circRNAs) have a covalently closed circular structure that lacks 3' and 5' polar ends and is resistant to RNAase enzymes. Due to these properties, they can be stably found in body fluids. Therefore, they can serve as potential biomarkers in the diagnosis, monitoring of therapeutic response and prognosis of cancer. In our study, we aimed to investigate the expression levels of circRNA molecules in the treatment of lung cancer and to determine those that have the potential to be biomarkers. In this in vitro study, expression levels of 163 circRNAs were investigated in A549 cells, a non-small cell lung cancer cell line, before and after treatment with carboplatin and pemetrexed. Total RNA isolation and cDNA synthesis were performed after treatments. Expression levels of circRNA genes were determined by RT-qPCR method with the designed divergent primer sequences. The study revealed the characterisation of differentially expressed circRNAs by treatment in lung cancer cells. Of them, hsa_circ_0001320 is not expressed in cancer cells, is expressed only after treatment, and increased the level of its expression in response to combination therapy. As a result, while carboplatin, pemetrexed, and combined drug applications changed the expression levels of some circRNAs in lung cancer cells, some circRNAs were expressed only after treatment. In treatment follow-up and management, hsa_circ_0001320 has been identified as potential biomarker candidate.

Macromolecular Biomaterials Endowed Strategies for Synergistic Treatment of Psoriasis: Recent Advancements and Future Prospects

Psoriasis is a chronic autoimmune skin disorder that affects millions of individuals worldwide, causing discomfort and significantly impacting their quality of life. Recent advancements in the field of biomaterials and drug delivery have opened up promising avenues for the treatment of psoriasis. This manuscript summarizes key developments in the use of biomaterials and innovative drug delivery strategies to enhance the management of psoriasis. Biomaterials offer a versatile platform for the localized and sustained delivery of therapeutic agents to psoriatic lesions. Biocompatible materials, such as hydrogels and nanoparticles, have been engineered to encapsulate drugs and biologics, providing controlled release kinetics that maximize drug efficacy while minimizing systemic side effects. These biomaterial-based delivery systems have demonstrated remarkable potential in targeting the pathological mechanisms underlying psoriasis, including inflammation, hyperproliferation of keratinocytes and abnormal immune responses. In addition, recent advancements in personalized medicine have allowed for the tailoring of drug formulations to individual patient needs, optimizing treatment outcomes. Emerging technologies, such as 3D bioprinting, enable the creation of patient-specific skin models for drug screening, promoting the development of precision therapies. Future prospects in this field include the integration of smart biomaterials that respond to disease-specific cues, enabling on-demand drug release and real-time monitoring of therapeutic responses.

Methotrexate-loaded manganese nitrogen dual-doped carbon quantum dots as targeted nano drug-delivery system for potential use in cancer theranostics

The present work highlights manganese nitrogen dual-doped carbon quantum dots as a novel pH-sensitive drug delivery system, for the delivery of methotrexate, targeted to cancer cells, along with the simultaneous real-time monitoring of cellular uptake and drug delivery using fluorescence imaging. Briefly, methotrexate was conjugated with the as-prepared quantum dots to form a nano drug-delivery system through non-covalent interactions. The developed material demonstrated drug loading efficiency of ∼91 % and a very efficient (∼80 %) pH-responsive drug release at pH 5.5. The cytotoxic properties of the developed nano-platform viz. manganese, nitrogen dual-doped carbon quantum dots, and methotrexate conjugated manganese nitrogen dual-doped carbon quantum dot complex were evaluated in cancer cells (HeLa) and healthy human cells (L929). The conjugated complex demonstrated excellent biocompatibility, high cellular uptake, and a substantial drug release. Healthy human cells were largely unaffected when incubated with both the MTX-conjugated Mn-, N-CQD and the free drug. Additionally, in vitro, the fluorescence bio-imaging potential of the developed nano-platform was also assessed, where the unconjugated (free) quantum dots exhibited better blue fluorescence imaging potential compared to that of the conjugated complex, which can be attributed to fluorescence quenching due to the presence of methotrexate. This study highlights the manganese nitrogen dual-doped carbon quantum dots capable of pH-responsive methotrexate drug delivery selective to cancer cells. The combination of drug delivery and fluorescence imaging creates an efficient platform for targeted therapy, allowing very precise drug release while accessing non-invasive monitoring of therapeutic response. This method holds a great promise for advancing cancer treatment strategies, with the potential for increased efficacy and decreased side effects.

Deep Learning in Breast Cancer Imaging: State of the Art and Recent Advancements in Early 2024.

The rapid advancement of artificial intelligence (AI) has significantly impacted various aspects of healthcare, particularly in the medical imaging field. This review focuses on recent developments in the application of deep learning (DL) techniques to breast cancer imaging. DL models, a subset of AI algorithms inspired by human brain architecture, have demonstrated remarkable success in analyzing complex medical images, enhancing diagnostic precision, and streamlining workflows. DL models have been applied to breast cancer diagnosis via mammography, ultrasonography, and magnetic resonance imaging. Furthermore, DL-based radiomic approaches may play a role in breast cancer risk assessment, prognosis prediction, and therapeutic response monitoring. Nevertheless, several challenges have limited the widespread adoption of AI techniques in clinical practice, emphasizing the importance of rigorous validation, interpretability, and technical considerations when implementing DL solutions. By examining fundamental concepts in DL techniques applied to medical imaging and synthesizing the latest advancements and trends, this narrative review aims to provide valuable and up-to-date insights for radiologists seeking to harness the power of AI in breast cancer care.

Ex vivo precision-cut liver slices model disease phenotype and monitor therapeutic response for liver monogenic diseases.

In academic research and the pharmaceutical industry, in vitro cell lines and in vivo animal models are considered as gold standards in modelling diseases and assessing therapeutic efficacy. However, both models have intrinsic limitations, whilst the use of precision-cut tissue slices can bridge the gap between these mainstream models. Precision-cut tissue slices combine the advantage of high reproducibility, studying all cell sub-types whilst preserving the tissue matrix and extracellular architecture, thereby closely mimicking a mini-organ. This approach can be used to replicate the biological phenotype of liver monogenic diseases using mouse models. Here, we describe an optimised and easy-to-implement protocol for the culture of sections from mouse livers, enabling its use as a reliable ex-vivo model to assess the therapeutic screening of inherited metabolic diseases. We show that precision-cut liver sections can be a reliable model for recapitulating the biological phenotype of inherited metabolic diseases, exemplified by common urea cycle defects such as citrullinemia type 1 and argininosuccinic aciduria, caused by argininosuccinic synthase (ASS1) and argininosuccinic lyase (ASL) deficiencies respectively. Therapeutic response to gene therapy such as messenger RNA replacement delivered via lipid nanoparticles can be monitored, demonstrating that precision-cut liver sections can be used as a preclinical screening tool to assess therapeutic response and toxicity in monogenic liver diseases.

Pushing the Boundaries of Liquid Biopsies for Early Precision Intervention.

Liquid biopsies are emerging as powerful minimally invasive approaches that have the potential to solve several long-standing problems spanning the continuum of cancer care: early detection of cancer, minimal residual disease tracking, and refinement of the heterogeneity of clinical responses together with therapeutic response monitoring in the metastatic setting. Existing challenges driven by technical limitations and establishment of the clinical value of liquid biopsies represent fields of active research that call for convergence science approaches to bridge scientific discovery with clinical care.

Thermophoretic glycan profiling of extracellular vesicles for triple-negative breast cancer management

Triple-negative breast cancer (TNBC) is a highly metastatic and heterogeneous type of breast cancer with poor outcomes. Precise, non-invasive methods for diagnosis, monitoring and prognosis of TNBC are particularly challenging due to a paucity of TNBC biomarkers. Glycans on extracellular vesicles (EVs) hold the promise as valuable biomarkers, but conventional methods for glycan analysis are not feasible in clinical practice. Here, we report that a lectin-based thermophoretic assay (EVLET) streamlines vibrating membrane filtration (VMF) and thermophoretic amplification, allowing for rapid, sensitive, selective and cost-effective EV glycan profiling in TNBC plasma. A pilot cohort study shows that the EV glycan signature reaches 91% accuracy for TNBC detection and 96% accuracy for longitudinal monitoring of TNBC therapeutic response. Moreover, we demonstrate the potential of EV glycan signature for predicting TNBC progression. Our EVLET system lays the foundation for non-invasive cancer management by EV glycans.

Identification of Serum Biomarkers to Monitor Therapeutic Response in Intestinal-Type Gastric Cancer.

There are a limited number of clinically useful serum biomarkers to predict tumor onset or treatment response in gastric cancer (GC). For this reason, we explored the serum proteome of the gp130Y757F murine model of intestinal-type gastric cancer (IGC). We identified 30 proteins with significantly elevated expression in early gp130Y757F IGC and 12 proteins that were significantly elevated in late gp130Y757F IGC compared to age- and gender-matched wild-type mice. Within these signatures, there was an overlap of 10 proteins commonly elevated in both early- and late-stage disease. These results highlight the potential to identify serum biomarkers of disease stage. Since IGC in the gp130Y757F model can be reversed following therapeutic inhibition of Interleukin (IL)-11, we explored whether the protein signatures we identified could be used to monitor tumor regression. We compared two different therapeutic modalities and found 5 proteins to be uniquely differentially expressed between control animals and animals halfway through treatment, with 10 differentially expressed at the end of treatment. Our findings highlight the potential to identify reliable biomarkers to track IGC tumor regression in response to treatment.

MicroRNAs in Testicular Germ Cell Tumors: The Teratoma Challenge.

Testicular germ cell tumors (TGCTs) are relatively common in young men, making accurate diagnosis and prognosis assessment essential. MicroRNAs (miRNAs), including microRNA-371a-3p (miR-371a-3p), have shown promise as biomarkers for TGCTs. This review discusses the recent advancements in the use of miRNA biomarkers in TGCTs, with a focus on the challenges surrounding the noninvasive detection of teratomas. Circulating miR-371a-3p, which is expressed in undifferentiated TGCTs but not in teratomas, is a promising biomarker for TGCTs. Its detection in serum, plasma, and, potentially, cystic fluid could be useful for TGCT diagnosis, surveillance, and monitoring of therapeutic response. Other miRNAs, such as miR-375-3p and miR-375-5p, have been investigated to differentiate between TGCT subtypes (teratoma, necrosis/fibrosis, and viable tumors), which can aid in treatment decisions. However, a reliable marker for teratoma has yet to be identified. The clinical applications of miRNA biomarkers could spare patients from unnecessary surgeries and allow for more personalized therapeutic approaches. Particularly in patients with residual masses larger than 1 cm following chemotherapy, it is critical to differentiate between viable tumors, teratomas, and necrosis/fibrosis. Teratomas, which mimic somatic tissues, present a challenge in differentiation and require a comprehensive diagnostic approach. The combination of miR-371 and miR-375 shows potential in enhancing diagnostic precision, aiding in distinguishing between teratomas, viable tumors, and necrosis. The implementation of miRNA biomarkers in TGCT care could improve patient outcomes, reduce overtreatment, and facilitate personalized therapeutic strategies. However, a reliable marker for teratoma is still lacking. Future research should focus on the clinical validation and standardization of these biomarkers to fully realize their potential.

Current Approaches for Monitoring of Patients with Inflammatory Bowel Diseases: A Narrative Review.

Patients with inflammatory bowel diseases (IBD) require proactive monitoring both during the active phase to evaluate therapeutic response and during the remission phase to evaluate relapse or colorectal cancer surveillance. However, monitoring may vary between patients with ulcerative colitis (UC) and Crohn's disease (CD), with distinct tools and intervals. This narrative review aims to focus on modern approaches to IBD monitoring, considering international guidelines and expert consensus. The most recent European diagnostic guidelines advocate a combination of clinical, laboratory, endoscopic, and radiological parameters to evaluate the disease course of patients with IBD. Unfortunately, the conventional symptom-based therapeutic approach does not improve long-term outcomes and there is no single ideal biomarker available. Endoscopy plays a key role in evaluating response to therapy as well as monitoring disease activity. Recently, bedside intestinal ultrasound (IUS) has gained increasing interest and diffusion as it appears to offer several advantages including the monitoring of therapeutic response. In light of growing clinical advances, we present a schematic evidence-based monitoring algorithm that can be easily applied in clinical practice which combines all major monitoring modalities, including noninvasive tools such as IUS and video-capsule endoscopy.

A continuous flow bioreactor system for high-throughput hyperpolarized metabolic flux analysis.

Hyperpolarized carbon-13 labeled compounds are increasingly being used in medical MR imaging (MRI) and MR imaging (MRI) and spectroscopy (MRS) research, due to its ability to monitor tissue and cell metabolism in real-time. Although radiological biomarkers are increasingly being considered as clinical indicators, biopsies are still considered the gold standard for a large variety of indications. Bioreactor systems can play an important role in biopsy examinations because of their ability to provide a physiochemical environment that is conducive for therapeutic response monitoring ex vivo. We demonstrate here a proof-of-concept bioreactor and microcoil receive array setup that allows for ex vivo preservation and metabolic NMR spectroscopy on up to three biopsy samples simultaneously, creating an easy-to-use and robust way to simultaneously run multisample carbon-13 hyperpolarization experiments. Experiments using hyperpolarized [1-13C]pyruvate on ML-1 leukemic cells in the bioreactor setup were performed and the kinetic pyruvate-to-lactate rate constants ( ) extracted. The coefficient of variation of the experimentally found s for five repeated experiments was . With this statistical power, treatment effects of 30%-40% change in lactate production could be easily differentiable with only a few hyperpolarization dissolutions on this setup. Furthermore, longitudinal experiments showed preservation of ML-1 cells in the bioreactor setup for at least 6 h. Rat brain tissue slices were also seen to be preserved within the bioreactor for at least 1 h. This validation serves as the basis for further optimization and upscaling of the setup, which undoubtedly has huge potential in high-throughput studies with various biomarkers and tissue types.

P421 The faecal biomarker LDN-051 is a novel tool for monitoring disease activity and therapeutic response in Inflammatory Bowel Diseases

Abstract Background Crohn’s disease and ulcerative colitis, two forms of inflammatory bowel disease (IBD) require lifelong treatment and patient monitoring. Current predictors of relapse and therapeutic success have limitations, therefore there is high unmet need to identify novel biomarkers in IBD. Monitoring approaches for IBD are mostly invasive, time-consuming, and expensive. Therefore, a simple, rapid, and non-invasive test, with ability to differentiate IBD from other gastrointestinal conditions and to monitor disease activity, will have important clinical implications. Our previous mucosal cytokine profiling identified that Plasminogen activator inhibitor type 1 (PAI-1) is expressed in IBD patients with active disease, but not in control. Therefore, our aim was to assess the utility of PAI-1 in monitoring disease activity and therapeutic response of IBD patients in different biological samples. Methods Serum, biopsy and faecal samples were collected from 132 IBD patients and 30 controls without IBD. ELISA method was used to define the level of PAI-1 in the mucosa, serum, and faecal samples and the serum CRP levels were also determined. For the mucosal gene expression analysis qRT-PCR was used. The correlation and ROC analyses were applied to observe the relationship between the disease activity and PAI-1 level. Results The applied screening approach detected significant higher expression of PAI-1 in active IBD. We demonstrated that the serum, mucosal and faecal PAI-1 concentration was significantly elevated in IBD patients showing clinical and endoscopic activity. Additionally, in responder patients the initial PAI-1 level decreased significantly upon successful therapy, whereas it remained unchanged in non-responders. We also showed that faecal PAI-1 selectively increases in active IBD patients, but not in other organic gastrointestinal diseases. In addition, the stability analysis of faecal PAI-1 showed that the protein was detectable up to one week at room temperature and 4ºC. The serum, mucosal and faecal PAI-1 level showed positive correlation to the endoscopic activity. ROC curves demonstrated that faecal PAI-1 showed a relatively high power to distinguish between active and control patients. However, the serum CRP level no reflected to the therapeutic response. Conclusion Our results suggest that serum, mucosal and faecal PAI-1 expression reflects to the disease activity in IBD, which could be used to disease monitoring and possibly therapeutic response. The correlation between the faecal PAI-1 level and the endoscopic activity promotes that it could be used as a novel non-invasive disease specific faecal biomarker in the IBD diagnosis.

Clinical validation of Northstar Response, a novel methylated ctDNA therapy response monitoring assay in patients with advanced GI cancer undergoing active treatment.

756 Background: ctDNA is a non-invasive way to holistically assess the tumor. Several assays developed for therapy response monitoring rely on variant allele frequencies to detect scarce somatic variants in the blood. In contrast, methylated ctDNA measurement has shown promise as a treatment monitoring biomarker without requiring a tumor biopsy, yet accuracy is limited in ability to precisely quantify the amount of methylation present in the ctDNA. The CLIA-approved Northstar Response assay (BillionToOne, Inc.) quantifies on average 90 methylated loci, a 10-fold increase in signal over the average tissue-informed assays. Methods: This prospective, observational study assesses the clinical validity of Northstar Response, a quantitative methylated ctDNA therapeutic response monitoring assay that does not require prior tumor tissue. A cohort of 100 advanced cancer patients with a variety of GI malignancies submit serial ctDNA measurements in a blinded fashion. Eligibility includes advanced GI cancer patients starting a new line of systemic therapy (IO, targeted, chemo or combination) who are not pregnant or s/p organ or bone marrow transplantation. Blood samples are collected at baseline, at the time of imaging, and at least two intermediate time points (~30 days and 60 days post tx initiation). The primary endpoint is to measure the concordance and temporal relationship between disease progression measured by ctDNA compared to RECISTv1.1, clinical confirmation, or death. A Cox proportional hazards model will be used to quantify the association between the change in tumor methylation score (TMS; total methylated tumor molecules per 1000 assayed genomic equivalents) and clinical progression. The cohort will be split equally between a training and validation set. Results: Enrollment began in June 2023 and continues. To date, 28 patients with a variety of advanced GI cancers (table) have been enrolled with 37 samples processed. All samples have passed established QC metrics with average turn-around-time from receipt of sample to final report of 9.1 days (95% were <15 days). TMS ranged from <120 to >160,000 across individual samples, indicating that the assay can detect a broad range of tumor load in blood. We detected a median of 69 methylated loci per sample (range 4-451). Out of 21 pts, 17 had at least one sample with TMS measured above the noise floor of 120. Conclusions: The Northstar Response assay can consistently detect ctDNA across a variety of advanced GI cancers. Enrollment continues with formal comparison to clinical progression planned. Additional data on the complete training set will be available at the meeting.[Table: see text]

NIR-Triggered Thermosensitive Nanoreactors for Dual-Guard Mechanism-Mediated Precise and Controllable Cancer Chemo-Phototherapy.

Thermosensitive nanoparticles can be activated by externally applying heat, either through laser irradiation or magnetic fields, to trigger the release of drug payloads. This controlled release mechanism ensures that drugs are specifically released at the tumor site, maximizing their effectiveness while minimizing systemic toxicity and adverse effects. However, its efficacy is limited by the low concentration of drugs at action sites, which is caused by no specific target to tumor sties. Herein, hyaluronic acid (HA), a gooey, slippery substance with CD44-targeting ability, was conjugated with a thermosensitive polymer poly(acrylamide-co-acrylonitrile) to produce tumor-targeting and thermosensitive polymeric nanocarrier (HA-P) with an upper critical solution temperature (UCST) at 45 °C, which further coloaded chemo-drug doxorubicin (DOX) and photosensitizer Indocyanine green (ICG) to prepare thermosensitive nanoreactors HA-P/DOX&ICG. With photosensitizer ICG acting as the "temperature control element", HA-P/DOX&ICG nanoparticles can respond to temperature changes when receiving near-infrared irradiation and realize subsequent structure depolymerization for burst drug release when the ambient temperature was above 45 °C, achieving programmable and on-demand drug release for effective antitumor therapy. Tumor inhibition rate increased from 61.8 to 95.9% after laser irradiation. Furthermore, the prepared HA-P/DOX&ICG nanoparticles possess imaging properties, with ICG acting as a probe, enabling real-time monitoring of drug distribution and therapeutic response, facilitating precise treatment evaluation. These results provide enlightenment for the design of active tumor targeting and NIR-triggered programmable and on-demand drug release of thermosensitive nanoreactors for tumor therapy.

Ovarian Cancer Diagnosis and Prognosis Based on Cell-Free DNA Methylation.

Background:Ovarian cancer stands as the deadliest malignant tumor within the female reproductive tract. As a result of the absence of effective diagnostic and monitoring markers, 75% of ovarian cancer cases are diagnosed at a late stage, leading to a mere 50% survival rate within five years. The advancement of molecular biology is essential for accurate diagnosis and treatment of ovarian cancer.Methods:A review of several randomized clinical trials, focusing on the ovarian cancer, was undertaken. The advancement of molecular biology and diagnostic methods related to accurate diagnosis and treatment of ovarian cancer were examined. Results:Liquid biopsy is an innovative method of detecting malignant tumors that has gained increasing attention over the past few years. Cell-free DNA assay-based liquid biopsies show potential in delineating tumor status heterogeneity and tracking tumor recurrence. DNA methylation influences a multitude of biological functions and diseases, especially during the initial phases of cancer. The cell-free DNA methylation profiling system has emerged as a sensitive and non-invasive technique for identifying and detecting the biological origins of cancer. It holds promise as a biomarker, enabling early screening, recurrence monitoring, and prognostic evaluation of cancer. Conclusions:This review evaluates recent advancements and challenges associated with cell-free DNA methylation analysis for the diagnosis, prognosis monitoring, and assessment of therapeutic responses in the management of ovarian cancers, aiming to offer guidance for precise diagnosis and treatment of this disease.