Cancer Therapy Research Articles

Hybrid Nanogel-Wrapped Anisotropic Gold Nanoparticles Feature Enhanced Photothermal Stability.

Anisotropic gold nanoparticles (AuNPs) are renowned for their unique properties - including localized surface plasmon resonance (LSPR) and adjustable optical responses to light exposure - that enable the conversion of light into heat and make them a promising tool in cancer therapy. Nonetheless, their tendency to aggregate and consequently lose their photothermal conversion capacity during prolonged irradiation periods represents a central challenge in developing anisotropic AuNPs for clinical use. To overcome this issue, an innovative approach that facilitates the encapsulation of individual anisotropic AuNPs within thin nanogels, forming hybrid nanomaterials that mirror the inorganic core's morphology while introducing a negligible (2-8nm) increase in overall diameter is proposed. The encapsulation of rod- and star-shaped anisotropic AuNPs within poly-acrylamide (pAA) or poly-(N-isopropylacrylamide) (pNIPAM) nanogels is successfully demonstrated. The ultrathin polymeric layers display remarkable durability, significantly enhancing the photothermal stability of anisotropic AuNPs during their interaction with near-infrared light and effectively boosting their photothermal capacities for extended irradiation periods. The outcomes of the research thus support the development of more stable and reliable AuNPs as hybrid nanomaterials, positioning them as promising nanomedicinal platforms.

Next-Generation Therapeutic Antibodies for Cancer Treatment: Advancements, Applications, and Challenges.

The field of cancer treatment has evolved significantly over the last decade with the emergence of next-generation therapeutic antibodies. Conventional treatments like chemotherapy pose significant challenges, including adverse side effects. Monoclonal antibodies have paved the way for more targeted and effective interventions. The evolution from chimeric to humanized and fully human antibodies has led to a reduction in immunogenicity and enhanced tolerance in vivo. The advent of next-generation antibodies, including bispecific antibodies, nanobodies, antibody-drug conjugates, glyco-engineered antibodies, and antibody fragments, represents a leap forward in cancer therapy. These innovations offer increased potency, adaptability, and reduced drug resistance. Challenges such as target validation, immunogenicity, and high production costs exist. However, technological advancements in antibody engineering techniques provide optimism for addressing these issues. The future promises a paradigm shift, where ongoing research will propel these powerful antibodies to the forefront, revolutionizing the fight against cancer and creating new preventive and curative treatments. This review provides an overview of three next-generation antibody-based molecules, namely bispecific antibodies, antibody-drug conjugates, and nanobodies that have shown promising results in cancer treatment. It discusses the evolution of antibodies from conventional forms to next-generation molecules, along with their applications in cancer treatment, production methods, and associated challenges. The review aims to offer researchers insights into the evolving landscape of next-generation antibody-based cancer therapeutics and their potential to revolutionize treatment strategies.

Multi-omics and clustering analyses reveal the mechanisms underlying unmet needs for patients with lung adenocarcinoma and identify potential therapeutic targets.

The cancer genome contains several driver mutations. However, in some cases, no known drivers have been identified; these remaining areas of unmet needs, leading to limited progress in cancer therapy. Whole-genome sequencing (WGS) can identify non-coding alterations associated with the disease. Consequently, exploration of non-coding regions using WGS and other omics data such as ChIP-sequencing (ChIP-seq) to discern novel alterations and mechanisms related to tumorigenesis have been attractive these days. Integrated multi-omics analyses, including WGS, ChIP-seq, DNA methylation, and RNA-sequencing (RNA-seq), were conducted on samples from patients with non-clinically actionable genetic alterations (non-CAGAs) in lung adenocarcinoma (LUAD). Second-level cluster analysis was performed to reinforce the correlations associated with patient survival, as identified by RNA-seq.Subsequent differential gene expression analysis was performed to identify potential druggable targets. Differences in H3K27ac marks in non-CAGAs LUAD were found and confirmed by analyzing RNA-seq data, in which mastermind-like transcriptional coactivator 2 (MAML2) was suppressed. The down-regulated genes whose expression was correlated to MAML2 expression were associated with patient prognosis. WGS analysis revealed somatic mutations associated with the H3K27ac marks in the MAML2 region and high levels of DNA methylation in MAML2 were observed in tumor samples. The second-level cluster analysis enabled patient stratification and subsequent analyses identified potential therapeutic target genes and treatment options. We overcome the persistent challenges of identifying alterations or driver mutations in coding regions related to tumorigenesis through a novel approach combining multi-omics data with clinical information to reveal the molecular mechanisms underlying non-CAGAs LUAD, stratify patients to improve patient prognosis, and identify potential therapeutic targets. This approach may be applicable to studies of other cancers with unmet needs.

Enhancing access to expensive oncology medications in Pakistan: The critical role of pharmaceutical patient assistance programs in oncology care.

This article aims to explore the access of patient assistance program (PAPs) and the role of pharmacists in improving access to oncology care in Pakistan. PAPs aim to reduce the financial burden of cancer in Pakistan, with pharmaceutical companies providing medication at reduced costs, ranging from 33% to 90%. Pharmacists play a pivotal role in managing these programs, facilitating PAP, pharmacist, oncology care setting, cancer therapy more accessible to those who faced financial barriers to accessing them.

Role of the lncRNA/Wnt signaling pathway in digestive system cancer: a literature review.

The long noncoding RNA (lncRNA)/Wingless (Wnt) axis is often dysregulated in digestive system tumors impacting critical cellular processes. Abnormal expression of specific Wnt-related lncRNAs such as LINC01606 (promotes motility), SLCO4A1-AS1 (promotes motility), and SH3BP5-AS1 (induces chemoresistance), plays a crucial role in these malignancies. These lncRNAs are promising targets for cancer diagnosis and therapy, offering new treatment perspectives. The lncRNAs, NEF and GASL1, differentially expressed in plasma show diagnostic potential for esophageal squamous cell carcinoma and gastric cancer, respectively. Additionally, Wnt pathway inhibitors like XAV-939 have demonstrated preclinical efficacy, underscoring their therapeutic potential. This review comprehensively analyzes the lncRNA/Wnt axis, highlighting its impact on cell proliferation, motility, and chemoresistance. By elucidating the complex molecular mechanisms of the lncRNA/Wnt axis, we aim to identify potential therapeutic targets for digestive system tumors to pave the way for the development of targeted treatment strategies.

Artificial Intelligence-Enhanced Risk Stratification of Cancer Therapeutics-Related Cardiac Dysfunction Using Electrocardiographic Images.

Background: Risk stratification strategies for cancer therapeutics-related cardiac dysfunction (CTRCD) rely on serial monitoring by specialized imaging, limiting their scalability. We aimed to examine an application of artificial intelligence (AI) to electrocardiographic (ECG) images as a surrogate for imaging risk biomarkers, and its association with early CTRCD. Methods: Across a U.S.-based health system (2013-2023), we identified 1,550 patients (age 60 [IQR:51-69] years, 1223 [78.9%] women) without cardiomyopathy who received anthracyclines and/or trastuzumab for breast cancer or non-Hodgkin lymphoma and had ECG performed ≤12 months before treatment. We deployed a validated AI model of left ventricular systolic dysfunction (LVSD) to baseline ECG images and defined low, intermediate, and high-risk groups based on AI-ECG LVSD probabilities of <0.01, 0.01 to 0.1, and ≥0.1 (positive screen), respectively. We explored the association with early CTRCD (new cardiomyopathy, heart failure, or left ventricular ejection fraction [LVEF]<50%), or LVEF<40%, up to 12 months post-treatment. In a mechanistic analysis, we assessed the association between global longitudinal strain (GLS) and AI-ECG LVSD probabilities in studies performed within 15 days of each other. Results: Among 1,550 patients without known cardiomyopathy (median follow-up: 14.1 [IQR:13.4-17.1] months), 83 (5.4%), 562 (36.3%) and 905 (58.4%) were classified as high, intermediate, and low risk by baseline AI-ECG. A high- vs low-risk AI-ECG screen (≥0.1 vs <0.01) was associated with a 3.4-fold and 13.5-fold higher incidence of CTRCD (adj.HR 3.35 [95%CI:2.25-4.99]) and LVEF<40% (adj.HR 13.52 [95%CI:5.06-36.10]), respectively. Post-hoc analyses supported longitudinal increases in AI-ECG probabilities within 6-to-12 months of a CTRCD event. Among 1,428 temporally-linked echocardiograms and ECGs, AI-ECG LVSD probabilities were associated with worse GLS (GLS -19% [IQR:-21 to -17%] for probabilities <0.1, to -15% [IQR:-15 to -9%] for ≥0.5 [p<0.001]). Conclusions: AI applied to baseline ECG images can stratify the risk of early CTRCD associated with anthracycline or trastuzumab exposure in the setting of breast cancer or non-Hodgkin lymphoma therapy.

Cell blebbing novel therapeutic possibilities to counter metastasis.

Cells constantly reshape there plasma membrane and cytoskeleton during physiological and pathological processes (Hagmann et al. in J Cell Biochem 73:488-499, 1999). Cell blebbing, the formation of bulges or protrusions on the cell membrane, is related to mechanical stress, changes in intracellular pressure, chemical signals, or genetic anomalies. These membrane bulges interfere with the force balance of actin filaments, microtubules, and intermediate filaments, the basic components of the cytoskeleton (Charras in J Microsc 231:466-478,2008). In the past, these blebs with circular structures were considered apoptotic markers (Blaser et al. in Dev Cell 11:613-627,2006). Cell blebbing activates phagocytes and promotes the rapid removal of intrinsic compartments. However, recent studies have revealed that blebbing is associated with dynamic cell reorganization and alters the movement of cells in-vivo and in-vitro (Charras and Paluch in Nat Rev Mol Cell Biol 9:730-736,2008). During tumor progression, blebbing promotes invasion of cancer cells into blood, and lymphatic vessels, facilitating tumor progression and metastasis (Weems et al. in Nature 615:517-525,2023). Blebbing is a dominant feature of tumor cells generally absent in normal cells. Restricting tumor blebbing reduces anoikis resistance (survival in suspension) (Weems et al. in Nature 615:517-525,2023). Hence, therapeutic intervention with targeting blebbing could be highly selective for proliferating pro-metastatic tumor cells, providing a novel therapeutic pathway for tumor metastasis with minimal side effects. Here, we review the association between cell blebbing and tumor cells, to uncover new research directions and strategies for metastatic cancer therapy. Finaly, we aim to identify the druggable targets of metastatic cancer in relation to cell blebbing.

BH3-mimetics or DNA-damaging agents in combination with RG7388 overcome p53 mutation-induced resistance to MDM2 inhibition.

The development of drug resistance reduces the efficacy of cancer therapy. Tumor cells can acquire resistance to MDM2 inhibitors, which are currently under clinical evaluation. We generated RG7388-resistant neuroblastoma cells, which became more proliferative and metabolically active and were less sensitive to DNA-damaging agents in vitro and in vivo, compared with wild-type cells. The resistance was associated with a mutation of the p53 protein (His193Arg). This mutation abated its transcriptional activity via destabilization of the tetrameric p53-DNA complex and was observed in many cancer types. Finally, we found that Cisplatin and various BH3-mimetics could enhance RG7388-mediated apoptosis in RG7388-resistant neuroblastoma cells, thereby partially overcoming resistance to MDM2 inhibition.

Innovative Fluorescent Polymers in Niosomal Carriers: A Novel Approach to Enhancing Cancer Therapy and Imaging.

Cancer is anticipated to become the pioneer reason of disease-related deaths worldwide in the next two decades, underscoring the urgent need for personalized and adaptive treatment strategies. These strategies are crucial due to the high variability in drug efficacy and the tendency of cancer cells to develop resistance. This study investigates the potential of theranostic nanotechnology using three innovative fluorescent polymers (FP-1, FP-2, and FP-3) encapsulated in niosomal carriers, combining therapy (chemotherapy and radiotherapy) with fluorescence imaging. These cargoes are assessed for their cytotoxic effects across three cancer cell lines (A549, MCF-7, and HOb), with further analysis to determine their capacity to augment the effects of radiotherapy using a Linear Accelerator (LINAC) at specific doses. Fluorescence microscopy is utilized to verify their uptake and localization in cancerous versus healthy cell lines. The results confirmed that these niosomal cargoes not only improved the antiproliferative effects of radiotherapy but also demonstrate the practical application of fluorescent polymers in in vitro imaging. This dual function underscores the importance of dose optimization to maximize therapeutic benefits while minimizing adverse effects, thereby enhancing the overall efficacy of cancer treatments.

The Cutting-edge of CRISPR for Cancer Treatment and its Future Prospects.

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a versatile technology that allows precise modification of genes. One of its most promising applications is in cancer treatment. By targeting and editing specific genes involved in cancer development and progression, CRISPR has the potential to become a powerful tool in the fight against cancer. This review aims to assess the recent progress in CRISPR technology for cancer research and to examine the obstacles and potential strategies to address them. The two most commonly used CRISPR systems for gene editing are CRISPR/Cas9 and CRISPR/Cas12a. CRISPR/Cas9 employs different repairing systems, including homologous recombination (HR) and nonhomologous end joining (NHEJ), to introduce precise modifications to the target genes. However, off-target effects and low editing efficiency are some of the main challenges associated with this technology. To overcome these issues, researchers are exploring new delivery methods and developing CRISPR/Cas systems with improved specificity. Moreover, there are ethical concerns surrounding using CRISPR in gene editing, including the potential for unintended consequences and the creation of genetically modified organisms. It is important to address these issues through rigorous testing and strict regulations. Despite these challenges, the potential benefits of CRISPR in cancer therapy cannot be overlooked. By introducing precise modifications to cancer cells, CRISPR could offer a targeted and effective treatment option for patients with different types of cancer. Further investigation and development of CRISPR technology are necessary to overcome the existing challenges and harness its full potential in cancer therapy.

Role of miRNA‑122 in cancer (Review).

MicroRNAs (miRNAs) are small non‑coding RNAs that serve key roles in cell proliferation, migration, invasion and apoptosis by regulating gene expression. In malignant tumors, miRNA‑122 serves either as a tumor suppressor or oncogene, influencing tumor progression via downstream gene targeting. However, the precise role of miRNA‑122 in cancer remains unclear. miRNA‑122 is a potential biomarker and modulator of radiotherapy and chemotherapy. The present review aimed to summarize the roles of miRNA‑122 in cancer, its potential as a biomarker for diagnosis and prognosis and its implications in cancer therapy, including radiotherapy and chemotherapy, alongside strategies for systemic delivery.

Carbon‐Based Biosensor in Point of Care Setting

AbstractIn medical diagnosis, detecting disease biomarkers at ultra‐low concentrations is vital. Point‐of‐care (POC) diagnostics require rapid detection, live monitoring, high sensitivity, low detection threshold, and cost‐effectiveness. Carbon‐based nanomaterials (CBNs) are promising due to their large surface‐to‐volume ratio, conductivity, biocompatibility, and stability, making them ideal for biosensors. Recent advancements in CBN applications, including biosensing, drug delivery, and cancer therapy, highlight their potential in enhancing detection sensitivity and specificity. Electrochemical sensors and biosensor platforms using carbon nanocomposites are pivotal in diagnostics. This review explores the current state and future challenges of CBN integration in POC settings, envisioning a transformative impact on healthcare diagnostics and therapeutics.

53719 Expert Guidance on the Prevention and Management of Dermatologic Adverse Events with Tumor Treating Fields (TTFields) Cancer Therapy in the Scalp and Thoracic Region

53719 Expert Guidance on the Prevention and Management of Dermatologic Adverse Events with Tumor Treating Fields (TTFields) Cancer Therapy in the Scalp and Thoracic Region

Polyester nanoparticles delivering chemotherapeutics: Learning from the past and looking to the future to enhance their clinical impact in tumor therapy.

Polymeric nanoparticles (NPs), specifically those comprised of biodegradable and biocompatible polyesters, have been heralded as a game-changing drug delivery platform. In fact, poly(α-hydroxy acids) such as polylactide (PLA), poly(lactide-co-glycolide) (PLGA), and poly(ε-caprolactone) (PCL) have been heavily researched in the past three decades as the material basis of polymeric NPs for drug delivery applications. As materials, these polymers have found success in resorbable sutures, biodegradable implants, and even monolithic, biodegradable platforms for sustained release of therapeutics (e.g., proteins and small molecules) and diagnostics. Few fields have gained more attention in drug delivery through polymeric NPs than cancer therapy. However, the clinical translational of polymeric nanomedicines for treating solid tumors has not been congruent with the fervor or funding in this particular field of research. Here, we attempt to provide a comprehensive snapshot of polyester NPs in the context of chemotherapeutic delivery. This includes a preliminary exploration of the polymeric nanomedicine in the cancer research space. We examine the various processes for producing polyester NPs, including methods for surface-functionalization, and related challenges. After a detailed overview of the multiple factors involved with the delivery of NPs to solid tumors, the crosstalk between particle design and interactions with biological systems is discussed. Finally, we report state-of-the-art approaches toward effective delivery of NPs to tumors, aiming at identifying new research areas and re-evaluating the reasons why some research avenues have underdelivered. We hope our effort will contribute to a better understanding of the gap to fill and delineate the future research work needed to bring polyester-based NPs closer to clinical application. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Elucidating the Role of Pro-renin Receptors in Pancreatic Ductal Adenocarcinoma Progression: A Novel Therapeutic Target in Cancer Therapy.

Pancreatic cancer is a highly aggressive malignancy with a very poor prognosis. The 5- year survival in these patients is very low, and most patients develop drug resistance to current therapies, so additional studies are needed to identify the potential role of new drug targets for the treatment of pancreatic cancer. Recent investigations have been performed regarding the roles of pro-renin receptors (PRR) in the initiation and development of cancers. PRR is a component of the local renin-angiotensin system (RAS). Local tissue RAS has been known in diverse organ systems, including the pancreas. Various investigations have implicated that PRRs are associated with the upregulation of various signaling pathways, like the renin-angiotensin system pathway, PI3K/Akt/mTOR, and the Wnt-signaling pathways, to contribute to pathological conditions, including cancer. In this review, we presented an overview of the role of PRR in the progression of pancreatic adenocarcinoma.

"One Method to Label Them All": A Single Fully Automated Protocol for GMP-Compliant 68Ga Radiolabeling of PSMA-11, Transposable to PSMA-I&T and PSMA-617.

Prostate-specific membrane antigen (PSMA) is an ideal target for molecular imaging and targeted radionuclide therapy in prostate cancer. Consequently, various PSMA ligands were developed. Some of these molecules are functionalized with a chelator that can host radiometals, such as 68Ga for PET imaging. The 68Ga radiolabeling step benefits from process automation, making it more robust and reducing radiation exposure. To design a single automated radiolabeling protocol for the GMP-compliant preparation of [68Ga]Ga-PSMA-11, transposable to the production of [68Ga]Ga-PSMA-617 and [68Ga]Ga-PSMA-I&T. A GAIA® synthesis module and a GALLIAD® generator were used. Radio-TLC and radio-HPLC methods were validated for radiochemical purity (RCP) determination. Three [68Ga]Ga-PSMA-11 validation batches were produced and thoroughly tested for appearance and pH, radionuclide identity and purity, RCP, stability, residual solvent and sterility. Minimal modifications were made to the reagents and disposables for optimal application to other PSMA ligands. [68Ga]Ga-PSMA-11 for clinical application was produced in 27 min. The 3 validation batches met the quality criteria expected by the European Pharmacopoeia to allow routine production. For optimal transposition to PSMA-617, the solid phase extraction cartridge was changed to improve purification of the radiolabeled product. For application to PSMA-I&T, the buffer solution initially used was replaced by HEPES 2.7 M to achieve good radiochemical yields. Residual HEPES content was checked in the final product and was below the Ph. Eur. threshold. A single automated radiolabeling method on the GAIA® module was developed and implemented for 68Ga radiolabeling of 3 PSMA ligands, with slight adjustments for each molecule.

In silico Identification of MHC Displayed Tumor Associated Peptides in Ovarian Cancer for Multi-Epitope Vaccine Construct.

Recognizing the potential of the immune system, immunotherapies have brought about a revolution in the treatment of cancer. Low tumour mutational burden and strong immunosuppression in the peritoneal tumor microenvironment (TME) lead to poor outcomes of immune checkpoint inhibition (ICI) and CART cell therapy in ovarian cancer. Alternative immunotherapeutic strategies are of utmost importance to achieve sound clinical success. The development of peptide vaccines based on tumor-associated antigens (TAAs) for ovarian cancer cells can be a potential target to provoke an anti-tumor immune response and subsequent clearance of tumour cells. The purpose of this in-silico study was to find potential epitopes for a multi-epitope vaccine construct using the immunopeptidomics landscape of ovarian carcinoma. The four TAAs (MUC16, IDO1, FOLR1, and DDX5) were selected as potential epitopes for B-cells, helper T-lymphocytes (HTLs), and cytotoxic T-lymphocytes (CTLs) predicted on the basis of antigenic, allergenic, and toxic properties. These epitopes were combined with suitable linkers and an adjuvant to form a multi-epitope construct. Four HTLs, 13 CTLs, and 6 potential B-cell epitopes were predicted from the TAAs. The designed multi-epitope construct was potentially immunogenic, non-toxic, and nonallergenic. Physicochemical properties and higher-order structural analyses of the final construct revealed a potential vaccine candidate. The designed vaccine construct has the potential to trigger both humoral and cellular immune responses and may be employed as a therapeutic immunization candidate for ovarian malignancies. However, further in vitro and animal experimentation is required to establish the efficacy of the vaccine candidate.

Ecological and evolutionary dynamics to design and improve ovarian cancer treatment.

Ovarian cancer ecosystems are exceedingly complex, consisting of a high heterogeneity of cancer cells. Development of drugs such as poly ADP-ribose polymerase (PARP) inhibitors, targeted therapies and immunotherapies offer more options for sequential or combined treatments. Nevertheless, mortality in metastatic ovarian cancer patients remains high because cancer cells consistently develop resistance to single and combination therapies, urging a need for treatment designs that target the evolvability of cancer cells. The evolutionary dynamics that lead to resistance emerge from the complex tumour microenvironment, the heterogeneous populations, and the individual cancer cell's plasticity. We propose that successful management of ovarian cancer requires consideration of the ecological and evolutionary dynamics of the disease. Here, we review current options and challenges in ovarian cancer treatment and discuss principles of tumour evolution. We conclude by proposing evolutionarily designed strategies for ovarian cancer, with the goal of integrating such principles with longitudinal, quantitative data to improve the treatment design and management of drug resistance. KEY POINTS/HIGHLIGHTS: Tumours are ecosystems in which cancer and non-cancer cells interact and evolve in complex and dynamic ways. Conventional therapies for ovarian cancer inevitably lead to the development of resistance because they fail to consider tumours' heterogeneity and cellular plasticity. Eco-evolutionarily designed therapies should consider cancer cell plasticity and patient-specific characteristics to improve clinical outcome and prevent relapse.

Analysis of neoadjuvant therapy effect on 30-day postoperative outcomes in gallbladder cancer

BackgroundThe role of neoadjuvant therapy (NAT) in gallbladder cancer (GBC) is not well established. We sought to evaluate the effect of NAT on postoperative outcomes following surgical resection of GBC. We hypothesized that patients receiving NAT would have similar rates of 30-day mortality, readmission, and postoperative complications (e.g. bile leakage and liver failure) compared to those who did not receive NAT. MethodsThe 2014–2017 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Procedure-Targeted Hepatectomy database was queried for patients that underwent surgery for GBC. Propensity scores were calculated to match patients in a 1:2 ratio based on age, comorbidities, functional status, and tumor staging. ResultsA total of 37 patients undergoing NAT were matched to 74 patients without NAT. There was no difference in any matched characteristics. Compared to the NAT group, the no NAT cohort had similar rates of postoperative bile leakage (NAT 13.5 % vs. no NAT 10.8 %, p = 0.31), postoperative liver failure (5.4 %, vs. 8.1 %, p = 0.60), 30-day readmission (10.8 % vs. 10.8 %, p = 1.00), and 30-day mortality (10.8 % vs. 2.7 %, p = 0.075). All 30-day complications were similar except for a higher rate of postoperative blood transfusion (NAT 32.4 % vs. no NAT 10.8 %, p = 0.005). ConclusionIn patients undergoing surgical resection for GBC, those with and without NAT had similar rates of readmission and 30-day mortality, however NAT was associated with an increased risk for transfusion. Despite use of a large national database, this study may be underpowered to adequately assess the effect of NAT on perioperative GBC outcomes and thus warrants further investigation.

A case of mixed neuroendocrine carcinoma–acinar adenocarcinoma: Utilization of triplet therapy for prostate cancer

IntroductionNeuroendocrine prostate cancer is an aggressive histological subtype of prostate cancer with a poor prognosis. Neuroendocrine prostate cancer is traditionally treated with cisplatin‐based chemotherapy, similar to that used in treating small‐cell lung cancer. However, the therapeutic effectiveness of chemotherapy for neuroendocrine prostate cancer has been limited. This case report describes a response to triplet therapy using darolutamide, androgen deprivation therapy, and docetaxel, which was administered in a patient with mixed neuroendocrine prostate cancer.Case presentationA 77‐year‐old man was newly diagnosed with mixed neuroendocrine prostate cancer. Serum prostate‐specific antigen, neuron‐specific enolase, and progastrin‐releasing peptide levels were 62.2, 40.6, and 60.6 pg/mL, respectively. Multiple lymph node metastases were identified on a computed tomography scan, and bone scintigraphy revealed multiple bone metastases. The clinical stage was determined to be cT3bN1M1b. Ultimately, tumor size and serum markers decreased with triplet therapy.ConclusionWe demonstrated the first case in which triplet therapy had been effective in the treatment of neuroendocrine prostate cancer.