Unraveling molecular characteristics and tumor microenvironment dynamics of neuroendocrine prostate cancer.

Prostate cancer (PCa) is the most prevalent malignancy and the second leading cause of cancer-related deaths among men. While adenocarcinoma of the prostate (adeno-PCa) is well-characterized, neuroendocrine prostate cancer (NEPC) remains poorly understood. Generally, NEPC is a rare but highly aggressive histological variant, however its limited patho-physiological understanding leads to insufficient treatment options associated with low survival rates for NEPC patients. Current treatments for NEPC, including platinum-based therapies, offer some efficacy, but there is a significant need for more targeted approaches. This review summarizes the molecular characteristics of NEPC in contrast to adeno-PCa, providing a comprehensive comparison. A significant portion of the discussion is dedicated to the tumor microenvironment (TME), which has recently been identified as a key factor in tumor progression. The TME includes various cells, signaling molecules, and the extracellular matrix surrounding the tumor, all of which play critical roles in cancer development and response to treatment. Understanding the TME's influence on NEPC could uncover new avenues for innovative treatment strategies, potentially improving outcomes for patients with this challenging variant of PCa.

Epigenetic regulation of p63 blocks squamous-to-neuroendocrine transdifferentiation in esophageal development and malignancy.

While cell fate determination and maintenance are important in establishing and preserving tissue identity and function during development, aberrant cell fate transition leads to cancer cell heterogeneity and resistance to treatment. Here, we report an unexpected role for the transcription factor p63 (Trp63/TP63) in the fate choice of the squamous versus neuroendocrine lineage in esophageal development and malignancy. Deletion of p63 results in extensive neuroendocrine differentiation in the developing mouse esophagus and esophageal progenitors derived from human embryonic stem cells. In human esophageal neuroendocrine carcinoma (eNEC) cells, p63 is transcriptionally silenced by EZH2-mediated H3K27 trimethylation (H3K27me3). Up-regulation of the major p63 isoform ΔNp63α, through either ectopic expression or EZH2 inhibition, promotes squamous transdifferentiation of eNEC cells. Together, these findings uncover p63 as a rheostat in coordinating the transition between squamous and neuroendocrine cell fates during esophageal development and tumor progression.

Unusual Presentation of Metastatic Medullary Thyroid Cancer Involving Bone Marrow, Kidneys, and Adrenal Gland: A Literature Review Based on a Case Report.

BACKGROUND: Medullary thyroid cancer (MTC) is one of the rare neuroendocrine malignancies. This cancer is hereditary in approximately 20% of cases. Although lymph node (LN) metastasis is prevalent in MTC, distant metastasis is not commonly seen in these patients. The most common locations for metastasis are the lungs, liver, and bones. This study presents an extremely rare MTC metastasis to bone marrow (BM) and adrenal gland, which has not been reported before. CASE: The patient was a 50-year-old man with a diagnosis of MTC and total thyroidectomy 2 months before his presentation. He came to the emergency department (ED) complaining of dyspnea, diffuse bone pain, nonbloody diarrhea, and abdominal cramps starting in the last month before. Initial treatment with intravenous fluid infusion and loperamide, due to the provisional diagnosis of infectious diarrhea, was ineffective. Further assessments revealed severe pancytopenia and a massive tumor above the left kidney. Bone marrow aspiration (BMA) and biopsy (BMB) led to the diagnosis of invasive metastasis of the MTC to the BM and the left adrenal gland. In the initial evaluations, his COVID-19 test became positive, and despite all efforts, his condition deteriorated, and he died 5 days after admission due to respiratory distress. CONCLUSION: Most MTC cases present with thyroid nodules in the initial steps and are confined to the thyroid gland or the adjacent LNs. These cases are mostly cured by thyroidectomy and LN dissection. This neuroendocrine cancer infrequently becomes aggressive and involves other parts of the body. However, involving BM or adrenal gland has been scarcely reported. Due to ineffective red and white blood cell production, BM metastasis can cause pancytopenia and, consequently, pallor, fatigue, dyspnea, and susceptibility to infections. High calcitonin levels can also cause diarrhea. The initial diagnosis is mostly with neck ultrasound (US) and fine needle aspiration (FNA). Total thyroidectomy is the main therapeutic option for these patients. Calcitonin and carcinoembryonic antigen (CEA) are sensitive indicators of recurrence or remaining tumors, which might be helpful for the initial diagnosis and postoperation follow-up. Although extremely rare, invasive metastasis of MTC might involve unusual body organs such as the BM or adrenal glands. In cases of unjustifiable pancytopenia or adrenal dysfunction in MTC-positive patients, these possibilities should be considered and ruled out by some specific evaluations, such as bone marrow biopsy and contrast-enhanced imaging.

Sporadic and Familial Medullary Thyroid Carcinoma: A Retrospective Single Center Study on Presentation and Outcome.

BACKGROUND: Medullary Thyroid Carcinoma (MTC) is a neuroendocrine tumor that arises from the thyroid C-cells. Most cases are sporadic (sMTC) while, approximately 25%, are hereditary (hMTC) due to germline mutations of REarranged during Transfection (RET) gene mutations and manifest in the framework of multiple endocrine neoplasia (MEN) 2A or 2B, or as pure familial MTC syndrome (FMTC). OBJECTIVE: The aim of this study is to evaluate the clinical, histopathological, biochemical and outcome differences between sMTC and hMTC. METHODS: Retrospective analysis of a consecutive series of 102 patients with histologically proven MTC diagnosed in the period between 2000 and 2022. For the analysis patients with MTC diagnosed during screening through genetic test were excluded. RESULTS: Patients with hMTC had higher incidence of multifocal and bilateral MTC and younger age at diagnosis. We did not found differences on tumor stage at diagnosis between sMTC and hMTC, such as time to progression and rate of persistent and recurrent disease. At univariate analysis, factors associated with persistent and recurrent disease during follow-up in patients with sMTC were tumor size, extrathyroidal extension, presence of lymph node metastases at diagnosis, pre- and post-operative calcitonin, post-operative CEA; in patients with hMTC, features associated with persistent and recurrent disease were lymph node metastases, post-operative calcitonin and pre- and post-operative CEA values. CONCLUSION: Patients with hMTC and sMTC had similar histopathological characteristics and clinical outcome.

Unveiling new chapters in medullary thyroid carcinoma therapy: advances in molecular genetics and targeted treatment strategies.

Medullary Thyroid Carcinoma (MTC), a neuroendocrine malignancy that arises from the calcitonin-secreting parafollicular C-cells of the thyroid, constitutes a minor yet impactful fraction of thyroid malignancies. Distinguished by its propensity for aggressive growth and a pronounced tendency for metastasis, MTC poses formidable obstacles to the early diagnosis and therapeutic intervention. The molecular genetics of MTC, particularly the role of the RET gene and the RAS gene family, have been extensively studied, offering insights into the pathogenesis of the disease and revealing potential therapeutic targets. This comprehensive review synthesizes the latest advancements in the molecular genetics of MTC, the evolution of precision therapies, and the identification of novel biomarkers. We also discuss the implications of these findings for clinical practice and the future direction of MTC research.

A Rare Case of Pulmonary Neuroendocrine Carcinoma in Transfusion-dependent Thalassemia Patient: Clinical Presentation, Management, and Implications.

Transfusion-dependent thalassemia (TDT) is often accompanied by complications related to iron overload and the development of malignant solid tumors or hematological malignancies. The occurrence of Neuroendocrine carcinoma, specifically in the respiratory tract, is very rare, with a prevalence of approximately 25%. Therefore, this study presented a case of a 42-year-old male with a beta-thalassemia major at 28 years, complaining of shortness of breath. This case was reported due to its rarity in providing information about solid tumors in thalassemia patients. The physical examination revealed several symptoms, including tachycardia, tachypnea, anemia, icteric sclera, elevated jugular venous pressure, coarse wet Ronchi in the medial to basal areas of both lungs, hepatomegaly, and splenomegaly (Schuffner 4). The patient regularly received blood transfusions and iron chelation therapy. A thoracic CT scan showed a lung mass and a biopsy of the mass revealed Pulmonary Neuroendocrine Carcinoma with high-grade proliferation and, large cell type. The patient also passed through cisplatin-etoposide chemotherapy for 6 cycles every 21 days. There is almost no data on pulmonary neuroendocrine carcinoma in thalassemia patients, so it is hoped that this case report can provide information about malignant solid tumors that can occur in thalassemia patients.

SNAP25-induced MYC upregulation promotes high-grade neuroendocrine lung carcinoma progression.

Background: This study investigated the expression and role of Synaptosome associated protein 25 (SNAP25) in high-grade neuroendocrine carcinoma (HGNEC). Methods: We used differentially expressed analysis and weighted gene co-expression network analysis (WGCNA) to identify key genes and modules in HGNEC. KEGG and GO analyses helped understand these genes' roles, and ROC curves assessed their diagnostic value. We also studied SNAP25's relation to immune infiltration and confirmed findings with in vitro and vivo experiments and datasets. Results: WGCNA identified 595 key genes related to pathways like MAPK signaling, GABAergic synapse, and cancer-related transcriptional misregulation. Top genes included SNAP25, MYC, NRXN1, GAD2, and SYT1. SNAP25 was notably associated with M2 macrophage infiltration. Dataset GSE40275 confirmed SNAP25's high expression and poor prognosis in HGNEC. qRT-PCR and WB analyses showed increased SNAP25 and c-MYC levels in HGNEC, promoting MEK/ERK pathway activity. Reducing SNAP25 decreased H1299 cell proliferation, migration, invasion, and levels of c-MYC, MEK, and ERK. Finally, in vivo experiments further confirmed that SNAP25 knockout can inhibit tumor growth. Conclusion: SNAP25 regulates c-MYC activation by stimulating the MEK/ERK pathway, ultimately influencing the development of HGNEC.

Comparison of proximal and distal gastric neuroendocrine carcinoma based on SEER database.

The occurrence of gastric neuroendocrine carcinoma (GNEC) is on the rise, and its prognosis is extremely poor. We compared survival outcomes between distal and proximal GNEC and developed a nomogram incorporating tumor site to enhance personalized management for patients with GNEC. 1807 patients were divided into DGNEC and PGNEC groups. We performed analyses by using propensity score matching (PSM) and Fine-Gray competing risk methods. A predictive nomogram for the prognosis of GNEC was constructed and validated. The cumulative incidence of cancer-specific death (CSD) in the DGNEC group was lower than that in the PGNEC group. Subgroup analysis showed lower CSD of DGNEC in males, females, tumor sizes (≤ 2 cm, 2 < tumor size ≤ 5 cm, > 5 cm, and unknown), grade stage I-II, and AJCC stage I-III, chemotherapy or no chemotherapy, surgery or no surgery groups (P < 0.05). Multivariate analysis revealed a significant association between PGNEC and CSD (HR, 1.4; 95% CI 1.13-1.73; P = 0.02). The independent predictors of CSD in patients with GNEC were primary site, gender, age, tumor size, AJCC stage, T stage, N stage, grade stage, and surgery. A predictive model based on multivariate analysis was constructed to estimate the probability of CSD at 1-, 3-, and 5-year. The calibration curves demonstrated excellent consistency between the predicted and observed probabilities of CSD. Patients with DGNEC have a better prognosis than those with PGNEC. The model exhibits strong predictive capability for these patients.

Comparison of insulinoma-associated protein 1 (INSM1) with traditional neuroendocrine markers in gastrointestinal and pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs).

The traditional diagnostic markers for mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are synaptophysin (SYP), chromogranin A (CHGA) and CD56. However, there is still a lack of a large series of article focused on the expression of insulinoma-associated protein 1 (INSM1) in gastrointestinal and pancreatic MiNENs. This study compared the expression of INSM1 and traditional neuroendocrine markers in MiNENs. In this study, we collected 46 cases of gastrointestinal and pancreatic MiNENs and performed immunohistochemical staining for INSM1, SYP, CHGA, and CD56. Histologically, the neuroendocrine components of MiNENs were all neuroendocrine carcinomas, with small cell neuroendocrine carcinomas accounting for 15.2% (7/46) and large cell neuroendocrine carcinomas accounting for 84.8% (39/46). With respect to immunohistochemical expression, the overall sensitivity of INSM1 was 80.4% (37/46), which was lower than that of SYP (100%, 46/46), but comparable to that of CHGA (67.4%, 31/46) or CD56 (73.9%, 34/46). The overall specificity of INSM1 was 91.3% (42/46), which was greater than that of SYP (63.0%, 29/46) and CD56 (69.6, 32/46), but was not significantly different from that of CHGA (82.6%, 38/46). The proportion of 3 + staining for SYP (100%, 46/46) was greater than that of INSM1 (71.7, 33/46), while the proportion of 3 + staining for CHGA (10.9, 5/46) or CD56 (21.7, 10/46) was lower than that of INSM1. In conclusion, INSM1 exhibited high sensitivity and specificity in the diagnosis of gastrointestinal and pancreatic MiNENs.

Immune checkpoint inhibitor therapy for primary neuroendocrine carcinoma of the gallbladder: A case report and literature review.

RATIONALE: Gallbladder neuroendocrine carcinoma (GNEC) is indeed a relatively rare malignant tumor of the gallbladder with neuroendocrine differentiation and the ability to produce and secrete a number of neurotransmitters and hormones, characteristics that make its clinical presentation and biological behavior likely to be different from those of other types of gallbladder cancer. Current treatment mostly relies on surgery and adjuvant chemotherapy and radiotherapy. PATIENT CONCERNS: We report a 53-year-old middle-aged male patient who underwent radical surgery for gallbladder malignancy after a diagnosis of neuroendocrine carcinoma of the gallbladder. DIAGNOSES: Diagnosis of neuroendocrine carcinoma of the gallbladder based on the return of pathologic findings. INTERVENTION: After local progression of postoperative chemotherapy with the first-line regimen of etoposide + cisplatin, an immune checkpoint inhibitor (traplizumab) + FOLIFIRI (fluorouracil + calcium folinate + irinotecan) regimen was used. OUTCOMES: The patient achieved 20 months of clinical survival and ultimately died of myelosuppression. LESSONS: The use of immune checkpoint inhibitors may become an effective tool in the treatment of neuroendocrine carcinoma of the gallbladder.

Clinical and pathological characteristics of gastric large cell neuroendocrine carcinoma: A report of 2 cases series and literature review.

RATIONALE: Gastric large cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive neuroendocrine carcinoma that arises from the stomach and with high malignancy. Patients with gastric LCNEC usually have a poor prognosis. The standard treatment plan has not been established and its curative effect is poor. The present study described 2 cases diagnosed with gastric LCNEC and reviewed in depth the literature to improve our understanding more about this uncommon tumor and further to provide more experience to diagnose and treat this disease. PATIENT CONCERNS: The present study reported 2 cases of gastric LCNEC in male patients aged 51 and 73 years old, respectively. Both patients had epigastric discomfort, pain, acid reflux and heartburn. The medical history was unremarkable. DIAGNOSES: The ulcerative lesion located at gastric was examined in the 2 patients by taking the esophagogastroduodenoscopy (EGO), computed tomography (CT) and digital gastrointestinal radiography (GI), that both were suspected gastric malignancy. Endoscopic biopsies of the tumor led to the initial diagnosis of gastric cancer. Postoperative pathological and immunohistochemical examinations of the surgical specimens confirmed that 1 case had mixed adeno-neuroendocrine carcinoma (MANEC) and the other had LCNEC. INTERVENTIONS: Both patients underwent surgical resection and received etoposide-cisplatin combination chemotherapy following surgery. OUTCOMES: The operation was successful. Both patients had uneventful recoveries following surgery, and had been followed-up regularly. The general condition was satisfactory, and no tumor metastasis was observed at present.

Variable Tracer Avidity and Interlesional Heterogeneity on 18 F-FDG, 68 Ga-DOTATATE, and 68 Ga-DOTA-FAPi-04 PET/CT Imaging in a Single Individual Patient With Progressive Metastatic Medullary Thyroid Carcinoma.

ABSTRACT: In medullary thyroid carcinoma (MTC), distant metastases have few therapeutic options with low success rates and substantial toxicity in many patients, warranting exploration of alternate systemic treatments with fewer adverse effects. The fibroblast activation protein inhibitor (FAPI)-based PET/CT opens new avenues for several cancers, including MTC. A case of MTC with varying tracer avidity and interlesional heterogeneity on 18 F-FDG, 68 Ga-DOTATATE, and 68 Ga-DOTA-FAPI-04 PET/CT imaging is presented. 68 Ga-DOTA-FAPI-04 PET/CT exhibited superior efficacy in terms of visualization of metastatic soft tissue, lymph nodal, and skeletal lesions, with enhanced target-to-background ratio compared with the other two, facilitating the detection of these lesions, thereby demonstrating the potential for theranostic translation.

Management of medullary thyroid cancer based on variation of carcinoembryonic antigen and calcitonin.

Carcinoembryonic antigen (CEA) and calcitonin (Ctn) are pivotal biomarkers in the diagnosis and management of medullary thyroid carcinoma (MTC). However, their diagnostic reliability in perioperative period remains a topic of ongoing debate. This review synthesizes researches on perioperative fluctuations in CEA and Ctn levels, and evaluates the impact of their different combinations on MTC diagnosis, treatment decisions, and prognosis. Our findings highlight it is crucial to understand and interpret the various combinations of CEA and Ctn fluctuations within a clinical context. Furthermore, to reduce diagnostic errors and improve patient outcomes, we recommend follow-up diagnostic and treatment protocols designed to address the potential pitfalls associated with the use of these biomarkers.

[Advances of Treatment of Pulmonary Large Cell Neuroendocrine Carcinoma].

Large cell neuroendocrine carcinoma (LCNEC) of lung is a rare neuroendocrine carcinoma subtype with difficulty in early diagnosis and poor prognosis which is treated with standard strategies of small cell lung cancer and non-small cell lung cancer. In recent years, the precise types of LCNEC and its response to therapy have been identified by next-generation sequencing. Some researches have also found the correlation between different subtypes of LCNEC and the efficacy of chemotherapy regimens. However, there is no consensual agreement of its therapy. Recently, immune checkpoint inhibitors (ICIs) has provided a new option for LCNEC patients based on some retrospective research data and case reports. In this review, we aimed to summarize the epidemiological characteristics, standard therapy, the advances of molecular subtypes and clinical applications of ICIs of LCNEC, so as to provide optimal systemic clinical decision-making for LCNEC patients.
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Revisiting ALK (D5F3) immunohistochemistry: Insights into focal staining and neuroendocrine differentiation.

BACKGROUND: Screening for anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC) is crucial for identifying patients eligible for targeted therapy. The FDA-approved ALK (D5F3) immunohistochemistry (IHC) assay, used with the OptiView Amplification Kit, demonstrates excellent sensitivity and specificity in detecting these patients. However, the clinical significance of resulting focal positivity remains unclear, and ALK (D5F3) expression unrelated to ALK fusion is observed in some cases of neuroendocrine differentiation. This study aims to validate these findings with molecular testing and contribute to the accurate interpretation of ALK (D5F3) IHC results. METHODS: A total of 1619 patients diagnosed with NSCLC and neuroendocrine carcinoma were evaluated using ALK (D5F3) IHC. For cases with strong but focal expression and those with diffuse strong positivity in neuroendocrine differentiation, ALK fluorescence in situ hybridization (FISH) and/or next-generation sequencing (NGS) tests were performed. RESULTS: Seven out of 1109 adenocarcinomas (0.6%) and six out of 289 squamous cell carcinomas (2.1%) exhibited strong focal ALK (D5F3) expression. Nine out of 209 neuroendocrine carcinomas (4.3%) showed homogeneously strong ALK (D5F3) expression. All these cases, including adenocarcinoma with neuroendocrine differentiation and combined small cell carcinoma, were negative for ALK fusions by FISH and/or NGS. CONCLUSION: This study demonstrates that strong but focal ALK (D5F3) immunostaining and strong expression in neuroendocrine differentiation may not indicate ALK fusion. By considering these findings, we can improve the accuracy of patient selection for targeted therapy by minimizing false-positive interpretations of ALK (D5F3) staining.

Large-cell neuroendocrine carcinoma of the bile duct: Case report of surgical treatment and adjuvant chemotherapy of 2 cases.

RATIONALE: Neuroendocrine carcinoma originating from extrahepatic bile duct is very rare, and only a few cases have been reported. Because of its scarcity of incidence, not much is known about the disease but for its aggressiveness and poor prognosis. PATIENT CONCERNS: In this report, we present 2 cases of large cell neuroendocrine carcinoma (LCNEC) originating from extrahepatic bile duct. Case 1: a 60-year-old woman presented with jaundice but no abdominal pain. Case 2: a 67-year-old man also presented with jaundice, along with abdominal discomfort and appetite loss. DIAGNOSES: Case 1: LCNEC with a focal adenocarcinoma component (pT2aN1M0, pStage IIIB). Case 2: LCNEC with a focal adenocarcinoma component (pT1N1M0, pStage IIB). INTERVENTIONS: Case 1: the patient underwent left hepatectomy and caudatectomy with hepaticojejunostomy, followed by 6 cycles of adjuvant chemotherapy (etoposide and cisplatin). Case 2: the patient underwent laparoscopic pylorus-preserving pancreatoduodenectomy, followed by 6 cycles of adjuvant chemotherapy (etoposide and cisplatin). OUTCOMES: Case 1: liver metastasis was detected 6 months postoperatively, and despite multiple chemotherapy regimens, the patient died 24 months post-surgery. Case 2: liver metastasis was detected 23 months postoperatively. The patient is still alive 36 months post-surgery after receiving multiple chemotherapy regimens and radiotherapy. LESSONS: Given the rarity of LCNEC, it is essential to continue collecting and reporting additional case studies to build a more comprehensive understanding of the disease. Although the prognosis for LCNEC is generally poor, the use of a multidisciplinary approach and further research will be critical in developing more effective treatment strategies in the future.

Thyroid Malignancy and Cutaneous Lichen Amyloidosis: Key Points Amid RET Pathogenic Variants in Medullary Thyroid Cancer/Multiple Endocrine Neoplasia Type 2 (MEN2).

We aimed to provide an updated narrative review with respect to the RET pathogenic variants and their implications at the clinical and molecular level in the diagnosis of medullary thyroid cancer (MTC)/multiple endocrine neoplasia (MEN) type 2, particularly with respect to the presence of cutaneous lichen amyloidosis (CLA). We searched English-language, in extenso original articles with no timeline nor study design restriction that were published on PubMed. A traditional interplay stands for CLA and MTC in MEN2 (not MEN3) confirmation. While the connection has been reported for more than three decades, there is still a large gap in understanding and addressing it. The majority of patients with MEN2A-CLA have RET pathogenic variants at codon 634; hence, it suggests an involvement of this specific cysteine residue in both disorders (most data agree that one-third of C634-positive subjects have CLA, but the ranges are between 9% and 50%). Females seem more prone to MEN2-CLA than males. Non-C634 germline RET pathogenic variants included (at a low level of statistical evidence) the following: RET V804M mutation in exon 14 for MTC-CLA (CLA at upper back); RET S891A mutation in exon 15 binding OSMR variant G513D (familial MTC and CLA comprising the lower legs to thighs, upper back, shoulders, arms, and forearms); and C611Y (CLA at interscapular region), respectively. Typically, CLA is detected at an early age (from childhood until young adulthood) before the actual MTC identification unless RET screening protocols are already applied. The time frame between CLA diagnosis and the identification of RET pathogenic variants was between 5 and 60 years according to one study. The same RET mutation in one family is not necessarily associated with the same CLA presentation. In MTC/MEN2 subjects, the most affected CLA area was the scapular region of the upper back. Alternatively, another hypothesis highlighted the fact that CLA is secondary to long-term prurit/notalgia paresthetica (NP) in MTC/MEN2. OSMR p. G513D may play a role in modifying the evolutionary processes of CLA in subjects co-harboring RET mutations (further studies are necessary to sustain this aspect). Awareness in CLA-positive patients is essential, including the decision of RET testing in selected cases.

The third symposium on treatment-induced neuroendocrine prostate cancer: insights and future directions.

Neuroendocrine prostate cancer (NEPC) is a rare and aggressive subtype of prostate cancer (PCa), emerging from advanced treatments and characterized by loss of androgen receptor (AR) signaling and neuroendocrine features, leading to rapid progression and treatment resistance. The third symposium on treatment-induced NEPC, held from 21 to 23 June 2024, at Harrison Hot Springs Resort, BC, Canada, united leading global researchers and clinicians. Sponsored by the Vancouver Prostate Centre (VPC), Canadian Institute of Health Research, Prostate Cancer Foundation Canada and Pharma Planter Inc, the event focused on the latest NEPC research and innovative treatment strategies. Co-chaired by Drs. Yuzhuo Wang and Martin Gleave, the symposium featured sessions on NEPC's historical context, molecular pathways, epigenetic regulation and the role of the tumor microenvironment and metabolism in its progression. Keynotes from experts like Dr. Himisha Beltran and Dr. Martin Gleave highlighted the complexity of NEPC. The Emerging Talent session showcased new research, pointing to the future of NEPC treatment. The symposium concluded with a consensus on the need for early detection, targeted therapies and personalized medicine to effectively combat NEPC, emphasizing the importance of global collaboration in advancing NEPC understanding and treatment.

CDHu40: a novel marker gene set of neuroendocrine prostate cancer.

Prostate cancer (PCa) is the most prevalent cancer affecting American men. Castration-resistant prostate cancer (CRPC) can emerge during hormone therapy for PCa, manifesting with elevated serum prostate-specific antigen levels, continued disease progression, and/or metastasis to the new sites, resulting in a poor prognosis. A subset of CRPC patients shows a neuroendocrine (NE) phenotype, signifying reduced or no reliance on androgen receptor signaling and a particularly unfavorable prognosis. In this study, we incorporated computational approaches based on both gene expression profiles and protein-protein interaction networks. We identified 500 potential marker genes, which are significantly enriched in cell cycle and neuronal processes. The top 40 candidates, collectively named CDHu40, demonstrated superior performance in distinguishing NE PCa (NEPC) and non-NEPC samples based on gene expression profiles. CDHu40 outperformed most of the other published marker sets, excelling particularly at the prognostic level. Notably, some marker genes in CDHu40, absent in the other marker sets, have been reported to be associated with NEPC in the literature, such as DDC, FOLH1, BEX1, MAST1, and CACNA1A. Importantly, elevated CDHu40 scores derived from our predictive model showed a robust correlation with unfavorable survival outcomes in patients, indicating the potential of the CDHu40 score as a promising indicator for predicting the survival prognosis of those patients with the NE phenotype. Motif enrichment analysis on the top candidates suggests that REST and E2F6 may serve as key regulators in the NEPC progression.

Bronchoscopic Interventional Therapy Combined With Pembrolizumab in the Treatment of Pulmonary Large Cell Neuroendocrine Carcinoma: A Case Report.

This study reports a significant clinical outcome following the use of bronchoscopic interventional therapy combined with pembrolizumab for treating pulmonary large cell neuroendocrine carcinoma (LCNEC), showcasing a novel approach in managing this aggressive cancer.