Outcomes of extensive stage extrapulmonary small cell cancer.

BACKGROUND: Extrapulmonary small cell cancer (EPSCC) is a rare malignancy with an incidence of approximately 0.1%-0.4% of all cancers. Treatment of this disease is often based on small cell lung cancer. AIMS: We aimed to investigate real-world clinical outcomes of patients with extensive-stage (ES) ESPCC. METHODS: Patients diagnosed with ES EPSCC between 2010 and 2020 from multiple centres in New South Wales were identified. Patient, disease and treatment characteristics were collected and presented using descriptive statistics. Survival was analysed using the Kaplan-Meier method. Univariate and multivariate Cox regression hazard models were used to identify potential prognostic factors. RESULTS: Sixty eligible ES EPSCC patients were identified, including 65% male and 35% female. The mean age was 69 years (range 37-88). Forty-five per cent were never smokers, 42% ex-smokers and 13% current smokers, and 17% of patients had limited-stage disease prior to development of ES disease. The most common primary sites were genitourinary (42%; mainly prostate (n = 14) and bladder (n = 10)), gastrointestinal (28%; mainly oesophagus (n = 5) and colon (n = 4)) and unknown primary (22%). Treatments received included palliative chemotherapy (67%), palliative radiotherapy (53%), palliative surgery (13%) and best supportive care alone (13%). The median overall survival (OS) was 8.0 months. The median progression-free survival was 5.4 months, and response rate to first-line chemotherapy was 65%. Platinum-based chemotherapy was prognostic of longer OS (HR 0.27, CI 0.12-0.60, P = 0.001). CONCLUSIONS: Patients with ES EPSCC had good response to palliative chemotherapy, but OS remained poor. Further research is required to improve the prognosis in this population.

Extrapulmonary Small Cell Cancer: A New Insight into a Rare Disease.

INTRODUCTION: Extrapulmonary small-cell cancer (EPSCC) is a relatively rare malignancy. The management of EPSCC is usually extrapolated from small-cell lung cancer (SCLC). In spite of the morphological similarity of the 2 malignancies, there are many differences in clinical features, prognosis, and recommendations of treatment of these disorders. The data on the correlation of clinical-pathological characteristics of EPSCC and treatment results is scarce. MATERIALS AND METHODS: This retrospective analysis of 41 consecutively treated patients diagnosed with EPSCC in 2015-2018 was performed in a tertiary medical center. The correlation between the clinical and pathological characteristics and the treatment outcome (response rate, disease-free interval, and overall medial survival) was done using the standard statistics, Kaplan-Meier method, and multivariate analyses. The stratification was done on the stage of the disease, Ki-67 proliferative index, the location of the tumor, and smoking. RESULTS: Forty-one patients were included with a median age of 66.3 years. The most common primary site was the gastrointestinal tract (28, 68.3%) including the pancreas. The most common distant metastasis site was the liver (23, 56.1%). Only 2 patients (4.9%) had brain metastases. Unlike in SCLC, most patients did not have any history of smoking (23, 56.1%). Nineteen patients with metastatic disease received systemic treatment, mostly cisplatin-based chemotherapy, with a response rate of 57.9%. The results of treatment were significantly better in patients with disseminated EPSCC with Ki-67 <55%, while its role in limited disease was nonsignificant. DISCUSSION: The results of our study show the unique entity of EPSCC. The rarity of brain metastases proves that prophylactic brain irradiation should not be recommended in practice. The provocative idea of prophylactic liver irradiation in limited-stage EPSCC of gastrointestinal origin can be evaluated in future studies. The predictive role of Ki-67 is important in metastatic EPSCC. There is probably no role of smoking in developing EPSCC.

Association of Systemic Steroid Treatment and Outcome in Patients Treated with Immune Checkpoint Inhibitors: A Real-World Analysis.

BACKGROUND: Immune-related adverse events (irAEs) are inflammatory side effects, which can occur during immune-checkpoint(s) inhibitors (ICIs) therapy. Steroids are the first-line agents to manage irAEs because of their immunosuppressive properties. However, it is still debated whether or when steroids can be administered without abrogating the therapeutic efforts of immunotherapy. METHODS: We retrospectively evaluated 146 patients with metastatic non-small cell lung cancer (NSCLC), melanoma and renal cell carcinoma (RCC) treated with ICIs. We assessed the progression-free survival (PFS) of patients treated with steroids due to an irAE compared to a no-steroid group. RESULTS: The early treatment with steroid (within the first 30 days from the beginning of immunotherapy) was not related to a shorter PFS (p = 0.077). Interestingly, patients who were treated with steroids after 30 days from the start of immunotherapy had significantly longer PFS (p = 0.017). In a multivariate analysis, treatment with steroids after 30 days was an independent prognostic factor for PFS (HR: 0.59 [95% CI 0.36-0.97], p = 0.037). CONCLUSIONS: This retrospective study points out that early systemic steroids administration to manage irAEs might not have a detrimental effect on patient clinical outcome in NSCLC, melanoma and RCC patients.

[Surgery treatment and prognosis analysis of 129 small cell carcinoma of the esophagogastric junction].

Objective: To analysis the prognosis related factors of patients with small cell cancer of the esophagogastric junction treated by surgery. Methods: The clinicopathologic data of 129 patients with small cell cancer of the esophagogastric junction underwent surgery treatment in the Fourth Hospital of Hebei Medical University from January 2004 to December 2010 were retrospectively analyzed. Univariate survival survival was performed by Kaplan-Meier method and Log rank test. Multivariate survival was analyzed by using Cox proportional hazard model. Results: Radical surgery was performed in 123 patients, whereas other 6 cases were conducted palliative operation. The 5-year overall survival (OS) rate of this cohort was 21.0% and median survival time was 25.7 months. The 5-year progression free survival (PFS) rate of this cohort was 11.0% and median PFS time was 19.1 months. The univariate analysis result showed that operation manner, radical or not, tumor length, lymph node metastasis, TNM stage, intravascular cancer embolus surgical margin positive or not, the expression of Syn, comprehensive treatment and radiochemotherapy after progression were associated with the OS of these patients (P<0.05). Multivariate analysis result showed that lymph node metastasis, radiochemotherapy after progression were independent risk factors of OS (P<0.05). Univariate analysis result showed that operation manner, radical or not, tumor length, TNM stage, lymph node metastasis, intravascular cancer embolus, surgical margin positive or not, the expression of Syn, comprehensive treatment and radiochemotherapy after progression were associated with PFS (P<0.05). Multivariate analysis showed that lymph node metastasis and radiochemotherapy after progression were independent risk factors of PFS (P<0.05). Conclusions: The prognosis of small cell cancer of the esophagogastric junction patients remains poor. Lymph node metastasis and radiochemotherapy after progression are regarded as independent prognostic factors of these patients.

Neuroendocrine carcinoma of the cervix: a systematic review of the literature.

BACKGROUND: Neuroendocrine carcinoma of the cervix (NECC) is a rare variant of cervical cancer. The prognosis of women with NECC is poor and there is no standardized therapy for this type of malignancy based on controlled trials. METHODS: We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify clinical trials describing the management and outcome of women with NECC. RESULTS: Three thousand five hundred thirty-eight cases of NECC in 112 studies were identified. The pooled proportion of NECC among women with cervical cancer was 2303/163470 (1.41%). Small cell NECC, large cell NECC, and other histological subtypes were identified in 80.4, 12.0, and 7.6% of cases, respectively. Early and late stage disease presentation were evenly distributed with 1463 (50.6%) and 1428 (49.4%) cases, respectively. Tumors expressed synaptophysin (424/538 cases; 79%), neuron-specific enolase (196/285 cases; 69%), chromogranin (323/486 cases; 66%), and CD56 (162/267; 61%). The most common primary treatment was radical surgery combined with chemotherapy either as neoadjuvant or adjuvant chemotherapy, described in 42/48 studies. Radiotherapy-based primary treatment schemes in the form of radiotherapy, radiochemotherapy, or radiotherapy with concomitant or followed by chemotherapy were also commonly used (15/48 studies). There is no standard chemotherapy regimen for NECC, but cisplatin/carboplatin and etoposide (EP) was the most commonly used treatment scheme (24/40 studies). Overall, the prognosis of women with NECC was poor with a mean recurrence-free survival of 16 months and a mean overall survival of 40 months. Immune checkpoint inhibitors and targeted agents were reported as being active in three case reports. CONCLUSION: NECC is a rare variant of cervical cancer with a poor prognosis. Multimodality treatment with radical surgery and neoadjuvant/adjuvant chemotherapy with cisplatin and etoposide with or without radiotherapy is the mainstay of treatment for early stage disease while chemotherapy with cisplatin and etoposide or topotecan, paclitaxel, and bevacizumab is appropriate for women with locally advanced or recurrent NECC. Immune checkpoint inhibitors may be beneficial, but controlled evidence for their efficacy is lacking.

3D carbon nanosphere and gold nanoparticle-based voltammetric cytosensor for cell line A549 and for early diagnosis of non-small cell lung cancer cells.

An electrochemical cytosensor for the detection of the non-small-cell lung cancer cell line A549 (NSCLC) had been developed. A microwave-hydrothermal method was employed to prepare monodisperse colloidal carbon nanospheres (CNSs). Gold nanoparticles (AuNPs) were placed on the surface of the colloidal CNSs by self-assembly to obtain 3D-structured microspheres of the type CNS@AuNP. The results of an MTT assay show the microspheres to possess good biocompatibility. The CNS@AuNP nanocomposite was then placed, in a chitosan film, on a glassy carbon electrode (GCE). The voltammetric signals and detection sensitivity are significantly enhanced owing to the synergistic effect of CNSs and AuNPs. A cytosensor was then obtained by immobilization of antibody against the carcinoembryonic antigen (which is a biomarker for NSCLC) on the GCE via crosslinking with glutaraldehyde. Hexacyanoferrate is used as an electrochemical probe, and the typical working voltage is 0.2 V (vs. SCE). If exposed to A549 cells, the differential pulse voltammetric signal decreases in the 4.2 × 10-1 to 4.2 × 10-6 cells mL-1 concentration range, and the detection limit is 14 cells mL-1 (at S/N = 3). Graphical abstract Schematic presentation of design strategy and fabrication process of the electrochemical cytosensor for A549 cells. (CNS: carbon nanospheres; GA: glutaraldehyde; PEI: polyethyleneimine; AuNPs: gold nanoparticles; BSA: Bovine serum albumin).

Prognostic significance of serum neuron-specific enolase in small cell carcinoma of the urinary bladder.

PURPOSE: Small cell carcinoma of the urinary bladder (SCCB) is known for its aggressive clinical features and poor prognosis. No prognostic factor has been established so far. The aim of this study was to assess the significance of possible prognostic factors, including serum neuron-specific enolase (NSE), an established biomarker for small cell lung carcinoma. METHODS: We retrospectively reviewed 31 patients with primary SCCB treated at our eight affiliate institutions between 2001 and 2014. The association of various clinicopathological factors at diagnosis, including the serum NSE value, with cancer-specific survival (CSS) was assessed. The log-rank test and Cox proportional hazards model were used for univariate and multivariate analyses, respectively. RESULTS: Nineteen (61.3 %) died of SCCB during the follow-up, with a median survival time of 12.7 months. Prognostic factors were analyzed for the 25 patients after excluding six with missing data. Univariate analysis demonstrated that stage (extensive disease) and serum NSE ≥25 ng/ml were significantly associated with worse CSS. Multivariate analysis identified increased serum NSE value as a sole independent predictor of CSS (hazard ratio 18.52, p = 0.0022). CONCLUSIONS: Serum NSE value at diagnosis was an independent prognostic factor for primary SCCB and may serve as a useful biomarker in the management of SCCB.

Proteome screening of pleural effusions identifies IL1A as a diagnostic biomarker for non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a common malignant disease, and in ~10-20% of patients, pleural effusion is the first symptom. The pleural effusion proteome contains information on pulmonary disease that directly or indirectly reflects pathophysiological status. However, the proteome of pleural effusion in NSCLC patients is not well understood, nor is the variability in protein composition between malignant and benign pleural effusions. Here, we investigated the different proteins in pleural effusions from NSCLC and tuberculosis (TB) patients by using nano-scale liquid chromatography-tandem mass spectrometry (nLC-MS/MS) analysis. In total, 363 proteins were identified in the NSCLC pleural effusion proteome with a low false discovery rate (<1%), and 199 proteins were unique to NSCLC. The proteins in the NSCLC patients' pleural effusion were involved in cell adhesion, proteolysis, and cell migration. Furthermore, interleukin 1 alpha (IL1A), a protein that regulates tumor growth, angiogenesis, and metastasis, was significantly more abundant in the NSCLC group compared to the TB group, a finding that was validated with an ELISA assay.

Synchronous primary cancers of trachea and esophagus and ventricular tachycardia.

The incidence of multiple primary cancers involving trachea is rare. We present a case of synchronous double primary cancer of trachea and esophagus in a 70-year-old woman, with a special symptom of ventricular tachycardia and no history of smoking and alcohol drinking. Biopsies from multiple foci demonstrated the patient had primary small cell cancer of trachea and squamous cell carcinoma in situ of esophagus. The patient was successfully treated with four cycles of chemotherapy consisting of etoposide and carboplatin (EC) followed by thoracic radiotherapy (60 Gy in 30 fractions, in 6 weeks), and was evaluated to have complete response of tumor. To our knowledge, there is no synchronous cancer of trachea and esophagus has been reported in English literature, and our experience showed sequential EC chemotherapy and radiotherapy provided an effective treatment to control both cancers.

CT-based different regions of interest radiomics analysis for acute radiation pneumonitis in patients with locally advanced NSCLC after chemoradiotherapy.

Purpose: To establish a radiomics model using radiomics features from different region of interests (ROI) based on dosimetry-related regions in enhanced computed tomography (CT) simulated images to predict radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC). Methods: Our retrospective study was conducted based on a cohort of 236 NSCLC patients (59 of them with RP≥2) who were treated in 2 institutions and divided into the primary cohort (n = 182,46 of them with RP≥2) and external validation cohort (n = 54,13 of them with RP≥2). Radiomic features extracted from three ROIs were defined as the whole lung (WL), the dose volume histogram (DVH) of the lung V20 (V20_Lung) and the DVH of the V30 of lung minus the planning target volume (PTV) (V30 Lung-PTV). A total of 107 radiomics features were extracted from each ROIs. The U test, correlation coefficient and least absolute shrinkage and selection operator (LASSO) were performed for features selection. Six models based on different classification algorithms were developed to select the best radiomics model (R model).In addition, we built a dosimetry model then combined it with the best R model to create a mixed model (R+D model) The receiver operating characteristic (ROC) curve was delineated to assess the predictive efficacy of the models. Decision curve analysis could benefit from the model proposals through the assessment of clinical utility. Results: Among the three ROIs, the best R model constructed from the LightGBM algorithm demonstrated the strongest discriminative ability in the ROI of V30 Lung-PTV. The corresponding area under the curve (AUC) value was 0.930 (95 % confidence interval (CI): 0.829-0.941). The D model, R model and R+D model achieved AUC values of 0.798 (95 %CI: 0.732-0.865), 0.930 (95 %CI: 0.829-0.941) and 0.940 (95 %CI: 0.906-0.974) in primary cohort, and in external validation cohort, the AUC values were 0.793 (95 %CI:0.637-0.949), 0.887 (95 %CI:0.810-0.993), 0.951 (95CI%:0.891-1.000). Decision curve demonstrate that R+D model could benefit for patients through the assessment of clinical utility. Conclusion: The radiomics model was able to predict the acute RP more effectively in comparison with the traditional dosimetry model. Especially the radiomics model based on the V30 Lung-PTV region was able to achieve a higher accuracy when compared to the other regions.

Small cell carcinoma with neuroendocrine differentiation of subglottic larynx- a case report.

Small cell cancer (SCC) is a neuroendocrine neoplasm, which is most frequently found in the lungs. Extrapulmonary location of SCC is rare and may involve 2.5-5% of SCCs. We present a case of a 31-year-old male patient with an extremely uncommon subglottic SCC. The patient was qualified for a radical sequential chemoradiotherapy. After treatment, patient's condition suggested complete remission. Recurrence was detected one year later, and the disease rapidly progressed, despite a second line chemotherapy. The patient died 29 months after initial diagnosis. This case aims to raise awareness on the aggressive laryngeal SCC and its good response to first line chemotherapy composed of cisplatin and etoposide, followed by radiotherapy.

Small-cell cancer of the perihilar bile duct with bleeding esophageal varices: A report of a rare case.

Small-cell cancer is an uncommon histological subtype of neuroendocrine carcinoma. It frequently has a poor prognosis because of distant metastasis. It is diagnosed using histopathological and immunohistochemical tests. We report the case of a 29-year-old female with small-cell cancer in the perihilar bile duct who presented with bleeding esophageal varices. This case report aims to improve physicians' understanding of small-cell cancer, thereby helping to reduce the frequency of missed clinical diagnoses.

Metastasis from small cell lung cancer to ovary: A case report.

Small cell lung cancer (SCLC) rarely metastasizes to the ovary, and is difficult to diagnose given its overlapping clinical features and histological characteristics with primary ovarian cancer. Since therapies for SCLC and primary ovarian cancer differ, it is important to determine the original site of ovarian lesions. This report describes the differential diagnosis of metastatic from primary ovarian cancer. A 46-year-old Chinese woman with a history of SCLC, confirmed by transbronchial lung biopsy in August 2018, presented with abdominal distension in December 2018. Ultrasound examination and whole abdomen computed tomography showed one mass in each ovary. A provisional diagnosis of ovarian tumor was given. A palliative total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed; and three postoperative courses of chemotherapies. The patient died from multiple organ failure in May 2019. Metastatic ovarian cancer from SCLC was determined based on characteristic histological and immunohistochemical staining.

Neoadjuvant SBRT combined with immunotherapy in NSCLC: from mechanisms to therapy.

The utilisation of neoadjuvant immunotherapy has demonstrated promising preliminary clinical outcomes for early-stage resectable non-small-cell lung cancer (NSCLC). Nevertheless, it is imperative to develop novel neoadjuvant combination therapy regimens incorporating immunotherapy to further enhance the proportion of patients who derive benefit. Recent studies have revealed that stereotactic body radiotherapy (SBRT) not only induces direct tumour cell death but also stimulates local and systemic antitumour immune responses. Numerous clinical trials have incorporated SBRT into immunotherapy for advanced NSCLC, revealing that this combination therapy effectively inhibits local tumour growth while simultaneously activating systemic antitumour immune responses. Consequently, the integration of SBRT with neoadjuvant immunotherapy has emerged as a promising strategy for treating resectable NSCLC, as it can enhance the systemic immune response to eradicate micrometastases and recurrent foci post-resection. This review aims to elucidate the potential mechanism of combination of SBRT and immunotherapy followed by surgery and identify optimal clinical treatment strategies. Initially, we delineate the interplay between SBRT and the local tumour immune microenvironment, as well as the systemic antitumour immune response. We subsequently introduce the preclinical foundation and preliminary clinical trials of neoadjuvant SBRT combined with immunotherapy for treating resectable NSCLC. Finally, we discussed the optimal dosage, schedule, and biomarkers for neoadjuvant combination therapy in its clinical application. In conclusion, the elucidation of potential mechanism of neoadjuvant SBRT combined immunotherapy not only offers a theoretical basis for ongoing clinical trials but also contributes to determining the most efficacious therapy scheme for future clinical application.

Case Report: Unveiling an Incidentally Diagnosed Extrapulmonary Small Cell Carcinoma of the Rectum.

Extrapulmonary small cell carcinoma (EPSCC) is a rare malignancy with distinct clinical and pathological characteristics. We present the case of a 72-year-old male diagnosed with EPSCC of the rectum during a routine screening colonoscopy. The patient was asymptomatic, and pathological examination revealed a rectal mass displaying features of small cell carcinoma (SCC) associated with tubular adenoma. The treatment comprised radiation therapy and cisplatin/etoposide chemotherapy. This case underscores the importance of considering EPSCC as a potential diagnosis in patients with rectal masses, necessitating further studies to optimize treatment strategies.

Oligoprogression in non-small cell lung cancer: a narrative review.

Background and Objective: Non-small cell lung cancer (NSCLC) accounts for 80% of lung cancers and is the most common non-cutaneous cancer world-wide. In NSCLC, oligometastatic and oligoprogressive disease (OPD) have been recognized as separate entities within the realm of metastatic disease and are emerging concepts in the context of targeted systemic therapies. Our objectives are to discuss the current literature regarding the evolving definitions of OPD in the context of oligometastatic disease (OMD) for NSCLC. Further, to discuss current and future clinical trials that have shaped our local approach with stereotactic body radiation therapy (SBRT)/stereotactic ablative radiotherapy (SABR). Methods: Literature on OPD in NSCLC and local ablative therapy (LAT) including SBRT/SABR and stereotactic radiosurgery (SRS) was reviewed. Key Content and Findings: Oligoprogression is defined as limited (usually 3-5) metastatic areas progressing while on/off systemic therapy in the background of oligometastatic or polymetastatic disease. Prognosis in OPD with treatment (such as LAT and systemic therapy) may be more favorable. Outcomes for patients progressing on tyrosine kinase inhibitors (TKIs) with molecular mutations [such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK)] who receive LAT are promising. Conclusions: Patients presenting with NSCLC metastasis with progression at a limited number of sites on/off a given line of systemic therapy may have favorable outcomes with aggressive LAT, which includes SBRT/SABR/SRS. Further studies need to be completed to further optimize treatment recommendations.

Mixed endocervical adenocarcinoma and high-grade neuroendocrine carcinoma of the cervix: A case report.

Adenocarcinoma admixed with neuroendocrine carcinoma of the uterine cervix is a rare malignancy with a poor prognosis. In the literature, there are few reported cases. Herein, we report a case of a 56-year-old Turkish woman with cervical adenocarcinoma admixed with small cell neuroendocrine carcinoma. Histological examination of endocervical curettage specimens revealed a tumor composed of almost equal areas of small cell neuroendocrine carcinoma and adenocarcinoma. Neuroendocrine differentiation was confirmed by immunohistochemistry for chromogranin-A, synaptophysin, and CD 56. After the adenocarcinoma and small cell neuroendocrine carcinoma association was detected in the curettage material, both cervicovaginal smear and then total abdominal hysterectomy and bilateral salpingo-oophorectomy resection material of the patient were submitted to our pathology department. Histological features of both curettage and resection material were determined by immunohistochemical studies.

Mediastinal small cell carcinoma with a metastasis to the orbit: A rare carcinoma with an unusual metastatic progression.

Extraocular muscle (EOM) is a rare site for orbital metastasis. We presented a case of solitary EOM metastasis from mediastinal small cell cancer (MSCC) for the first time. A 49-year-old man presented with hoarseness. Thorax computed tomography (CT) revealed a mediastinal mass. A fine-needle aspiration biopsy (FNAB) confirmed the diagnosis of MSCC. The patient staged as limited-stage MSCC with a positron emission computed tomography (PET-CT). The patient received radical chemo-radiotherapy (CRT). PET-CT showed a complete response after CRT. Afterward, the patient presented with double vision and a headache. Brain magnetic resonance imaging (MRI) demonstrated a 2 cm metastatic lesion at the left inferior rectus muscle. A 30 Gy palliative RT was applied. The full regression of the mass was achieved 3 months after the palliative RT. Although solitary EOM metastasis is rare, the timing of accurate diagnosis and appropriate treatment can help to preserve the patient's vision and relieve complaints related to the mass.

Primary Esophageal Small Cell Carcinoma Masquerading as Non-Hodgkin Lymphoma in a Young Patient.

BACKGROUND/AIM: Small cell cancer of the esophagus (SCCE) is an extremely rare entity with an aggressive clinical course, thus early diagnosis and treatment are important for improved survival. CASE REPORT: A 35-year-old male presented with dysphagia, loss of appetite and weight loss. Diagnostic workup revealed an esophageal mass, which was diagnosed as primary non-Hodgkin lymphoma (NHL) on initial biopsy. Despite receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy for 3 months, there was an interval increase in the size of the esophagus mass, which unveiled underlying SCCE. A re-review of the previous biopsy specimen with immunohistochemical staining confirmed the initial diagnosis as SCCE as well. Despite 4 cycles of platinum-based chemotherapy and radiotherapy, the malignancy progressed and proved fatal. CONCLUSION: SCCE and non-Hodgkin lymphomas are rare entities, whose morphologies can be diagnostically challenging, hence they require special immunostaining for accurate diagnosis. Prompt diagnosis and initiation of treatment can confer better quality of life and survival.

Discovery of a novel CDK7 inhibitor YPN-005 in small cell lung cancer.

In contrast to non-small cell lung cancer, there has been no significant progress in the development of therapies for the small cell lung cancer (SCLC) in recent decades. Although various targeted agents, including immunotherapies, have recently been developed for testing in clinical trials, novel therapeutic agents are still needed for SCLC. We developed a potent inhibitor of cyclin-dependent kinase 7 (CDK7), designated YPN-005, and sought to determine whether it showed any anticancer effects in SCLC cells, cisplatin or etoposide-resistant cells, or organoids derived from SCLC patients. In a panel of kinases assay, YPN-005 was highly selective for CDK7 and showed antiproliferative effects in SCLC and cells with acquired resistance to conventional anticancer drugs. Similar to other CDK7 inhibitors, YPN-005 treatment significantly decreased the phosphorylation of the carboxyl-terminal domain of RNA polymerase II. Consistent with the in vitro results, YPN-005 treatment showed a significant inhibition of tumor growth through the suppression of RNA polymerase II phosphorylation. Finally, YPN-005 showed potent anticancer effects in organoids derived from SCLC patients compared to another CDK7 inhibitor, THZ1. Therapeutic targeting of CDK7 in SCLC might be suitable for clinical investigation, and YPN-005 may be a promising therapeutic option for primary SCLC and SCLC with acquired resistance to conventional therapy.