Simple Summary Our study centers on refining the diagnosis of small-cell lung cancer (SCLC), a unique subtype with distinct therapeutic implications compared to other lung cancers. Our primary goal is the identification of specific differentially expressed proteins in SCLC as opposed to healthy lung tissue. Additionally, we aim to discern the protein expression of SCLC from large cell neuroendocrine carcinoma (LCNEC), a closely related entity. This research has the potential to enhance our understanding of these intricate lung cancers, potentially transforming the landscape of detection and tailored treatment strategies. Abstract The accurate diagnosis of small-cell lung cancer (SCLC) is crucial, as treatment strategies differ from those of other lung cancers. This systematic review aims to identify proteins differentially expressed in SCLC compared to normal lung tissue, evaluating their potential utility in diagnosing and prognosing the disease. Additionally, the study identifies proteins differentially expressed between SCLC and large cell neuroendocrine carcinoma (LCNEC), aiming to discover biomarkers distinguishing between these two subtypes of neuroendocrine lung cancers. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search was conducted across PubMed/MEDLINE, Scopus, Embase, and Web of Science databases. Studies reporting proteomics information and confirming SCLC and/or LCNEC through histopathological and/or cytopathological examination were included, while review articles, non-original articles, and studies based on animal samples or cell lines were excluded. The initial search yielded 1705 articles, and after deduplication and screening, 16 articles were deemed eligible. These studies revealed 117 unique proteins significantly differentially expressed in SCLC compared to normal lung tissue, along with 37 unique proteins differentially expressed between SCLC and LCNEC. In conclusion, this review highlights the potential of proteomics technology in identifying novel biomarkers for diagnosing SCLC, predicting its prognosis, and distinguishing it from LCNEC.

Simple Summary Merkel cell carcinoma (MCC) is a rare and highly aggressive type of skin neuroendocrine cancer that frequently recurs and metastasizes within a relatively short period. Despite rapid growth and characteristic skin color, MCC often goes undiagnosed in its early stage. Therefore, therapy is often initiated at the advanced stage, and selecting appropriate therapeutic interventions is critical. The emergence of novel immunotherapeutic agents, such as immune checkpoint inhibitors (ICI), presents a promising treatment option for advanced MCC. Several biomarkers, such as PD-L1 expression, tumor mutational burden (TMB), and microsatellite instability (MSI), showed significant potential as predictive biomarkers for treatment with ICI. Despite their predictive value, each has demonstrated limited value in MCC over recent years. Abstract Merkel cell carcinoma (MCC) is primarily a disease of the elderly Caucasian, with most cases occurring in individuals over 50. Immune checkpoint inhibitors (ICI) treatment has shown promising results in MCC patients. Although ~34% of MCC patients are expected to exhibit at least one of the predictive biomarkers (PD-L1, high tumor mutational burden/TMB-H/, and microsatellite instability), their clinical significance in MCC is not fully understood. PD-L1 expression has been variably described in MCC, but its predictive value has not been established yet. Our literature survey indicates conflicting results regarding the predictive value of TMB in ICI therapy for MCC. Avelumab therapy has shown promising results in Merkel cell polyomavirus (MCPyV)-negative MCC patients with TMB-H, while pembrolizumab therapy has shown better response in patients with low TMB. A study evaluating neoadjuvant nivolumab therapy found no significant difference in treatment response between the tumor etiologies and TMB levels. In addition to ICI therapy, other treatments that induce apoptosis, such as milademetan, have demonstrated positive responses in MCPyV-positive MCC, with few somatic mutations and wild-type TP53. This review summarizes current knowledge and discusses emerging and potentially predictive biomarkers for MCC therapy with ICI.

The role of the tumor microenvironment (TME) in immuno‐oncology has driven demand for technologies that deliver in situ, or spatial, molecular information. Compartmentalized heterogeneity that traditional methods miss is becoming key to predicting both acquired drug resistance to targeted therapies and patient response to immunotherapy. Here, we describe a novel method for assay‐agnostic spatial profiling and demonstrate its ability to detect immune microenvironment signatures in breast cancer patients that are unresolved by the immunohistochemical (IHC) assessment of programmed cell death ligand‐1 (PD‐L1) on immune cells, which represents the only FDA microenvironment‐based companion diagnostic test that has been approved for triple‐negative breast cancer (TNBC). Two distinct physiological states were found that are uncorrelated to tumor mutational burden (TMB), microsatellite instability (MSI), PD‐L1 expression, and intrinsic cancer subtypes.

Colorectal cancer (CRC) is the third leading cause of mortality worldwide. The Food and Drug Administration recently designated pembrolizumab, an immune checkpoint inhibitor (ICI) against a programmed death-1 receptor, as a breakthrough drug for the treatment of patients with mCRC whose tumors have deficient mismatch-repair gene expression (as evidenced by microsatellite instability-high) and patients with solid tumors with a high tumor mutational burden with ≥10 mutations/megabase. We present a patient with metastatic CRC having renal and adrenal gland metastases. Comprehensive molecular profiling performed on a site of metastatic CRC in the kidney revealed multiple genomic alterations characteristic of CRC and rare chromosome 9p24.1 amplification, resulting in a co-amplification of the PDL1, PDL2, and JAK2 genes. Although this genomic alteration may predict the response to ICI, the lack of pembrolizumab prevented the patient from receiving targeted treatment and succumbing to the disease.

Small cell lung cancer (SCLC) is a highly aggressive malignancy with a poor outcome. We present the case of a 57-year-old male patient with extensive-stage (ES-SCLC) treated with chemotherapy and atezolizumab. A complete response was achieved with a long remission of ∼three years. Comprehensive genomic profiling (CGP) of the tumor revealed high tumor mutation burden (13 mutations/Mb) and mutations of TP53, RB1 and ERCC4 genes. This case study confirms that a complete response to chemoimmunotherapy may be achieved in the case of ES-SCLC. It further provides the additional value of CGP and predictive testing in the management of ES-SCLC.

Simple Summary Peptides are ubiquitous molecules abundantly found in nature, and their diverse functions and biological activities have been extensively examined over the years. In the past, in vitro and in vivo biological effects of flaxseed oil have been well-examined and reported in numerous studies. However, the effects of many individual components from the flaxseed are yet to be examined. Cyclolinopeptides (CLPs), one of the components, have gained significant attention due to their cyclic nature and hydrophobic properties. CLPs are isolated from flaxseed and typically consist of eight, nine, or ten amino acid residues. Experimental investigations into the biological activities of CLPs began in the 1980s and early 1990s, revealing their potential therapeutic applications. In recent years, particularly, there has been interest in examining the anticancer effect of CLPs. Diverse bioactivities and potential therapeutic CLPs aspects seek novel approaches and further investigation to maximize utility. Abstract Novel therapeutic agents to combat cancer is an active area of research, as current treatment options have limitations in efficacy and tolerability. One of these therapeutic agents in our immediate environment is cyclolinopeptides (CLPs). CLPs have several advantages that make them suitable for daily consumption and potential therapeutics in cancer research. They are natural compounds, having high specificity, low toxicity, low cost, and an overall simple extraction process. Over the years, numerous in vitro studies in cancer cells demonstrated CLPs to possess anti-proliferative, apoptotic, and anti-angiogenic effects, as well as the ability to induce cell cycle arrest and inhibit cancer cell growth in various cancer types, including breast cancer, gastric cancer, and melanoma. This paper provides an overview of the significance and potential of CLPs as therapeutic agents, emphasizing their promising role in cancer treatment based on different cancer cell lines. The mechanism of action of CLPs in cancer cells is multifaceted. It involves the modulation of multiple signaling pathways, including inhibition of protein kinases, modulation of apoptosis-related proteins, and regulation of oxidative stress and inflammation.

Small cell lung cancer (SCLC) is an aggressive malignancy characterized by rapid proliferation, early dissemination, acquired therapy resistance, and poor prognosis. Early diagnosis of SCLC is crucial since most patients present with advanced/metastatic disease, limiting the potential for curative treatment. While SCLC exhibits initial responsiveness to chemotherapy and radiotherapy, treatment resistance commonly emerges, leading to a five-year overall survival rate of up to 10%. New effective biomarkers, early detection, and advancements in therapeutic strategies are crucial for improving survival rates and reducing the impact of this devastating disease. This review aims to comprehensively summarize current knowledge on diagnostic options, well-known and emerging biomarkers, and SCLC treatment strategies and discuss future perspectives on this aggressive malignancy.

ABSTRACT High-risk Human Papillomaviruses (HPVs) and Epstein – Barr virus (EBV) are present and involved in several types of human carcinomas, including cervical and, head and neck cancers. Nevertheless, their presence and association in the pathogenesis of colorectal cancer is still nascent. The current study explored the association between the high-risk HPVs and EBV and tumor phenotype in colorectal cancers (CRCs) in the Qatari population. We found that high-risk HPVs and EBV are present in 69/100 and 21/100 cases, respectively. Additionally, 17% of the cases showed a copresence of high-risk HPVs and EBV, with a significant correlation only between the HPV45 subtype and EBV (p = .004). While the copresence did not significantly associate with clinicopathological characteristics, we identified that coinfection with more than two subtypes of HPV is a strong predictor of advanced stage CRC, and the confounding effect of the copresence of EBV in such cases strengthens this association. Our results indicate that high-risk HPVs and EBV can co-present in human CRCs in the Qatari population where they could plausibly play a specific role in human colorectal carcinogenesis. However, future studies are essential to confirm their copresence and synergistic role in developing CRCs.

Highlights • We report a case of a patient with acute myeloid leukemia (AML) presenting as myeloid sarcoma.• This patient with bilateral adnexal masses was managed via total robotic hysterectomy with bilateral salpingo-oophorectomy.• There are a limited number of reports of bilateral ovarian occurrences that exist in the literature.• Myeloid sarcoma of the ovaries may present with vaginal bleeding to dysmenorrhea, dysuria, and palpable abdominal mass.

High-risk human papillomaviruses (HPVs) are considered risk factors in the origin of several human malignancies, such as breast, cervical, head and neck, as well as colorectal cancers. However, there are no data reported on the HPV status in colorectal cancer in the State of Qatar. Therefore, we herein examined the presence of high-risk HPVs (16, 18, 31, 33, 35, 45, 51, 52, and 59), using polymerase chain reaction (PCR) in a cohort of 100 Qatari colorectal cancer patients, and their association with tumor phenotype. We found that high-risk HPV types 16, 18, 31, 35, 45, 51, 52, and 59 were present in 4, 36, 14, 5, 14, 6, 41, and 17% of our samples, respectively. Overall, 69 (69%) of the 100 samples were HPV positive; among these, 34/100 (34%) were positive for single HPV subtypes, while 35/100 (35%) of the samples were positive for two or more HPV subtypes. No significant association was noted between the presence of HPV and tumor grade, stage, or location. However, the presence of coinfection of HPV subtypes strongly correlated with advanced stage (stage 3 and 4) colorectal cancer, indicating that the copresence of more than one HPV subtype can significantly worsen the prognosis of colorectal cancer. The results from this study imply that coinfection with high-risk HPV subtypes is associated with the development of colorectal cancer in the Qatari population.

Objective: Sacrococcygeal teratoma is an extragonadal germ cell tumor that develops during fetal and neonatal periods and is associated with significant perinatal morbidity and even mortality. This study aimed to determine the clinicopathologic characteristics, the clinical outcomes, and postoperative complications of sacrococcygeal teratoma cases in the low-volume pediatric surgery service in a developing country. Materials and Methods: The study included data from all sacrococcygeal teratoma cases diagnosed from 2011 to 2020. All the relevant clinicopathologic data were recorded and analyzed. Results: A total of 7 pediatric (5 females and 2 males) patients with sacrococcygeal teratoma were identified, ranging in age from 3 to 222 days. A prenatal diagnosis was made in 57.1% of cases. The mean gestational age for all cases was 37.1 weeks (34-38 weeks), and the mean birth weight was 3285 g (range, 2300-4700 g). Preoperative alpha-fetoprotein levels had a mean value of 24.327 ng/mL (range, 649.7-110.600 ng/mL). The surgery involved resection of the primary tumor and coccygectomy in all cases. Three (42.9%) tumors were classified as Altman type II lesions, 2 (28.6%) tumors were type IV, and 2 remaining cases were types I and III, respectively. Histology was benign in 4 (57.1%) and immature in 3 patients (42.9%). The mean follow-up time was 101.4 months (30-146 months), with 2 recurrences of high-grade immature teratomas at 11 and 30 months following the surgery. Three patients had postoperative bladder and rectal dysfunctions. Conclusion: Sacrococcygeal teratomas are rare tumors associated with frequent postoperative dysfunctions. Recurrences may also be seen, particularly in immature, high-grade forms of sacrococcygeal teratomas.