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Introduction: The clinical outcome of HER2-positive breast cancer patients changed with the use of anti-Her therapies, though it still remains an aggressive and fatal disease. Implementation of immune checkpoint inhibitors in HER2-positive Breast cancer is a concept supported by the reported biological and preclinical data. Methods: We conducted a systematic review of the current literature involving immune checkpoint inhibitors alone or in combination with targeted therapies or chemotherapy finalized or running in HER2-positive breast cancer. Results: Twelve clinical trials and 2 case reports were identified in our study. Conclusion: The reported clinical trials highlight that checkpoint inhibition seems to be promising in metastatic, neoadjuvant, and adjuvant settings of HER2-positive breast cancer. [ABSTRACT FROM AUTHOR]

Background: The Hippo pathway is a developmental pathway recently discovered in Drosophila melanogaster; in mammals it normally controls organ development and wound healing. Hippo signaling is deregulated in breast cancer (BC). MST1/2 and LATS1/2 kinases are the upstream molecular elements of Hippo signaling which phosphorylate and regulate the two effectors of Hippo signaling, YAP1 and TAZ cotranscriptional activators. The two molecular effectors of the Hippo pathway facilitate their activity through TEAD transcription factors. Several molecular pathways with known oncogenic functions cross-talk with the Hippo pathway. Methods: A systematic review studying the correlation of the Hippo pathway with BC tumorigenesis, prognosis, and treatment was performed. Results: Recent literature highlights the critical role of Hippo signaling in a wide spectrum of biological mechanisms in BC. Discussion: The Hippo pathway has a crucial position in BC molecular biology, cellular behavior, and response to treatment. Targeting the Hippo pathway could potentially improve the prognosis and outcome of BC patients. [ABSTRACT FROM AUTHOR]

Background: nasopharyngeal carcinoma (NPC) is a complex disease entity that mainly predominates in endemic regions. Real-world data with immunotherapy from nonendemic regions are limited. Methods: we collected data from patients with recurrent/metastatic (R/M) NPC treated at a center in Greece and 8 centers in Italy. Between 2016 and 2021, 46 patients who were treated with at least one cycle of immune checkpoint inhibitors (ICI) were identified. Herein, we present our results and a review of the literature. Results: assessment of response was available in 42 patients. Overall, 11 patients responded to immunotherapy (Overall Response Rate-ORR 26.2%). Three patients had complete response (CR), and 8 patients had partial response (PR). Disease control rate (DCR) was 61.9%. Median Progression Free Survival (PFS) was 5.6 months and median Overall Survival (OS) was 19.1 months. Responders to ICI improved PFS and OS as compared to that of nonresponders. A lower probability of responding to ICI was shown in patients with more than three metastatic sites (p = 0.073), metastatic disease at initial diagnosis, (p = 0.039) or EBV DNA positive before ICI initiation, (p = 0.074). Decline in EBV DNA levels was found to be statistically significant associated with best response to ICI (p = 0.049). Safety was manageable. Conclusions: among 46 patients with R/M NPC treated with immunotherapy in two nonendemic regions, ORR was 26.2% and durable responses were observed. Low disease burden could serve as a biomarker for response to ICI. [ABSTRACT FROM AUTHOR]

Background/aim: Uterine leiomyosarcomas (uLMS) are the most common mesenchymal tumors of the female genital tract. uLMS genetics encompass complex karyotypes with no specific molecular alterations. The Hippo pathway has been implicated in the pathogenesis of epithelioid hemangio-endotheliomas and endometrial sarcomas. Hippo pathway effectors are YAP1 and TAZ co-transcriptional factors., Patients and Methods: We studied Hippo pathway in a series of 32 uLMS patients and its association with clinicopathological parameters., Materials and Methods: Immunohistochemical analysis of YAP1 and TAZ proteins accompanied with fluorescent in situ hybridization study of YAP1 gene was performed in patient samples. Age, sex, tumor size, stage at the time of diagnosis and treatment have been analyzed. Overall survival (OS) was calculated from the time of diagnosis until death, loss of follow up or data cut-off., Results: Hippo signaling was found to be dysregulated in 20 (62.5%) patients with uLMS. Regarding OS we detected a trend of Hippo deregulation, designating it as a positive prognostic factor., Conclusion: The Hippo pathway is implicated in uLMS oncogenesis, since nuclear expression of YAP1 was detected in 17 (53.1%) of the 32 patients with immunohistochemistry and YAP1 amplification was found in 8 (25%) patients., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The diagnosis and management of patients with a clear cell sugar tumor of the lung (CCSTL) is challenging in the clinical practice due to its rarity., Methods: We performed a systematic review on this field according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We sought eligible articles in Medline through January 1st, 2019., Results: Overall, 104 CCSTL cases were identified and included in the present study. The median age at diagnosis was 52 years (interquartile range 42.5-62.5), whereas the cases were almost equally distributed among males (n=48) and females (n=49). Most of the tumors were asymptomatic (60.7%) and had a benign clinical course (73.3%). Complete tumor resection with a curative intent was the treatment of choice and pathology along with immunohistochemical indices established the diagnosis. However, long-term follow up is recommended, especially among patients with underlying genetic diseases, because disseminated disease may become evident many years following the resection of the primary lesions. Furthermore, an extensive workup for excluding metastasis from another occult primary site is necessary. The updated classification of lung neoplasms has enabled the more frequent reporting of CCSTL cases in the last decade. Interestingly, our time trend analysis showed an increase in malignant cases throughout the years., Conclusion: Both collaborative multicenter studies and basic research on the underlying pathogenetic mechanisms are deemed necessary in order to optimize the diagnosis and personalize the management of patients with this rare entity.

Purpose: Herein, we critically evaluate and discuss current literature in the field of human papillomavirus (HPV) pathogenesis, treatment, and prevention., Methods: Screening of the literature and selection of studies was performed until May 31st, 2019., Results: HPV is considered the commonest heterosexual and homosexual sexually transmitted infection globally. Low-risk HPV subtypes are associated with genital warts, whereas persistent infection with high-risk HPV 16 and 18 subtypes is closely associated with premalignant and invasive lesions in the anogenital and oropharyngeal region. E6 and E7 genes are the main drivers of oncogenic transformation in cervix since they promote all aspects of cancer hallmarks. Importantly, the implementation of screening has reduced the HPV-associated disease burden. In this field, a shift from cytology to HPV testing is currently being observed. Furthermore, vaccination programmes have shown high effectiveness in preventing HPV infection and HPV-related lesions, whereas their future implementation on a larger scale would further enhance our primary prevention strategies., Conclusion: Although HPV constitutes an evolving paradigm in cancer prevention, optimizing screening test performance, and cost-effectiveness remains debatable.

Secondary chondrosarcoma is a malignant chondroid tumor arising in a benign precursor. Synovial chondromatosis is a benign chondroid lesion that rarely transforms to chondrosarcoma. We present the case of a 54-year-old male with the diagnosis of low-grade secondary peripheral chondrosarcoma developed in the context of synovial chondromatosis. Cytogenetics revealed a novel aberration t(1;14)(q23.1~24;q24.1~3). Multicolor banding (mBAND) analysis described the chromosomal regions involved in this translocation with a higher detail. Diagnosis of such borderline lesions is very difficult and cytogenetics is helpful in characterizing these tumors.