Oncoscience最新文献

{"title":"Targeting leucine-rich alpha-2-glycoprotein-1 (LRG1) and the LRG1-cytochrome <i>c</i>-Apaf-1 axis in cancer therapy.","authors":"Ronald Jemmerson","doi":"10.18632/oncoscience.667","DOIUrl":"10.18632/oncoscience.667","url":null,"abstract":"<p><p>Leucine-rich alpha-2-glycoprotein-1 (LRG1) has received much attention as a prognostic indicator in cancer therapy where high serum levels generally predict a poor outcome. Recently, it has been shown to play an active role in cancer progression and is being pursued as a novel target in cancer therapy. LRG1 acts in neovascularization of tumors resulting in weakened blood vessels and ineffective delivery of chemotherapeutic drugs. A monoclonal antibody (mAb) against LRG1 has shown efficacy in blocking this function of LRG1, normalizing the vasculature, and improving drug delivery in mice. Extracellular LRG1 is also anti-apoptotic and promotes cell proliferation and metastasis, all through epidermal growth factor receptor family signaling. In mice, anti-LRG1 antibody therapy has been shown to inhibit these effects of extracellular LRG1 and to enhance the anti-cancer effect of immune checkpoint blockade (ICB) therapy in mice. Pre-clinical testing of the humanized version of the LRG1 mAb is underway in the United Kingdom. Intracellular LRG1 has been reported to inhibit apoptosis by blocking the binding of Cyt <i>c</i> to apoptotic protease activating factor1 (Apaf-1) and to have other cytoplasmic functions. A nanoscale proteolysis targeting chimera (nano-PROTAC) with improved cytoplasmic delivery has been developed which enhanced apoptosis in tumors of mice. Targeting LRG1 in the aberrant angiogenesis of endothelial cells and the LRG1-Cyt <i>c</i>-Apaf-1 axis in cancer cells, along with other putative intracellular interactions of LRG1, show potential as supplementary, if not alternative, approaches to cancer therapy.</p>","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"13 ","pages":"250-259"},"PeriodicalIF":0.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13426073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering CAR-T cells for solid tumors: Overcoming the microenvironment through integrated design and clinical translation.","authors":"Samuel Obiosa Onyekweli, Gloria Osayamen Omoruyi, Christopher Oloruntoba Akintayo, Samuel Kehinde Olaniyi","doi":"10.18632/oncoscience.666","DOIUrl":"10.18632/oncoscience.666","url":null,"abstract":"<p><p>Chimeric antigen receptor T-cell (CAR-T) therapy has produced remarkable therapeutic results in blood cancers, while its application to solid malignancies remains limited by a pooled objective response rate of approximately 9%. This gap stems from core biological obstacles: heterogeneous antigen expression, physical inaccessibility within dense stromal architectures, and immunosuppressive microenvironments that drive T-cell exhaustion through epigenetically fixed transcriptional programs. The period spanning 2024-2025 represents a pivotal turning point. GD2-targeting CAR-T cells delivered intracerebroventricularly achieved durable complete responses (including one sustained beyond 30 months) in H3K27M-mutated diffuse midline gliomas. CLDN18.2-targeting satricabtagene autoleucel demonstrated randomized superiority over physician's choice in advanced gastric cancer (progression-free survival HR 0.37). GPC3-targeting CAR-T cells armored with a dominant-negative TGF-β receptor achieved objective response rates of 50-57% in hepatocellular carcinoma, representing a three- to four-fold improvement over unarmored predecessors. These breakthroughs reflect a paradigm shift from potency-driven engineering toward resilience-based design: metabolic armoring via autocrine IL-10 and IL-15, epigenetic protection through DNMT3A disruption and c-Jun overexpression, logic-gated targeting via synNotch circuits, and microenvironmental shielding through dominant-negative receptors. Beyond the local microenvironment, emerging recognition of systemic neuroendocrine-immune dysregulation further informs CAR-T persistence and fitness considerations. This review synthesizes the mechanistic insights, engineering strategies, clinical evidence, and emerging platforms, including <i>in vivo</i> lentiviral CAR-T generation, that define the current landscape, and proposes a tiered framework for next-generation solid tumor CAR-T development, while explicitly acknowledging the limitations and unknowns that persist.</p>","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"13 ","pages":"227-249"},"PeriodicalIF":0.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13426074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRI in deciphering the superficial spread of cervical squamous cell carcinoma into the uterine corpus: A case report and literature review.","authors":"Naina Kumar, Aparna Jarathi, Shailaja Prabhala, Annapurna Srirambhatla","doi":"10.18632/oncoscience.668","DOIUrl":"10.18632/oncoscience.668","url":null,"abstract":"<p><p>We report a deceptive presentation of Squamous Cell Carcinoma of the Cervix in a 54-year-old postmenopausal woman who presented with postmenopausal bleeding associated with lower abdominal pain for a 3-month duration, with a normal-looking ectocervix. She was diagnosed with squamous cell carcinoma on a pap smear and cervical biopsy. Magnetic resonance imaging revealed an irregular endometrial cavity contour, and a T2 hyperintense lesion was seen (2.3 × 0.8 cm) involving the posterior lip of the cervix at the junction of stroma and endocervix with a mural spread along the uterine myometrium. Histopathology after Wertheim's hysterectomy revealed a squamous cell carcinoma of the endocervix, Stage pT1b3, that had spread superficially to the endometrium, myometrium, and left salpinx. The detection of immunohistochemical expression of p16, p63, and negative for ER and PR in the lesions of the cervix and the endometrium suggests that these two lesions are etiologically related, favoring the possibility of endometrial SCC secondary to cervical SCC.</p>","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"13 ","pages":"260-269"},"PeriodicalIF":0.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13426071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endometrial carcinosarcoma with multi-classifier molecular signature (MMRd-p53abn): A case report.","authors":"Aparna Jarathi, Akhila Pagolu, Naina Kumar, Shrinivas Somalwar, Sai Swetha Banka, Nireesha Bukke, Chandramouli Ramalingam","doi":"10.18632/oncoscience.665","DOIUrl":"10.18632/oncoscience.665","url":null,"abstract":"<p><p>The uterine carcinosarcoma is a rare biphasic Malignant Mixed Mullerian Tumour (MMMT). It is a highly aggressive endometrial cancer phenotype, consisting of both epithelial and mesenchymal components. The presented case refers to a 65-year-old, P6L3 postmenopausal woman with postmenopausal bleeding and white discharge per vagina for one month with vulval leukoplakia. The ultrasound showed a thickened endometrium measuring 15 mm, and the Magnetic Resonance Imaging showed the uterus measuring 7.4 × 4.5 × 6 cm. The endometrium appeared heterogeneous, with a hyperintense lesion measuring 4.8 × 2.3 cm on T2W1. The myometrium appeared normal, and neither of the ovaries was visualized. The patient underwent surgery. The histopathological and immunohistochemical analysis suggested that high-grade Endometrial Carcinosarcoma with dual classifier positivity (MMRd-p53abn) more closely resembled single-classifier MMRd (Mismatch repair deficiency) than p53abn, with a good prognosis. Post-surgery, the patient was followed up on every three months. The patient received 6 cycles of adjuvant chemotherapy. Considering the highly invasive nature of uterine carcinosarcomas, the timely detection of this cancer by imaging, pathology findings and molecular classification is of extreme importance to improve the patient's survival and for management outcome.</p>","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"13 ","pages":"220-226"},"PeriodicalIF":0.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13426072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cultural carcinogens in oral squamous cell carcinoma risk across global populations.","authors":"Nicole C Nowak, Alyssa Forsyth, Brooke Blan, Shivani S Ambardekar, Kelly Frasier, Nicole Werpachowski, Adrian P Mansini","doi":"10.18632/oncoscience.662","DOIUrl":"10.18632/oncoscience.662","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide, leading to significant illness and death, particularly in low- and middle-income countries. In addition to tobacco, alcohol, and human papillomavirus (HPV), several culturally ingrained practices, such as areca nut chewing, toombak, khat, reverse smoking, and hot mate drinking, remain underrecognized but important cultural factors contributing to OSCC globally. These exposures operate through the formation of nitrosamine-induced DNA adducts, oxidative stress, chronic inflammation, and thermal injury. Areca nut and toombak are associated with oral submucous fibrosis and carcinoma, while reverse smoking and mate are linked to thermal and polycyclic aromatic hydrocarbon-related effects. Khat is connected to oxidative and cytogenetic damage. This narrative review combines epidemiological, mechanistic, and public health evidence on cultural carcinogens in OSCC, emphasizing prevention strategies that honor cultural identity through education, harm reduction, and community involvement. Dermatologists specializing in mucocutaneous oncology can detect early lesions like leukoplakia, erythroplakia, and oral submucous fibrosis. Including oral mucosal screening in routine care provides an effective, affordable way to prevent diseases in high-risk populations. Culturally sensitive, dermatology-focused prevention can help reduce OSCC incidence and disparities while respecting community identity.</p>","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"13 ","pages":"210-219"},"PeriodicalIF":0.0,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13248716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The dual axis of tumorigenesis: MAPK and PI3K/AKT pathways in papillary thyroid carcinoma.","authors":"Gunvanti Rathod, Pragnesh Parmar","doi":"10.18632/oncoscience.663","DOIUrl":"10.18632/oncoscience.663","url":null,"abstract":"<p><p>The MAPK and PI3K/AKT pathways are important components in cell growth and proliferation, which, when activated, result in cancer formation. Molecular alterations are the main cause of activation of the MAPK and PI3K/AKT pathways in the development of papillary thyroid carcinoma (PTC), the most common endocrine cancer. Activation of the MAPK pathway is usually caused by mutations in the BRAF, RAS, RET/PTC, and NTRK genes, while the activation of the PI3K/AKT pathway results from alterations in the PIK3CA, PTEN, and AKT genes. Moreover, hyperactivation of the MAPK pathway can be caused by overexpression of RTKs, GPCRs, and mutation in PTEN. Interactions between the two signaling pathways exacerbate tumor aggressiveness, dedifferentiation, radioiodine resistance, and response to targeted therapy in PTC. Recent developments in personalized medicine, including the introduction of new molecular diagnostic tools and targeted agents, have made considerable progress in the risk stratification and treatment strategies for papillary thyroid carcinoma. The current article reviews molecular mechanisms of activation of MAPK and PI3K/AKT pathways, their interaction, clinicopathological importance, and targeted treatments in papillary thyroid carcinoma.</p>","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"13 ","pages":"194-204"},"PeriodicalIF":0.0,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13248687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adaptor proteins regulating tumor-associated macrophage polarization during cancer progression.","authors":"Khandu Wadhonkar, Tomokazu Ohishi, Mirza S Baig","doi":"10.18632/oncoscience.661","DOIUrl":"10.18632/oncoscience.661","url":null,"abstract":"<p><p>Adaptor proteins serve as essential molecular scaffolds within the tumor microenvironment, linking activated receptors to downstream signaling pathways and coordinating the assembly of multiprotein complexes that modulate immune responses. Emerging evidence suggests that adaptor proteins play a critical role in shaping macrophage phenotypic plasticity. Tumor-associated macrophages exhibit functional heterogeneity and can adopt either anti-tumorigenic phenotypes that promote immune activation or pro-tumorigenic phenotypes that support tumor growth, metastasis, and immune evasion. The dynamic transition between these functional states is tightly controlled by intracellular signaling networks in which adaptor proteins function as key regulatory nodes. Based on available mechanistic studies, we systematically summarize adaptor molecules that govern signaling pathways driving macrophage polarization within the cancer condition. Additionally, this review underscores the significance of adaptor proteins as key modulators of macrophage phenotype and highlights their potential as therapeutic targets for reprogramming macrophages to enhance anti-tumor immunity. Collectively, we provide a conceptual framework for understanding adaptor-mediated immune regulation in cancer and support the development of targeted strategies to shape the tumor microenvironment.</p>","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"13 ","pages":"177-193"},"PeriodicalIF":0.0,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13248696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cervical angioleiomyoma: A rare tumor behind persistent menorrhagia and pelvic pain.","authors":"Ipsita Mohapatra, Sarojini Raman, Subha Ranjan Samantaray, Mukul Panda","doi":"10.18632/oncoscience.659","DOIUrl":"10.18632/oncoscience.659","url":null,"abstract":"<p><strong>Introduction: </strong>Angioleiomyoma is a rare, benign soft tissue tumor derived from smooth muscle cells with prominent vascular components. While more commonly found in the extremities, angioleiomyomas of the female genital tract, particularly the cervix, are extremely rare. Ultrasound helps in the diagnosis, but MRI is more definitive, as the vascular component of these tumors can often be highlighted with hyper intensity on T2-weighted images. Final confirmation of angioleiomyoma is by histopathological and immunohistochemistry studies.</p><p><strong>Case report: </strong>We present here the diagnosis and management by total excision of a case of a large sized cervical angioleiomyoma in a young female, which presented as persistent heavy menstrual bleeding and pelvic pain.</p><p><strong>Conclusions: </strong>Cervical angioleiomyoma, though rare, should be considered in the differential diagnosis of young females presenting with persistent heavy menstrual bleeding and pelvic pain.</p>","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"13 ","pages":"194-198"},"PeriodicalIF":0.0,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13248686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing breast cancer detection with AI for early diagnosis and recurrence prediction.","authors":"Sidney Andre, Swarda Bandiwadekar, Mrunalini Pattarkine","doi":"10.18632/oncoscience.660","DOIUrl":"10.18632/oncoscience.660","url":null,"abstract":"<p><p>Breast cancer remains one of the leading causes of death among women worldwide, early detection is critical for improving survival. Conventional screening modalities such as mammography, MRI, biopsy, and ultrasound have been pivotal for patient care, but face limitations, including human variability, interpretive errors, operator dependence, and high rates of false positives and negatives which can lead to unnecessary treatment and financial distress. To overcome these challenges, a more accurate and predictive diagnostic tool is needed. This article compares traditional breast cancer screening methods with AI-integrated approaches demonstrating how artificial intelligence enhances diagnostic precision, efficiency, and predictive capability. AI-assisted mammography has been shown to detect 29% more cancers than traditional mammography without increasing false positives and reduces radiologist reading time by 40%. AI-assisted 3D digital breast tomosynthesis detects 1.6 additional cancers per 1,000 screenings and reduces recall rates by 2.2% compared to 2D mammography. In MRI, AI predicted breast cancer development up to one year in advance and correctly localize future cancer sites in 57% of cases. In ultrasound, AI significantly improves diagnostic accuracy, particularly for less experienced radiologists. In biopsy, AI-enabled digital assays for recurrence prediction achieve higher predictive accuracy, with pathologists using AI being 62% faster and 72% more accurate. Integrating AI into breast cancer redefines diagnostic excellence, shifting breast cancer management toward a more proactive, precise, and patient-centered approach. Future research should focus on external validation of AI models across larger and diverse populations, cost-effectiveness to ensure equitable access and ethical consideration to ensure responsible clinical adoption.</p>","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"13 ","pages":"159-176"},"PeriodicalIF":0.0,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13248690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined hepatocellular-cholangiocarcinoma: A rare and challenging diagnostic entity - A Case Report.","authors":"Faten Limaiem, Zied Hadrich, Aziz Atallah, Mohamed Hajri, Sahir Omrani","doi":"10.18632/oncoscience.658","DOIUrl":"10.18632/oncoscience.658","url":null,"abstract":"<p><strong>Background: </strong>Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare and aggressive liver cancer, representing 2-5% of primary hepatic malignancies. Its mixed hepatocytic and cholangiocytic features pose major diagnostic challenges, and the absence of standardized treatment guidelines limits effective management.</p><p><strong>Case presentation: </strong>A 61-yearold man with type 2 diabetes, hypertension, and chronic hepatitis B presented with right hypochondrial pain. Laboratory tests revealed elevated alpha-fetoprotein (247 ng/mL). Imaging showed a heterogeneous mass in liver segment V with capsular retraction, hilar lymphadenopathy, and atypical enhancement. Histological examination of the CT-guided liver biopsy suggested hepatocellular carcinoma. However, this proved to be a key diagnostic pitfall, as the complete resected specimen revealed a mixed tumor: final diagnosis of combined hepatocellularcholangiocarcinoma (cHCC-CCA) with approximately 20% hepatocellular and 80% cholangiocarcinoma components. Clinical Discussion: This case underscores the limitations of preoperative biopsy in diagnosing cHCC-CCA, highlighting the risk of misdiagnosis. Radiological features often reflect the predominant histological component but can be nonspecific due to tumor heterogeneity. Definitive diagnosis requires thorough histopathological examination with immunohistochemistry.</p><p><strong>Conclusions: </strong>cHCC-CCA poses a significant diagnostic and therapeutic challenge. Recognizing this mixed phenotype in complex liver masses is crucial. Histopathological confirmation and complete surgical resection remain key to optimal outcomes. Detailed case reports are essential to improve diagnostic criteria, elucidate molecular biology, and guide evidence-based management for this rare malignancy.</p>","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"13 ","pages":"152-158"},"PeriodicalIF":0.0,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13248711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}