Ovarian cancer is the most lethal gynecologic malignancy, primarily because of late-stage diagnosis, rapid disease progression, and marked molecular and immunologic heterogeneity. It remains the leading cause of gynecologic cancer-related death, affecting approximately 1 in 70 women in developed countries over their lifetimes. Tumor development and progression are orchestrated within the tumor immune microenvironment, a dynamic and complex structural niche that supports malignant transformation and immune evasion of the tumor. In this narrative educational review, we aim to provide a comprehensive overview of recent advances in the understanding of ovarian cancer pathogenesis, the molecular mechanisms driving tumor progression, and the multifaceted role of the immune system in disease development and therapeutic response. Moreover, we summarize recent clinical trials targeting key molecular drivers and components of the tumor immune microenvironment, including immunotherapeutic and targeted approaches. Personalized medicine, guided by integrative genomic and transcriptomic profiling, has become increasingly vital for patient stratification and treatment selection. Ultimately, a shift toward highly individualized, mechanism-based therapeutic strategies is essential to improve clinical outcomes and survival in ovarian cancer.
B. Vavrušáková, R. Bartošová, M. Hendrych et al.· Discover Oncology· 0 citations
Background Patients with a history of extracranial cancers (EXCA) who develop new intracranial lesions are commonly presumed to harbour brain metastases, yet primary glioblastoma (GBM) can also arise de novo in cancer survivors. The clinical course, molecular features, and treatment outcomes of GBM in this population remain incompletely characterised. Methods We retrospectively analysed adult patients with concurrent prior solid EXCA and supratentorial GBM treated at three Czech neuro-oncology centres between January 2010 and December 2022. Patients with hematologic malignancies or needle-biopsy-only diagnoses were excluded. Demographic, clinical, molecular (IDH, MGMT), surgical (RANO RESECT 2022 extent-of-resection classification), and treatment data were collected and related to progression-free survival (PFS) and overall survival (OS) using Kaplan–Meier estimation, log-rank tests, and Cox regression. Results Of 1,182 patients operated for GBM, 48 (4.0%) had a documented prior solid EXCA. Median age at EXCA diagnosis was 57.5 years (range 21–82); median age at GBM diagnosis was 65 years (range 46–82). The median interval between diagnoses was 5.7 years (range 0.1–27.3). All 48 GBMs were IDH-wildtype; MGMT promoter status was assessable in 23 cases (17 unmethylated, 6 methylated), of which 22 had follow-up data available for survival analysis. Median PFS was 8.4 months (95% CI 7.6–27.3) and median OS was 10.6 months (95% CI 5.7–16.8). MGMT methylation (mOS 29.3 vs 12.0 months; p = 0.037), higher Karnofsky score, more radical surgical resection, and completion of the Stupp protocol (mOS 19.2 vs 2.5 months for no oncotherapy; p = 0.019) were each significantly associated with longer OS. Conclusions A new brain lesion in a cancer survivor must not be assumed to be metastatic without histological confirmation. When patients with GBM after prior EXCA are eligible for standard radical surgery and Stupp-protocol oncotherapy, survival outcomes are comparable to those reported for sporadic GBM. Standard treatment protocols are appropriate for this population; a history of extracranial cancer is not in itself an adverse prognostic factor.
Ondřej Kalita, Tomas Kazda, S. Tomoszková et al.· Frontiers in Oncology· 0 citations
