Mirvetuximab soravtansine-gynx (MIRV) is a first-in-class, folate receptor alpha (FRα)-targeting antibody-drug conjugate with United States Food and Drug Administration approval for FRα-positive platinum-resistant ovarian cancer. PICCOLO is a phase II, global, open-label, single-arm trial of MIRV as third-line or greater (≥3L) treatment in patients with FRα-positive (≥75% of cells with ≥2+ staining intensity) recurrent platinum-sensitive ovarian cancer (PSOC). Participants received MIRV (6 mg/kg adjusted ideal body weight every 3 weeks) until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death. Primary endpoint was investigator-assessed objective response rate (ORR). Key secondary endpoint was investigator-assessed duration of response (DOR). Additional endpoints included investigator-assessed progression-free survival (PFS), overall survival (OS), and safety. Analyses of subgroups by disease characteristics (e.g. platinum-free interval) and treatment history [e.g. prior bevacizumab and poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitor (PARPi) treatment] were exploratory. Seventy-nine participants were enrolled and efficacy assessable. The primary endpoint was met; ORR was 51.9% [95% confidence interval (CI) 40.4% to 63.3%]. Median DOR was 8.25 months (95% CI 5.55-10.78 months) and median PFS was 6.93 months (95% CI 5.85-9.59 months). OS was not mature at data cut-off. ORR was 45.8% (95% CI 32.7% to 59.2%) in participants with PD while on/within 30 days of prior PARPi (n = 59) and 60.0% (95% CI 14.7% to 94.7%) in those without PD with prior PARPi (n = 5). No new safety signals occurred; most common treatment-emergent adverse events (TEAEs) were gastrointestinal, neurosensory, and resolvable ocular events. TEAEs led to discontinuation in 13 participants (16%) and death in 2 participants (3%). MIRV as ≥3L treatment in heavily pretreated recurrent FRα-positive PSOC demonstrated notable efficacy and tolerable safety, including among those with prior PD on or within 30 days of PARPi (NCT05041257).

In recent years, the incorporation of new strategies to the therapeutic armamentarium has completely changed the outcomes of epithelial ovarian cancer (EOC). The identification of new predictive and prognostic biomarkers has also enabled the selection of those patients more likely to respond to targeted agents. Nevertheless, EOC is still a highly lethal disease and resistance to many of these new agents is common. The objective of this guideline is to summarize the most relevant strategies to manage EOC, to help the clinician throughout the challenging diagnostic and therapeutic processes and to provide evidence-based recommendations.

Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. Although most cases are diagnosed at an early stage, prognosis in case of relapse or metastasis remains poor. Molecular characterization of EC is highly recommended as it allows more accurate risk stratification and may modify treatment recommendations. The updated FIGO 2023 staging of EC highlights the importance of traditional clinicopathological factors, while underlining the need for molecular classification to predict outcomes. In early-stage EC, standard treatment consists of total hysterectomy and bilateral salpingo-oophorectomy. Lymph node evaluation remains controversial, as the benefits of systematic lymphadenectomy are unclear. Adjuvant treatment, consisting of radiotherapy, brachytherapy, and chemotherapy, should be chosen according to risk category. In women with advanced or recurrent EC, the combination of carboplatin and paclitaxel has long been standard treatment. However, therapeutic options have changed recently due to advances in immunotherapy. The aim of this guideline is to summarize the current evidence for the diagnosis, treatment, and follow-up of EC, and to provide evidence-based recommendations for clinical practice.

Autophagy is a fundamental cellular process that maintains homeostasis by degrading damaged components and regulating stress responses. It plays a crucial role in cancer biology, including tumor progression, metastasis, and therapeutic resistance. Oxidative stress, similarly, is key to maintaining cellular balance by regulating oxidants and antioxidants, with its disruption leading to molecular damage. The interplay between autophagy and oxidative stress is particularly significant, as reactive oxygen species (ROS) act as both inducers and by-products of autophagy. While autophagy can function as a tumor suppressor in early cancer stages, it often shifts to a pro-tumorigenic role in advanced disease, aiding cancer cell survival under adverse conditions such as hypoxia and nutrient deprivation. This dual role is mediated by several signaling pathways, including PI3K/AKT/mTOR, AMPK, and HIF-1α, which coordinate the balance between autophagic activity and ROS production. In this review, we explore the mechanisms by which autophagy and oxidative stress interact across different hematological malignancies. We discuss how oxidative stress triggers autophagy, creating a feedback loop that promotes tumor survival, and how autophagic dysregulation leads to increased ROS accumulation, exacerbating tumorigenesis. We also examine the therapeutic implications of targeting the autophagy-oxidative stress axis in cancer. Current strategies involve modulating autophagy through specific inhibitors, enhancing ROS levels with pro-oxidant compounds, and combining these approaches with conventional therapies to overcome drug resistance. Understanding the complex relationship between autophagy and oxidative stress provides critical insights into novel therapeutic strategies aimed at improving cancer treatment outcomes.

Genomic Instability (GI) is a transversal phenomenon shared by several tumor types that provide both prognostic and predictive information. In the context of high-grade serous ovarian cancer (HGSOC), response to DNA-damaging agents such as platinum-based and poly(ADP-ribose) polymerase inhibitors (PARPi) has been closely linked to deficiencies in the DNA repair machinery by homologous recombination repair (HRR) and GI. In this study, we have developed the Scarface score, an integrative algorithm based on genomic and transcriptomic data obtained from the NGS analysis of a prospective GEICO cohort of 190 formalin-fixed paraffin-embedded (FFPE) tumor samples from patients diagnosed with HGSOC with a median follow up of 31.03 months (5.87–159.27 months). In the first step, three single-source models, including the SNP-based model (accuracy = 0.8077), analyzing 8 SNPs distributed along the genome; the GI-based model (accuracy = 0.9038) interrogating 28 parameters of GI; and the HTG-based model (accuracy = 0.8077), evaluating the expression of 7 genes related with tumor biology; were proved to predict response. Then, an ensemble model called the Scarface score was found to predict response to DNA-damaging agents with an accuracy of 0.9615 and a kappa index of 0.9128 (p < 0.0001). The Scarface Score approaches the routine establishment of GI in the clinical setting, enabling its incorporation as a predictive and prognostic tool in the management of HGSOC.