Fernando Gálvez-Montosa

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.

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.

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.

A 68-year-old man is being treated with cisplatin-pemetrexed in the first line for bone metastatic lung adenocarcinoma. There is partial response and very good tolerance with no grade 3–4 toxicities. After six cycles of doublet therapy, the patient follows on pemetrexed maintenance. Six months later, he develops a hot and itchy rash with poor response to corticoids and topical antibiotics. Quiz option A: Skin toxicity to cisplatin Quiz option B: Skin toxicity to pemetrexed Quiz option C: Erysipelas Quiz option D: Carcinoma erysipeloides Quiz option E: Inflammatory breast cancer Quiz option F: Cellulitis