Endometrial cancer (EC) is a heterogeneous disease with a rising incidence worldwide. The understanding of its molecular pathways has evolved substantially since The Cancer Genome Atlas (TCGA) stratified endometrial cancer into four subgroups regarding molecular features: POLE ultra-mutated, microsatellite instability (MSI) hypermutated, copy-number high with TP53 mutations, and copy-number low with microsatellite stability, also known as nonspecific molecular subtype (NSMP). More recently, the International Federation of Gynecology and Obstetrics (FIGO) updated their staging classification to include information about POLE mutation and p53 status, as the prognosis differs according to these characteristics. Other biomarkers are being identified and their prognostic and predictive role in response to therapies are being evaluated. However, the incorporation of molecular aspects into treatment decision-making is challenging. This review explores the available data and future directions on tailoring treatment based on molecular subtypes, alongside the challenges associated with their testing.

Extensive research on homologous-recombination-deficient (HRD) tumors has led to advancements in targeted therapies, such as PARP inhibitors (PARPis). Around 50% of high-grade serous ovarian cancer (HGSOC) cases exhibit HR deficiency, but understanding the remaining half, referred to as homologous-recombination-proficient (HRP) tumors, is limited. This review explores existing knowledge regarding HGSOC patients with HRP tumors and offers insights into potential targets for innovative treatments. Patients with HRP tumors do not experience the same benefits from PARPi and have poorer survival outcomes compared to those with HRD tumors. CCNE1 amplification is a common, well-established molecular feature in HGSOC HRP tumors, occurring in about 20% of cases. Targeting CCNE1 amplification and/or overexpression shows promise with emerging therapies like CDK2 or Wee1 inhibitors. Additionally, approaches using immunotherapy and antibody–drug conjugates could represent promising targets for HRP patients. This review also covers lesser-known molecular features in HRP tumors, such as fold-back inversions and CARM1 amplification and/or overexpression, as well as HRD tumors that acquire HR proficiency (BRCA1/2 reversion mutations, demethylation of BRCA1 and RAD51C). We also discuss controversial topics regarding HRP tumors and limitations of HRD detection. Addressing this need is critical to reduce toxicity and improve disease management.

Despite being a preventable disease, cervical cancer remains a significant public health concern in low- and middle-income countries, including those in Latin America (LATAM), where mortality rates are nearly three times higher than in North America. HPV vaccination represents one of the most important strategies for cervical cancer elimination; however, uptake in these regions has been consistently suboptimal. The aim of this review is to analyze the current status of HPV vaccination programs across LATAM, examines the underlying challenges, and proposes strategies to enhance vaccine coverage. Multiple obstacles to widespread vaccine adoption persist, including limited awareness, cultural stigma, and regional disparities in healthcare access, often driven by socioeconomic and infrastructural limitations. Addressing these challenges through multifaceted interventions—such as school-based vaccination programs, healthcare provider engagement, digital dissemination, simplified dosing schedules, and supportive policy measures—is essential to effectively improve vaccination rates and reduce disease burden.

HER2-positive subtype accounts for 15-20 % of metastatic breast cancer (mBC) cases and is associated with a high incidence of brain metastases (BMs), which affects 35-50 % of the patients, contributing to poor outcomes. Although HER2-targeted therapies have significantly improved overall survival (OS), central nervous system (CNS) involvement remains a significant challenge due to the blood-brain barrier (BBB), which limits systemic treatment efficacy. The advent of antibody-drug conjugates (ADCs) has introduced promising therapeutic options with demonstrated CNS activity. This narrative review synthesizes current evidence on systemic treatments for HER2-positive BMs. A comprehensive literature search included PubMed, ASCO, ESMO, and NCCN guidelines, as well as ongoing trials from ClinicalTrials.gov. Until recently, the HER2CLIMB regimen-combining tucatinib, trastuzumab, and capecitabine-was the most effective option for CNS disease control, achieving a median CNS progression-free survival (PFS) of 9.9 months. However, recent trials highlight the transformative impact of antibody-drug conjugates (ADCs), particularly trastuzumab deruxtecan (T-DXd), in this clinical setting. Pooled analyses from the DESTINY-Breast trials reported intracranial overall response rates (ICORR) of 45.5 % in untreated and 45.2 % in treated BMs. Smaller studies, such as DEBBRA and TUXEDO-1, demonstrated ICORRs of 66.7 % and 73.3 %, respectively, with TUXEDO-1 reporting a median PFS of 14 months. The phase III/IV DESTINY-Breast12 trial further validated T-DXd's efficacy in active BMs, achieving a CNS PFS of 17.3 months and an ICORR of 62.3 %, with the highest responses (82.6 %) in untreated BMs. The current analysis reviews the available data on managing brain metastasis and highlights T-DXd's potential to redefine treatment strategies. It also discusses unanswered questions, such as the role of radiotherapy in asymptomatic disease and the evolving landscape of ADCs.