Triple negative breast cancer (TNBC) represents the breast cancer subtype with least favorable outcome because of the lack of effective treatment options and its molecular features. Recently, ADCs have dramatically changed the breast cancer treatment landscape; the anti-TROP2 ADC Sacituzumab Govitecan has been approved for treatment of previously treated, metastatic TNBC patients. The novel ADC Datopotecan-deruxtecan (Dato-DXd) has recently shown encouraging results for TNBC. In the current paper, we summarize and discuss available data regarding this TROP-2 directed agent mechanism of action and pharmacologic activity, we describe first results on efficacy and safety of the drug and report characteristics, inclusion criteria and endpoints of the main ongoing clinical trials.

Peritoneal metastases (PM) are the spread of tumor forms into the peritoneum as metastases from another organ. PM is a frequent condition in metastatic gastrointestinal cancer (colorectal, gastric, pancreatic, appendiceal, and cholangiocarcinoma); their presence confers a poor prognosis, reducing patient survival. The standard treatment consists of systemic chemotherapy according to current guidelines. In recent years, scientific evidence has shown how combined cytoreductive surgery (CRS) techniques followed by hyperthermic intraperitoneal chemotherapy (HIPEC) can improve survival in this patient population. Despite the results still obtained, using this combined technique is still under discussion. This review aims to highlight the benefits and limitations of this combined procedure, which is already widely used to treat peritoneal metastases in gynecological tumors.

Background: Metastatic colorectal cancer (mCRC) with TP53 gene mutations, which are commonly found in tumors that are microsatellite stable (MSS) and not prone to genetic errors seen in some cancers, is associated with aggressive cancer behavior and poor outcomes. While MSI-high (MSI-H, referring to high levels of gene instability) disease benefits markedly from PD-1-based immunotherapy (drugs that inhibit the PD-1 protein on immune cells), TP53-mutated MSS tumors rarely receive immune checkpoint inhibitors (ICIs, drugs that help immune cells attack cancer) outside of trials and often only in later lines of therapy. Objective: We aimed to synthesize translational and clinical evidence regarding the effects of early rationale-driven immunotherapy combinations on survival outcomes, in TP53-mutated metastatic colorectal cancer, with a focus on practical clinical implications. Methods: This narrative review was conducted in accordance with SANRA criteria. Literature searches were performed in PubMed/MEDLINE, Scopus, and Web of Science (2010–2025). Relevant ESMO and NCCN guidelines and key references were also reviewed. Results: In KEYNOTE-177 study (MSI-H/dMMR), pembrolizumab improved PFS (HR 0.60) and showed durable OS with >5-year follow-up. CheckMate-142 reported sustained activity with nivolumab ± ipilimumab. Preclinical/early clinical data in MSS/TP53 suggest that ICIs may become effective when combined with priming (chemo/DDR) and vascular normalization (anti-VEGF), particularly in subsets with elevated TMB. The randomized ROME trial supports the clinical utility of genomically matched, NGS-guided strategies. Conclusions: A precision approach integrating TP53 status, TMB, and TME modulation could extend the immunotherapy benefit beyond MSI-H to TP53-mutated MSS mCRC; prospective first-line trials are warranted.

Background: Female Sexual dysfunction (FSD) is a common but under-recognized outcome of rectal and anal cancer treatment. While survival has improved, sexual health remains insufficiently addressed in survivorship care, warranting a multidisciplinary perspective. Methods: A narrative review of studies published between 2000 and 2025 was conducted, including clinical trials, cohort studies, and guideline documents addressing female sexual dysfunction after anorectal cancer treatment. Articles that were not pertinent to the research topic, outdated, or methodologically inadequate were excluded from the analysis. Results: Over 60% of female survivors experience FSD, including decreased libido, vaginal dryness, dyspareunia, and arousal difficulties. Causes include hormonal deficiency, nerve injury, and radiation fibrosis, compounded by psychological distress, altered body image, stoma-related stigma, and communication issues. The FSFI is commonly applied but lacks specificity for this population. Geographic disparities persist, with greater stigma and limited care access in low- and middle-income countries. Emerging therapies, such as immunotherapy, may mitigate FSD risk, though evidence is scarce. Conclusions: FSD after anorectal cancer is highly prevalent and significantly impacts quality of life, yet remains under-assessed in follow-up care. Multidisciplinary, culturally sensitive strategies integrating screening, psychosexual support, and tailored rehabilitation are urgently needed. Future research should address sexual outcomes more systematically, particularly in novel treatment contexts.

Therapies targeting human epidermal growth factor receptor 2 (HER2) have substantially improved overall survival in patients with HER2-positive metastatic breast cancer. Approximately 31% of these patients develop brain metastases, representing a significant therapeutic challenge. This review classifies anti-HER2 therapies into three categories: monoclonal antibodies (MABs), antibody-drug conjugates (ADCs), and tyrosine kinase inhibitors (TKIs). The mechanisms of action and clinical impacts of these agents are examined, with particular attention to intracranial efficacy. The introduction of trastuzumab increased overall survival (OS) from 20.3 to 25.1 months compared to chemotherapy alone. The addition of pertuzumab further extended survival to 57.1 months, as demonstrated in the CLEOPATRA trial. Among ADCs, T-DM1 improved OS to 29.9 months versus 25.9 months in the EMILIA trial, while T-DXd extended OS to 52.6 months in DESTINY-Breast03. T-DXd also demonstrated notable intracranial activity, achieving a 64.9% objective response rate in patients with active brain metastases. In the HER2CLIMB trial, tucatinib reduced intracranial progression by 68% and improved OS (24.7 vs. 19.2 months) in patients with active brain metastases. Recent advances have increased median OS from approximately 20 months prior to trastuzumab to over 50 months with current therapies. Future research should focus on optimizing treatment sequencing, refining biomarker-driven approaches, and developing targeted strategies for brain metastases to further improve long-term survival outcomes.

Therapies targeting human epidermal growth factor receptor 2 (HER2) have substantially improved overall survival in patients with HER2-positive metastatic breast cancer. Approximately 31% of these patients develop brain metastases, representing a significant therapeutic challenge. This review classifies anti-HER2 therapies into three categories: monoclonal antibodies (MABs), antibody-drug conjugates (ADCs), and tyrosine kinase inhibitors (TKIs). The mechanisms of action and clinical impacts of these agents are examined, with particular attention to intracranial efficacy. The introduction of trastuzumab increased overall survival (OS) from 20.3 to 25.1 months compared to chemotherapy alone. The addition of pertuzumab further extended survival to 57.1 months, as demonstrated in the CLEOPATRA trial. Among ADCs, T-DM1 improved OS to 29.9 months versus 25.9 months in the EMILIA trial, while T-DXd extended OS to 52.6 months in DESTINY-Breast03. T-DXd also demonstrated notable intracranial activity, achieving a 64.9% objective response rate in patients with active brain metastases. In the HER2CLIMB trial, tucatinib reduced intracranial progression by 68% and improved OS (24.7 vs. 19.2 months) in patients with active brain metastases. Recent advances have increased median OS from approximately 20 months prior to trastuzumab to over 50 months with current therapies. Future research should focus on optimizing treatment sequencing, refining biomarker-driven approaches, and developing targeted strategies for brain metastases to further improve long-term survival outcomes.