In human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, taxane-based chemotherapy combined with anti-HER2 antibodies trastuzumab and pertuzumab (THP) has remained the first-line standard of care for more than 13 years, based on data from the phase III CLEOPATRA trial. Although THP has substantially improved outcomes in this aggressive subtype, real-world evidence indicates that approximately 30% of patients never receive second-line treatment. This high rate of first-to-second line attrition highlights a persistent gap in clinical care despite the availability of effective post-progression options, most notably trastuzumab deruxtecan (T-DXd), and the need to optimize upfront treatment strategies. Recent landmark studies are poised to redefine first-line management. The DESTINY-Breast09 trial demonstrated the superiority of first-line T-DXd plus pertuzumab over THP, while the PATINA and HER2CLIMB-05 trials reported clinically meaningful benefits from incorporating the cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib and the HER2 tyrosine kinase inhibitor (TKI) tucatinib, respectively, into first-line maintenance therapy. This review examines ongoing challenges in the management of HER2-positive metastatic breast cancer and summarizes the key findings from these practice-changing studies. PEER REVIEWED ARTICLE **Peer reviewers:** Dr Vérène Dougoud, Department of Oncology, HFR Hospital Fribourg, Switzerland Dr Andreas Hochstrasser, Thun Hospital, Thun, Switzerland One anonymous peer reviewer Received on March 25, 2025; accepted after peer review on May 19, 2026; published online on May 26, 2026.
# Introduction The phase III AMPLIFY trial established fixed-duration acalabrutinib plus venetoclax as an effective, all-oral, chemotherapy-free frontline therapy for chronic lymphocytic leukemia (CLL). We report the real-world use of this regimen in a patient with rapidly progressive _IGHV_-mutated CLL. # Case presentation A 46-year-old man with _IGHV_-mutated CLL without _TP53_ mutation/del(17p) initially managed with observation developed rapid disease progression characterized by lymphocytosis, anemia and thrombocytopenia. He received fixed-duration acalabrutinib (100 mg twice daily) and venetoclax (ramp-up to 400 mg once daily) according to the AMPLIFY regimen. The treatment was well tolerated, with no tumor lysis syndrome or treatment interruptions. Following the expected redistribution lymphocytosis after acalabrutinib initiation, lymphocyte counts rapidly normalized upon venetoclax ramp-up. Hemoglobin level and platelet counts improved progressively. # Conclusion This case demonstrates that fixed-duration acalabrutinib plus venetoclax is a highly effective, safe and logistically feasible frontline treatment for patients with _IGHV_-mutated CLL and aggressive disease kinetics, translating clinical trial efficacy into real-world practice. PEER REVIEWED ARTICLE **Peer reviewers:** Prof. Marcus Schittenhelm, HOCH Health Ostschweiz, Cantonal Hospital St.Gallen, St.Gallen, Switzerland Dr Guido Ghilardi, Oncology Institute of Southern Switzerland and Cantonal Hospital Bellinzona, Bellinzona, Switzerland Received on April 02, 2026; accepted after peer review on May 18, 2026; published online on May 25, 2026.
Oxidized phospholipids (OxPLs) are biologically active products of lipid peroxidation that accumulate in the tumor milieu as a consequence of oxidative stress, cell death and metabolic alterations. Recent data suggest that OxPLs are not merely by-products of oxidative injury but active mediators that influence multiple aspects of tumor biology. This review summarizes the current knowledge on the accumulation and (patho)physiological effects of OxPLs in cancer. Functionally, OxPLs promote epithelial-to-mesenchymal and endothelial-to-mesenchymal transition, angiogenesis, inflammatory signaling and reactivation of dormant cancer cells, thereby supporting tumor progression. Furthermore, oxidation of membrane phospholipids is a central mechanism of ferroptosis, a form of cell death driven by massive intracellular lipid peroxidation. Factors that define tumor sensitivity to ferroptosis include oncogenic mutations, tumor suppressor pathways and metabolic properties of the tumor microenvironment, such as lipid availability, lactate accumulation and glucose deprivation. Importantly, OxPLs and ferroptosis exert dual effects on the antitumor immune response: they can enhance immunity by promoting dendritic cell activation and cytokine-mediated ferroptotic elimination of tumor cells, but they can also suppress it by impairing effector T-cell function and promoting the recruitment of immunosuppressive myeloid cells, thereby facilitating immune escape. Thus, OxPLs emerge as pleiotropic regulators at the interface of oxidative stress, tumor progression, ferroptosis and immunity. Better understanding of the mechanistic role of OxPLs in tumor biology will be essential for the development of more effective ferroptosis-based and immunomodulatory anti-cancer therapies. PEER REVIEWED ARTICLE **Peer reviewers:** Prof. Corinne M. Spickett, School of Biosciences and Aston Institute for Membrane Excellence, Aston University, Birmingham, UK One anonymous peer reviewer Received on March 11, 2026; accepted after peer review on May 06, 2026; published online on May 15, 2026.
Multiple myeloma (MM) is a hematologic malignancy characterized by frequent relapses and ultimately acquired resistance to therapy across sequential lines of treatment. Nevertheless, treatment options are evolving rapidly, with the introduction of novel agents and immune-based therapies that deepen responses, prolong remission durations and improve survival as well as quality of life, thereby markedly improving patient outcomes. The current management of MM involves a multidrug-class strategy tailored by transplant eligibility, frailty, cytogenetic, clinical and molecular risk stratification, with quadruplet regimens set to become the standard of care in newly diagnosed MM (NDMM). These combinations include immunomodulatory drugs, proteasome inhibitors, anti-CD38 monoclonal antibodies and corticosteroids, and, in selected settings, alkylating agents, with this approach now being increasingly tailored to each individual patient. Additionally, novel treatment approaches, such as chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies, have gained regulatory approval in the relapsed/refractory setting and are now being integrated into earlier lines of therapy. This review summarizes recent clinical trial data and evolving therapeutic strategies in NDMM, including response-adapted and minimal residual disease (MRD)-guided approaches, regimens based on the anti-CD38 monoclonal antibodies daratumumab and isatuximab, the bispecific antibodies teclistamab, elranatamab and linvoseltamab, the antibody-drug conjugate belantamab mafodotin, the next-generation cereblon E3 ligase modulatory drug (CELMoD) iberdomide, as well as cytogenetic and molecular determinants of treatment outcomes. PEER REVIEWED ARTICLE **Peer reviewers:** Prof. Ji Hyun Lee, Division of Hematology-Oncology, Department of Internal Medicine, Dong-A University College of Medicine, Busan, Republic of Korea One anonymous peer reviewer Received on March 17, 2026; accepted after peer review on May 12, 2026; published online on May 19, 2026.
# Background Older adults account for a disproportionate burden of cancer-related morbidity and mortality; however, they are often underrepresented in clinical trials and may receive suboptimal or non-individualized care. To improve care for this population, we established a geriatric oncology service at a medium-sized regional hospital and launched the Prospective Registry for Older Patients with Cancer (PRO-PAC) to systematically collect clinical, functional and treatment-related data in this vulnerable population. # Methods In January 2024, a multidisciplinary geriatric oncology service was launched at Kantonsspital Baselland, starting with a 9-month test period to determine the feasibility of the concept. Patients aged ≥70 years with a G-8 score of ≤14/17 underwent a comprehensive geriatric assessment (CGA) by an oncologist, geriatrician and oncology nurse. All data were prospectively entered into the PRO-PAC registry. # Results Among 17 enrolled patients (median age, 79.4 ± 6.2 years), all presented with solid tumors, predominantly gastrointestinal and gynecological; most had locally advanced or metastatic disease. Functional impairments (mean Barthel Index, 57.3) and malnutrition (75%) were prevalent; cognitive impairment was observed in 12.5% and polypharmacy (≥5 medications) in 70.6% of patients. In the majority of cases (58.8%), CGA findings led to suggested treatment adaptations, including changes in the therapy regimen, dose reductions or supportive care measures. Both patients and clinicians valued the assessment process and the recommended treatment adaptations. # Conclusions Our preliminary experience demonstrates the feasibility of implementing geriatric oncology service in a medium-sized hospital. Integrating CGA into routine care required additional resources but enabled more informed, patient-centered decision-making. High prevalence of geriatric syndromes underscores the importance of individualized approaches in older cancer patients and supports the clinical value of such service. Data collection in the PRO-PAC registry was successful. As the registry expands, future analyses will explore associations between CGA parameters and clinical outcomes to optimize oncological care for the aging population. PEER REVIEWED ARTICLE **Peer reviewers:** Prof. Andreas Trojan, Department of Oncology, See-Spital, Horgen, Switzerland Dr Wiebke Rösler, Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland Received on February 20, 2026; accepted after peer review on May 13, 2026; published online on May 22, 2026.
Endometrial cancer is the most prevalent gynecologic malignancy in developed countries, with an increasing incidence driven primarily by rising obesity and aging populations. While survival rates are high, particularly for early-stage, low-grade disease, many endometrial cancer survivors experience significant menopausal symptoms due to the definitive surgical treatments. Hormone replacement therapy (HRT) remains the most effective treatment for vasomotor and genitourinary symptoms of menopause; however, its use in women with endometrial cancer has been met with caution. This review synthesizes the current evidence, evaluates risk stratification models and offers a practical, patient-centered approach to the use of HRT in endometrial cancer survivors. PEER REVIEWED ARTICLE **Peer reviewers:** Prof. Andreas Günthert, Gynecological Tumor Center St. Anna, Lucerne, Switzerland Dr Eleftherios Pierre Samartzis, Gynecological Tumor Center, University Hospital Zurich, Zurich, Switzerland Received on December 15, 2025; accepted after peer review on February 23, 2026; published online on February 25, 2026.
Antibody-drug conjugates (ADCs) have redefined the therapeutic paradigm of metastatic breast cancer by combining targeted antibody specificity with potent cytotoxic payloads. The regulatory approvals of sacituzumab govitecan (SG), trastuzumab deruxtecan (T-DXd) and datopotamab deruxtecan (Dato-DXd) have expanded treatment options for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative and triple-negative breast cancer. However, as more patients become exposed to multiple ADCs during their disease course, optimal sequencing strategies remain undefined. This review discusses the evolving role of ADCs in the management of metastatic breast cancer and examines emerging evidence on their sequential use across different molecular subtypes. It summarizes findings from real-world studies and retrospective analyses that evaluate clinical outcomes, safety profiles and potential mechanisms of cross-resistance when ADCs are used sequentially. The biological determinants of response and resistance mechanisms are explored. Furthermore, this article outlines current guideline recommendations and highlights ongoing clinical and translational studies investigating sequencing approaches and biomarker-driven strategies. Collectively, these studies support the development of an individualized framework for ADC sequencing in metastatic breast cancer, bridging the current clinical practice with the emerging precision oncology paradigm. PEER REVIEWED ARTICLE **Peer reviewers:** Dr Jose Luis Sandoval, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland One anonymous peer reviewer Received on January 05, 2026; accepted after peer review on February 09, 2026; published online on February 16, 2026.
A small proportion of patients with acute promyelocytic leukemia (APL) harbor variant chromosomal translocations that lead to fusion of *RARA* to one of several alternative partner genes. The most frequently reported of variant is the t(11;17)(q23;q21), which generates the fusion of the zinc finger gene *ZBTB16* (formerly PLZF) to the *RARA* locus (*ZBTB16::RARA* fusion). This APL subtype is typically resistant to standard APL-directed therapies and most patients with this translocation relapse within one year with limited subsequent treatment options. Here, we report on a patient with *ZBTB16::RARA* APL who achieved durable molecular complete remission lasting more than two years after high-dose chemotherapy with busulfan and cyclophosphamide followed by autologous stem cell transplantation. This therapeutic approach has not previously been described for this rare APL variant and may represent a promising consolidation strategy in selected patients. PEER REVIEWED ARTICLE **Peer reviewers:** Prof. Dr Stefan Balabanov, Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland Prof. Dr Alicia Rovó, Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland Received on January 19, 2026; accepted after peer review on February 19, 2026; published online on February 23, 2026.
Richter’s transformation to diffuse large B-cell lymphoma (DLBCL) represents a rare and aggressive malignancy, typically associated with poor prognosis and limited therapeutic options. We report the case of a 72-year-old patient with rapidly progressing, high-tumor burden disease after several intensive chemotherapy regimens. The patient subsequently received chimeric antigen receptor (CAR) T-cell therapy, achieving a complete response just one month after infusion, which was sustained at the 18-month follow-up. This positive outcome highlights the potential of CAR T cells in refractory, high-risk rare cases that are often excluded from clinical trials. In addition, we describe a second case involving a 48-year-old patient with post-transplant lymphoproliferative disorder (PTLD) after solid organ transplantation complicated by central nervous system (CNS) involvement, who similarly attained complete remission (CR) following CAR T-cell therapy. Together, these cases underscore the efficacy and versatility of CAR T-cell therapy in rare and challenging DLBCL presentations, providing further clinical evidence to support its use in high-risk patient populations. PEER REVIEWED ARTICLE **Peer reviewers:** Prof. Dr Dr Dominik Schneidawind, University Hospital Zurich, Zurich, Switzerland One anonymous peer reviewer Received on November 10, 2025; accepted after peer review on December 05, 2025; published on December 08, 2025.
The diagnosis of myelodysplastic neoplasms (MDS) traditionally relies on cytomorphological assessment of peripheral blood (PB) and bone marrow (BM). Despite recent shifts toward molecular testing and next-generation sequencing, blast percentage and dysplasia remain integral to the initial work-up. Morphology provides immediate availability and cost-effectiveness but is hindered by interobserver variability, lack of standardization and declining training in classical hematology. These factors may complicate the differentiation of MDS from non-clonal cytopenias or therapy-related changes. Technical quality of BM sampling and processing is crucial, as inadequate core length, improper fixation or artifacts may obscure interpretation. Digital morphology and artificial intelligence (AI) are reshaping hematology by reducing subjectivity, improving reproducibility and enabling remote consultation, training and archiving. Although automated analyzers demonstrate high accuracy for common cell types, expert oversight remains essential, especially for rare or pathological cells. AI and machine learning (ML) extend across diagnostic modalities, from detecting dysplasia in PB and BM smears to automating flow cytometry gating, karyotyping and variant analysis. These approaches can differentiate MDS from aplastic anemia or acute myeloid leukemia with high accuracy, although generalizability is limited by small datasets, technical variability and insufficient external validation. Ethical, regulatory and educational challenges persist, underscoring the need for explainable models and clinician AI literacy. PEER REVIEWED ARTICLE **Peer reviewers:** Prof. Dr Ulrich Germing, Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany Prof. Dr Alexandar Tzankov, Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland Received on September 29, 2025; accepted after peer review on November 14, 2025; published online on November 25, 2025.
Radioligand therapy (RLT) is a targeted molecular approach that couples the specificity of receptor-mediated binding with the cytotoxic effects of radionuclide emission to achieve selective tumor irradiation while limiting damage to healthy tissues. This review summarizes the key recent updates in RLT, highlighting the major clinical advances in prostate cancer and gastroenteropancreatic neuroendocrine tumors (GEP-NETs). In GEP-NETs, the α-emitting compound [212Pb]Pb-DOTAMTATE demonstrated durable responses and a favorable safety profile in patients who had previously [177Lu]Lu-DOTATATE-based RLT, marking an important step toward next-generation α-particle therapies. In prostate cancer, data from large randomized trials further defined the role of [177Lu]Lu-PSMA-617 across disease settings, including comparisons with docetaxel, combination therapy with androgen deprivation and androgen receptor pathway inhibitors (ARPI) and neoadjuvant use before stereotactic body radiotherapy. Early phase studies have investigated novel therapeutic concepts, such as α–β emitter combinations, poly(ADP-ribose) polymerase (PARP) inhibitor synergy and emerging non-PSMA targets such as ACP3. Collectively, these findings reflect a rapidly expanding field, where improved ligand design, new isotopes and combinations are driving RLT toward broader clinical integration and more personalized treatment strategies. PEER REVIEWED ARTICLE **Peer reviewers:** Prof. Dr Klaus Strobel, Department of Radiology and Nuclear Medicine, Luzerner Kantonsspital, University Teaching and Research Hospital, University of Lucerne, Lucerne, Switzerland. Dr Riccardo Laudicella, Nuclear Medicine, Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, Messina University, Messina, Italy. Received on October 31, 2025; accepted after peer review on November 20, 2025; published online November 29, 2025.
Endocrine therapy remains a cornerstone treatment for patients with hormone receptor-positive breast cancer. However, its benefits are often undermined by treatment-related adverse events, including vasomotor symptoms (VMS) such as hot flashes and night sweats. These symptoms can substantially impair quality of life and contribute to poor treatment adherence, thereby reducing the effectiveness of endocrine therapy and potentially increasing the risk of disease recurrence. While hormone replacement therapy is effective for managing postmenopausal hot flashes in the general population, it is contraindicated in women receiving endocrine, essentially an anti-estrogen, breast cancer treatment. Therefore, safe and effective non-hormonal strategies are required. Traditional pharmaceutical options, such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, gabapentin and clonidine, provide modest benefit but are often limited by their own side effects or drug-drug interactions with endocrine therapies. More recently, targeted approaches using neurokinin receptor antagonists, including fezolinetant and elinzanetant, have shown promise in reducing the frequency and severity of VMS. This review highlights the rationale, evidence and clinical potential of neurokinin receptor antagonists as emerging non-hormonal options for managing breast cancer-related VMS. PEER REVIEWED ARTICLE **Peer reviewers:** PD Dr Mattea Reinisch, Interdisciplinary Breast Unit, University Hospital Mannheim, Mannheim, Germany. Dr Anton Oseledchyk, Department of Biomedicine and Division of Oncology, Basel University Hospital and University of Basel, Basel, Switzerland. Received on September 15, 2025; accepted after peer review on December 05, 2025; published online on December 08, 2025.
The cancer treatment landscape is rapidly evolving, with several practice-changing studies in breast cancer recently presented at major international oncology congresses. Targeted therapy is gaining momentum as a first-line treatment of metastatic breast cancer. Circulating tumor DNA (ctDNA) already informs treatment selection in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. The landmark SERENA-6 and INAVO120 studies investigated selective inhibitors of estrogen receptor and phosphoinositide 3-kinase (PI3K), respectively, each demonstrating clinically meaningful benefits. Meanwhile, antibody-drug conjugates are poised to redefine the first-line strategy in HER2-positive and triple-negative metastatic breast cancer, based on compelling findings from the DESTINY-Breast09, ASCENT-04/KEYNOTE-D19, ASCENT-03 and TROPION-Breast02 trials. This review summarizes the key findings from these pivotal studies and their implication for future clinical practice. PEER REVIEWED ARTICLE **Peer reviewers:** Prof. Dr Rupert Bartsch, Division of Oncology, Medical University of Vienna, Vienna, Austria Dr Ruben Bill, Department of Medical Oncology, Bern University Hospital, Bern, Switzerland PD Dr Cvetka Grašič Kuhar, Institute of Oncology Ljubljana, Slovenija PD Dr Constanze Elfgen, Breast-Center Zurich, Zurich, Switzerland Received on October 21, 2025; accepted after peer review on November 24, 2025; published online on November 28, 2025.
Anti-CD19 chimeric antigen receptor (CAR) T-cell immunotherapy has emerged as the new standard of care as a second-line treatment in refractory or early relapsing (R/R) large B-cell lymphoma (LBCL) patients. Given the notable incidence of LBCL in Switzerland, managing R/R disease remains a significant clinical challenge, especially in patients who do not respond to standard frontline chemoimmunotherapy. This review explores pivotal clinical trials that have driven the shift toward the earlier use of CAR T-cell immunotherapy in LBCL, highlighting its potential to improve clinical outcomes in primary refractory disease. Particular focus is given to the evolving role of CAR T-cell immunotherapy. Promising data suggest that its use in upfront lines of therapies might result in better disease control, even in high-risk, chemoresistant LBCL patients. Finally, we will discuss potential biological factors at the basis of the improved CAR T-cell activities observed when used in earlier lines of therapies. As CAR T-cell immunotherapies continue to be integrated into clinical practice, ongoing research and future trial data will be crucial for refining therapeutic protocols and optimizing patient outcomes. PEER REVIEWED ARTICLE **Peer reviewers:** Three anonymous peer reviewers Received on April 25, 2025; accepted after peer review on August 29, 2025; published online on September 26, 2025.
Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein that is overexpressed in prostate cancer cells, with limited expression in benign and extraprostatic tissues. Based on these characteristics, several low-molecular-weight PSMA inhibitor radioligands have been developed for disease management strategies that integrate both therapeutic and diagnostic applications, collectively termed theranostics. Currently, four common diagnostic radiotracers include ^68^Ga-PSMA-11, ^18^F-DCFPyL, ^18^F-radiohybrid (rh)PSMA-7.3 and ^18^F-PSMA-1007, with the first three being approved by the U.S. Food and Drug Administration (FDA). Additionally, ^68^Ga-PSMA-11 and ^18^F-DCFPyL are also approved by the European Medicines Agency (EMA), while ^18^F-PSMA-1007 is approved on a country-by-country basis. PSMA-targeted radionuclide therapy is also a promising therapeutic option for men with prostate cancer. To date, ^177^Lu-PSMA-617 is the only PSMA-targeted radioligand therapy approved by both the FDA and EMA for clinical use. Emerging α-emitting therapies such as ^225^Ac-PSMA-617 are currently under clinical investigation and may provide additional benefit in patients with advanced or resistant disease. This review article provides a brief overview of available PSMA ligands for the diagnosis and treatment of advanced prostate cancer. PEER REVIEWED ARTICLE Received on June 06, 2025; accepted after peer review on October 13, 2025; published on October 15, 2025. **Peer reviewers:** Prof. Dr Oliver Sartor, Transformational Prostate Cancer Research Center, East Jefferson General Hospital, Metairie, Louisiana, USA One anonymous peer reviewer
Non-Hodgkin's lymphoma (NHL) is a generic name for a diverse group of malignancies arising from lymphocytes and primarily affecting the lymph nodes, but also involving other organs. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a groundbreaking treatment for patients with NHL, offering hope for those who have relapsed or are refractory to conventional therapies. However, due to the risk of toxicities such as cytokine release syndrome and neurotoxicity, the efficacy and safety of CAR T-cell therapy are highly dependent on patient selection criteria. This article outlines the most important considerations that clinicians need to make when evaluating candidates for CAR T-cell therapy. Key parameters for the optimal patient selection scale were categorized into four domains: disease biology, tumor burden and microenvironment, patient factors and risk mitigation. A 100-point scoring scale was created and patients were stratified into three prognostic groups: ideal candidates (≥70 points), conditional approval (40–69 points) and non-recommended (<40 points). By integrating tumor-, host- and risk-mitigation-specific parameters, the novel score provides a practical and systematic approach to clinical decision-making in the field of cellular immunotherapy for NHL. Received on July 07, 2025; accepted after peer review on October 02, 2025; published on October 10, 2025. PEER REVIEWED ARTICLE Peer reviewers: Two anonymous peer reviewers
Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer constitutes the most prevalent subtype of metastatic breast cancer and remains an incurable condition marked by eventual resistance to endocrine therapy (ET). While recent advances including the integration of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors and other targeted agents, such as poly (ADP-ribose) polymerase (PARP) inhibitors, oral selective estrogen receptor degraders (SERDs) and antibody–drug conjugates, have expanded treatment options, endocrine resistance continues to present a significant clinical challenge. This review outlines the evolving therapeutic landscape in HR+/HER2– advanced breast cancer, with a particular emphasis on the PI3K/AKT/PTEN signaling pathway and its role in mediating endocrine resistance. We provide a comprehensive overview of capivasertib, an oral selective pan-AKT inhibitor that demonstrated antitumor efficacy in preclinical and clinical studies, particularly in tumors harboring PIK3CA, AKT1 or PTEN alterations. The review details the design and clinical outcomes of the pivotal CAPItello-291 trial, which established the clinical benefit of combining capivasertib with fulvestrant in patients with ET-resistant HR+/HER2– advanced breast cancer. We also discuss the biological rationale, clinical positioning and regulatory approval of capivasertib, situating it within current treatment guidelines. Together, these data emphasize the importance of biomarker-driven therapy for optimizing patient selection and therapeutic strategies in the increasingly personalized treatment landscape for HR+/HER2– advanced breast cancer. PEER REVIEWED ARTICLE Peer reviewers: Dr Mira Sofie Witek, Clinical Department of Internal Medicine III, Hematology and Internal Oncology, University Hospital Wiener Neustadt One anonymous peer reviewer Received on June 11, 2025; accepted after peer review on October 03, 2025; published online on October 06, 2025.
The lung cancer treatment landscape is rapidly evolving, with advances extending across non-small cell lung cancer (NSCLC), pleural mesothelioma and small cell lung cancer (SCLC). Immune checkpoint inhibitors (ICIs), targeted therapies and novel combination regimens offer new hope for patients with thoracic malignancies and are reshaping standards of care. At the European Lung Cancer Congress (ELCC 2025), the Swiss Cancer Institute (formerly SAKK) presented its research across disease subtypes, including the final results from the phase II trial SAKK 16/14 investigating perioperative durvalumab in combination with neoadjuvant chemotherapy in patients with resectable stage IIIA(N2) NSCLC and findings from the phase II trial SAKK 17/18 ORIGIN investigating gemcitabine combined with atezolizumab in patients with pleural mesothelioma. The Swiss Cancer Institute is also contributing to several collaborative group trials, including ETOP AMAZE-lung investigating amivantamab plus lazertinib and bevacizumab in EGFR-mutant NSCLC post-osimertinib, ETOP 25-23 ADOPT-lung evaluating neo-adjuvant versus peri-operative durvalumab in patients with resectable NSCLC and a real-world analysis of extensive-stage (ES)-SCLC molecular subtypes and clinical outcomes. This article summarizes key data from these relevant clinical studies. Received on June 18, 2025; accepted after peer review on October 05, 2025; published on October 13, 2025. PEER REVIEWED ARTICLE **Peer reviewers:** Prof. Daniel Betticher, Clinic of Medical Oncology, Cantonal Hospital of Fribourg, Fribourg, Switzerland One anonymous peer reviewer
