Cancer Treat. Rev. [JOURNAL]
Sun
200 papers
A systematic review of phase I trials in patients with ovarian cancer.
Pavone G, Martorana F, Ricco V … +4 more , Ciliberti EA, Nerone M, Sessa C, Colombo I
Cancer Treat Rev · 2025 Sep · PMID 40582156 · Publisher ↗
BACKGROUND: Ovarian cancer (OC) is the leading cause of death among gynecological malignancies, with limited treatment options for advanced and platinum-resistant disease. This systematic review analyzes phase I trials t...
BACKGROUND: Ovarian cancer (OC) is the leading cause of death among gynecological malignancies, with limited treatment options for advanced and platinum-resistant disease. This systematic review analyzes phase I trials to assess recent therapeutic advancements. METHODS: We performed a systematic review of phase I trials in OC, published between 2012 and 2023, retrieving data on trial characteristics and outcomes. Studies were classified according to the tested treatment strategies into chemotherapy-only (CO), chemotherapy + non-chemotherapy agents (CNC) and chemotherapy-free (CF). RESULTS: 78 trials were included, with more than 50 % of them published in the last four years. Overall, chemotherapy and immunotherapy were the most investigated agents. Fourteen trials (17.9 %) evaluated a CO strategy, 42 (53.8 %) a CNC combination and 22 (28.2 %) a CF therapy. Dose-limiting toxicities and toxic deaths were observed in 71 % and 100 % of CO studies, in 45.2 % and 21 % of CNC trials and in 37.4 % and 13.6 % of CF trials, respectively. CNC regimens outperformed the other treatment types in terms of efficacy outcomes, including overall response rate (11.5 % CO; 32.2 % CNC; 25.5 % CF), clinical benefit rate (40 % CO; 62 % CNC; 52 % CF) and median progression free survival (mPFS 5.9 months CO; 6.45 months CNC; 4.85 months CF). Trials enrolling platinum resistant or agnostic patients displayed worse clinical outcomes. CONCLUSIONS: In the last years, there has been an increasing number of phase 1 trials assessing new agents and new combinations in patients with OC. Chemotherapy-free strategies display a more favorable safety profile, while regimens combining CNC agents seem to be more effective compared to CO approaches.
Immunocytokines in cancer treatment: A systematic review.
Agliardi S, Veronese C, Panzeri F … +17 more , Palazzini S, Guarnieri G, Loiacono S, Martinelli V, Potenza AM, Sbraga E, Rissotto E, Inglese E, Tosi F, Villa F, Patelli G, Monti L, Pani A, Danesi R, Fornasari D, Siena S, Sartore-Bianchi A
Cancer Treat Rev · 2025 Sep · PMID 40554920 · Publisher ↗
INTRODUCTION: Immunocytokines are an emerging class of antibody-cytokine fusion proteins combining the specificity of monoclonal antibodies with the potent immunostimulatory effects of cytokines, potentially enhancing th...
INTRODUCTION: Immunocytokines are an emerging class of antibody-cytokine fusion proteins combining the specificity of monoclonal antibodies with the potent immunostimulatory effects of cytokines, potentially enhancing the anti-tumor immune response while reducing systemic toxicity. METHODS: We conducted a systematic review following the PRISMA guidelines. We performed a comprehensive literature search using PubMed and ClinicalTrials.gov databases. The search strategy included the terms "immunocytokine", "cytokine", "tumor", and "cancer". Filters were applied to retrieve only peer-reviewed articles and clinical trials. RESULTS: 25 publications were retrieved: 15 were Phase I studies; 2 Phase I/II, and 8 Phase II. Regarding ongoing clinical trials, 62 studies were included: 30 were Phase I studies, 2 Phase III, and the remaining 30 were either Phase II (n = 13) or Phase I/II (n = 17). In 50/62 trials, the primary and co-primary outcomes included safety measures, such as adverse effects, dose-limiting toxicities, and maximum tolerated dose. In both studies from literature and ongoing clinical trials, the most common target was extra-domain B (EDB) of fibronectin, and the most investigated type of cancer was melanoma. While all published studies focused on solid tumors, several ongoing trials include hematologic malignancies. CONCLUSIONS: Research interest in immunocytokines as a potential cancer treatment is increasing, although only limited data are currently available. Several trials, mainly in the early phase, are ongoing, paving the way for a possible broader clinical application of this class of immunotherapeutics.
Surgical tumor volume reduction in patients with brain metastases: A systematic review and meta-analysis.
Stumpo V, Carretta A, Bellomo J … +13 more , Padevit L, Staartjes V, Maldaner N, Coker P, Fierstra J, Weller M, Le Rhun E, Czabanka M, Bozinov O, Regli L, Neidert MC, Serra C, Voglis S
Cancer Treat Rev · 2025 Sep · PMID 40554919 · Publisher ↗
BACKGROUND: Microsurgical resection of brain metastases (BM) has traditionally been a mainstay of local control for large or symptomatic lesions. Maximal tumor burden reduction remains controversial in the multidisciplin...
BACKGROUND: Microsurgical resection of brain metastases (BM) has traditionally been a mainstay of local control for large or symptomatic lesions. Maximal tumor burden reduction remains controversial in the multidisciplinary management of BM patients and needs to be re-evaluated in view of new systemic treatment options. We conducted a systematic review and meta-analysis to evaluate the role of extent of resection (EOR)/residual volume (RV) for progression-free (PFS) and overall survival (OS) in patients with BM. METHODS: A systematic review was performed according to PRISMA guidelines and included studies' quality was assessed with the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. Study characteristics were tabulated and critically reviewed. Results from Cox-regression models and log-rank tests for the association of gross total resection (GTR) versus subtotal resection (STR) with PFS and OS were extracted to perform separate random-effects meta-analyses. RESULTS: Thirty-nine articles were included, all of them being retrospective and all but 3 monocentric. Most studies included BM from heterogenous primary tumors, with 9 focusing on BM from a single primary. Systemic therapies were variably reported and only 2 studies reported on the use of steroids. Twenty-one studies showed a significant association of EOR/RV with improved OS. Meta-analysis of studies reporting multivariable Cox-regression models (n = 11) showed a significant association of GTR with longer OS (HR 0.67, 95 %CI 0.56-0.81, p < 0.001). CONCLUSION: Although in several studies higher EOR/lower RV was associated with improved OS, evidence consists of heterogeneous cohorts and rarely includes primary tumor-specific systemic therapies or relevant confounding covariates. New studies are needed to elucidate the role of microsurgical tumor burden reduction in BM patients in the era of targeted or immune modulatory therapies.
Overcoming Resistance to CDK4/6 inhibitors in Hormone Receptor positive, HER2 negative breast cancer: Innovative Combinations and Emerging Strategies.
Giugliano F, De Angelis C, Pistilli B … +10 more , Viale G, Bianchini G, Giuliano M, Malorni L, Taurelli Salimbeni B, Esposito A, Giordano A, Yap TA, Curigliano G, Criscitiello C
Cancer Treat Rev · 2025 Sep · PMID 40544690 · Publisher ↗
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) improve outcomes patients affected by metastatic and early-stage hormone receptor-positive, HER2-negative breast cancer. However...
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) improve outcomes patients affected by metastatic and early-stage hormone receptor-positive, HER2-negative breast cancer. However, approximately 20% of these tumors exhibit intrinsic resistance to such therapies, and most develop acquired resistance mechanisms that drive progression. Biomarker analyses of biological samples from patients treated with CDK4/6i plus ET have identified potential targets for therapeutic combinations. In this review, we discuss the mechanisms of action and resistance to CDK4/6i, providing a comprehensive overview of emerging efficacy and safety data, biomarker-driven strategies, and ongoing clinical trials. Finally, we delineate key research priorities aimed at guiding the development of innovative therapeutic combinations.
Ovarian escape in premenopausal breast cancer: Challenges and strategies for optimizing hormone suppression.
Luo L, Zhang Y, Zhang L … +4 more , Yang S, Zhou T, Luo K, Liu S
Cancer Treat Rev · 2025 Sep · PMID 40543109 · Publisher ↗
Ovarian function suppression (OFS) is extensively acknowledged for its efficacy and benefits in the management of breast cancer among premenopausal women. While gonadotropin-releasing hormone agonists (GnRHa) serve as th...
Ovarian function suppression (OFS) is extensively acknowledged for its efficacy and benefits in the management of breast cancer among premenopausal women. While gonadotropin-releasing hormone agonists (GnRHa) serve as the fundamental component of OFS, a subset of patients experience incomplete estrogen suppression, leading to potential treatment failure and adverse outcomes. This review systematically examines ovarian escape (OE) during GnRHa treatment in premenopausal women with hormone receptor-positive (HR+) breast cancer and explores potential risk factors along with the underlying mechanisms. Discrepancies in defining menopausal status and assay variability complicate OE diagnosis; however, early detection and intervention can mitigate the risk of treatment failure. Current guidelines lack standardized guidelines for hormone monitoring, underscoring the need for personalized strategies to optimize OFS efficacy and mitigate risks. Further research is warranted to elucidate OE mechanisms and refine therapeutic approaches. By proposing evidence-based management strategies, this work advances personalized OFS approaches tailored to high-risk populations.
PREDICTIVE BRCA GENETIC TESTING IN ITALIAN PATIENTS WITH BREAST CANCER: A POSITION PAPER OF ITALIAN SCIENTIFIC SOCIETIES [Italian Association of Medical Oncology(AIOM); Italian Association of Radiotherapy and Clinical Oncology (AIRO); Italian National Association of Breast Surgeons (ANISC); Italian Society of Pathological Anatomy and Diagnostic Cytology (SIAPeC-IAP); Italian Society of Surgical Oncology (SICO); Italian Society of Human Genetic (SIGU); Italian Society of General Practice (SIMG); Italian Society of Medical and Interventional Radiology (SIRM)].
Cortesi L, Miglietta F, Arecco L … +30 more , Bernardi D, Biganzoli L, Del Mastro L, Dieci MV, Foglietta J, Fortunato L, Franco P, Cordisco EL, Mantellini P, Marchio' C, Meduri B, Micallo G, Musolino A, Salvetti A, Turchetti D, Zambelli A, Angiolini C, Cinieri S, Conte PF, Curigliano G, Dessena M, Fabi A, Leonardi MC, Meattini I, Montemezzi S, Puglisi F, Sapino A, Taffurelli M, Cinquini M, Gori S
Cancer Treat Rev · 2025 Sep · PMID 40543108 · Publisher ↗
The introduction of Poly (ADP-ribose) Polymerase (PARP) inhibitors in both metastatic and early-stage breast cancer (BC) treatment has led to the emergence of Mainstreaming Cancer Genetics (MCG) as a new approach to gene...
The introduction of Poly (ADP-ribose) Polymerase (PARP) inhibitors in both metastatic and early-stage breast cancer (BC) treatment has led to the emergence of Mainstreaming Cancer Genetics (MCG) as a new approach to genetic counselling, predictive of therapy outcomes. Therefore, the BRCA testing criteria for therapeutic purposes require further implementation. This position paper outlines the Italian indications for predictive genetic testing, approved by a multidisciplinary Expert Panel representing major scientific societies involved in BC treatment in Italy. We utilized the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, and framed clinical questions as population, intervention, comparison and outcome (PICO). The final recommendations were determined through a voting process, covering key topics such as eligibility criteria for onco-genetic counselling, the role of contralateral prophylactic mastectomy (CPM) in patients harboring BRCA1/2 germline pathogenic variants (gPV), and the positioning of predictive BRCA1/2 test. As results, the Expert Panel defined three distinct patient groups eligible for onco-genetic counselling, based on the a priori likelihood of carrying a gPV and the purpose of testing (predictive vs preventive). A conditional recommendation in favor of CPM in patients with a history of surgically treated BC and a BRCA gPV was suggested. Finally, a multidisciplinary pathway for BRCA testing was proposed, for patients with triple negative and hormone receptor-positive (HR+)/HER2-negative (HER2-) BC. In conclusion, the predictive BRCA testing inside the onco-genetic framework marks an important step-forward in BC management. However, the integration of somatic testing, digital pathology, and artificial intelligence-driven models could refine patient selection for tailored treatments.
Advancements in liquid biopsy for breast Cancer: Molecular biomarkers and clinical applications.
Qiu P, Yu X, Zheng F … +9 more , Gu X, Huang Q, Qin K, Hu Y, Liu B, Xu T, Zhang T, Chen G, Liu Y
Cancer Treat Rev · 2025 Sep · PMID 40540857 · Publisher ↗
Breast cancer is characterized by significant molecular heterogeneity; therefore, there are distinct clinical features, treatment modalities, and prognostic outcomes across its various molecular subtypes. In the era of p...
Breast cancer is characterized by significant molecular heterogeneity; therefore, there are distinct clinical features, treatment modalities, and prognostic outcomes across its various molecular subtypes. In the era of precision medicine, liquid biopsy has emerged as a convenient and minimally invasive technique capable of dynamically representing the comprehensive tumor gene spectrum. This review systematically elaborates the clinical value of liquid biopsy as a breakthrough tool for precision diagnosis and treatment in breast cancer through dynamic detection of key biomarkers, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and non-coding RNA (ncRNA). Specific genetic mutations and methylation signatures in ctDNA can be applied to early breast cancer screening, minimal residual disease monitoring, and tracking drug resistance mechanisms. CTCs enumeration (≥1/7.5 mL in early-stage cancer or ≥ 5/7.5 mL in metastatic cancer) and PD-L1 expression levels demonstrate direct correlations with prognostic stratification and the efficacy of immunotherapy. As the specificity and sensitivity of liquid biopsy continue to improve, personalized treatment strategies, informed by biomarker analysis and targeted precision therapies, have unveiled new avenues of hope for patients with breast cancer. However, several challenges persist in the practical application of liquid biopsy. Despite persistent challenges, such as insufficient standardization and difficulties in resolving low-abundance variants, future advancements should focus on multi-omics integration and AI-driven technological breakthroughs to overcome bottlenecks in clinical translation. This review summarizes cutting-edge liquid biopsy technologies for identifying clinically significant molecular biomarkers, focusing on discussing critical challenges in the strategies to advance precision oncology applications for optimized treatment guidance and disease surveillance in breast cancer.
Clearer Horizons: The latest advances in clear cell ovarian cancer treatment.
Blanc-Durand F, Ngoi N, Lim D … +2 more , Ray-Coquard I, Tan DS
Cancer Treat Rev · 2025 Jul · PMID 40517636 · Publisher ↗
This review aims to consolidate the current understanding of Clear Cell Ovarian Carcinoma (CCOC), a rare yet distinct subtype of epithelial ovarian cancer. CCOC exhibits unique epidemiological, clinical and molecular fea...
This review aims to consolidate the current understanding of Clear Cell Ovarian Carcinoma (CCOC), a rare yet distinct subtype of epithelial ovarian cancer. CCOC exhibits unique epidemiological, clinical and molecular features, being one of the most frequent subtypes in East Asia, often diagnosed at an early stage and frequently affecting younger women. Its hallmark characteristics include high resistance to conventional chemotherapy, poor prognosis in advanced stage and a molecular profile distinct from high-grade serous histotype. Specifically, CCOC is characterized by a low prevalence of TP53 mutations, BRCA1/2 mutations and homologous-recombination deficiency, but a high frequency of ARID1A, along with other SWI/SNF alterations, and PIK3CA mutations, both of which represent promising therapeutic targets. Despite the absence of validated therapies for CCOC so far, significant advancements in preclinical research and emerging clinical strategies including immunotherapy combinations offer hope for improved outcomes. Given the rarity of this cancer type, collaborative research and global partnerships have enabled robust studies and the implementation of trials with innovative personalized therapeutic approaches. The objective of this report is to explore the epidemiology, clinical and molecular characteristics, current standard of care and evolving therapeutic strategies for CCOC patients. It will not only highlight the progress made so far, but most importantly identifies critical research priorities to optimizing patient outcomes.
Long and short-term efficacy and safety comparison of nab-paclitaxel versus paclitaxel combined with trastuzumab and pertuzumab for neoadjuvant treatment of HER2-positive breast cancer: A systematic review and meta-analysis.
Yuan Y, Long X, Wei M … +3 more , Chen L, Zhang J, Liu X
Cancer Treat Rev · 2025 Jul · PMID 40493995 · Publisher ↗
INTRODUCTION: Direct comparisons between nab-paclitaxel and solvent-based taxanes are scarce, with inconsistent results from mostly retrospective studies. High-level evidence comparing their efficacy in HER2-positive bre...
INTRODUCTION: Direct comparisons between nab-paclitaxel and solvent-based taxanes are scarce, with inconsistent results from mostly retrospective studies. High-level evidence comparing their efficacy in HER2-positive breast cancer remains lacking. Our study represents the first systematic review and meta-analysis to directly compare the long-term and short-term efficacy and safety of nab-paclitaxel versus solvent-based paclitaxel in combination with trastuzumab and pertuzumab for neoadjuvant treatment of HER2-positive breast cancer. METHODS: We performed a comprehensive literature search in PubMed, Embase, the Cochrane Library, CNKI, Wan Fang, and VIP databases to identify relevant studies published up to February 10, 2025. The search focused on studies involving patients with HER2-positive breast cancer who had not undergone prior treatments for their condition. These studies compared neoadjuvant therapies using either nab-paclitaxel-based chemotherapy (Nab-p arm) or solvent-based paclitaxel-based chemotherapy (Sb-p arm), both combined with pertuzumab and trastuzumab. The primary outcomes measured were event-free survival, disease-free survival, overall survival, and total pathological complete response. Secondary outcomes included objective response rate and adverse events. The quality of evidence was assessed using the GRADE methodology. RESULTS: A total of six studies, including 3 RCTs, 1 prospective cohort study and 2 real-world studies, involving 1556 patients were included. The Nab-p arm demonstrated numerically more favorable EFS, DFS compared to the Sb-p arm. There was no significant difference in OS between the Nab-p arm and the Sb-p arm. The Nab-p arm showed significant improvements in pCR (RR: 1.18, 95 % CI: 1.08-1.29, p < 0.001), pCR (with only RCTs) (RR: 1.13, 95 % CI: 1.03-1.24, p = 0.009), and ORR (RR: 1.30, 95 % CI: 1.07-1.57, p = 0.007) compared to the Sb-p arm. The Nab-p arm showed a lower grade III/IV diarrhea rate (RR: 0.59, 95 % CI: 0.42-0.83, p = 0.003), grade III/IV thrombocytopenia rate (RR: 0.46, 95 % CI: 0.24-0.89, p = 0.02), grade I/II allergic reactions rate (RR: 0.60, 95 % CI: 0.46-0.78, p < 0.001) and grade III/IV allergic reactions rate (RR: 0.33, 95 % CI: 0.14-0.82, p = 0.02), compared to the Sb-p arm. The Nab-p arm showed a higher grade I/II neuropathy rate (RR: 1.21, 95 % CI: 1.12-1.30, p < 0.001) and grade III/IV neuropathy rate (RR: 2.61, 95 % CI: 1.23-5.52, p = 0.001), compared to the Sb-p arm.The outcome of pCR had moderate-quality evidence and the outcome of pCR (with only RCTs) had high-quality evidence. CONCLUSIONS: Nab-paclitaxel exhibits short-term efficacy advantages over paclitaxel, but no significant long-term benefits. The two regimens have different safety profile.
Medical management of pancreatic cancer: from personalization to broadening treatment strategies.
Dusetti N, Bachet JB, Chanez B … +11 more , Neuzillet C, de Mestier L, Williet N, Frauhoffer N, Nicolle R, Boilève A, Turpin A, Rodriguez R, Cros J, Iovanna J, Hammel P
Cancer Treat Rev · 2025 Jul · PMID 40466554 · Publisher ↗
Pancreatic ductal adenocarcinoma (PDAC) is one of the most heterogeneous and deadly cancers. This review examines recently implemented strategies to integrate predictive tools and targeted therapies to improve treatments...
Pancreatic ductal adenocarcinoma (PDAC) is one of the most heterogeneous and deadly cancers. This review examines recently implemented strategies to integrate predictive tools and targeted therapies to improve treatments personalization and patient outcomes. Predictive transcriptomic signatures based on machine learning should optimize first-line chemotherapy selection, while organoid-based chemo-profiling could help late-line or non-standard treatments, particularly when transcriptomic signatures are unavailable to guide therapeutic decisions. Liquid biopsies enable real-time, non-invasive monitoring of tumour progression and resistance. Targeted therapies, even limited to a small subset of PDAC patients, exploit specific molecular vulnerabilities and several of those are under clinical evaluation to join PDAC armamentarium. Given PDAC's biological complexity, a multimodal approach combining predictive tools, functional testing, and molecularly-guided therapies is required to progress. Implementing those strategies in routine practice, combined with technological and clinical advances should enhance the precision, accessibility, and effectiveness of personalized PDAC treatment, as well as expand therapeutic options with new targets.
Adjuvant therapy after resection of intraductal papillary mucinous neoplasm-derived pancreatic cancer: A systematic review and meta-analysis.
Habib JR, Fatimi AS, Mahmud O … +10 more , Rompen IF, Kinny-Köster B, Daamen LA, He J, Quintus Molenaar I, Chiaro MD, Wolfgang CL, Javed AA, Besselink MG, PANC-PALS Consortium
Cancer Treat Rev · 2025 Jul · PMID 40450826 · Publisher ↗
INTRODUCTION: The management of intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic cancer is extrapolated from pancreatic intraepithelial neoplasm (PanIN)-derived pancreatic cancer. However, these cancers...
INTRODUCTION: The management of intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic cancer is extrapolated from pancreatic intraepithelial neoplasm (PanIN)-derived pancreatic cancer. However, these cancers are biologically and clinically distinct and evidence regarding the role of adjuvant therapy (AT) is unclear. The aim of this systematic review and meta-analysis was to consolidate current evidence regarding survival benefit of AT for IPMN-derived pancreatic cancer. METHODS: Systematic searches of the PubMed, Embase, Scopus, Web of Science, and Cochrane CENTRAL databases were performed from inception to February 2nd, 2025. Studies that reported survival analyses comparing AT versus surgery alone for resected IPMN-derived pancreatic cancer were included. Risk of bias was assessed using the Newcastle-Ottawa scale. Hazard ratios were pooled using generic inverse-variance random-effects models. RESULTS: A total of 26 studies were included in this review. All studies were observational and 16 had low risk of bias while 10 had high risk of bias. AT was not associated with an OS benefit on pooled multivariable analysis (HR: 0.78 [0.47, 1.28]) in the total population. In subgroups of patients with pathology node-positive (pN1 or pN2) disease, advanced T-stage and overall AJCC tumor stage, elevated CA19-9 (>37 IU), and poor grade of differentiation, AT was associated with OS benefit. CONCLUSIONS: Current data suggests that routine AT after resection of IPMN-derived pancreatic cancer is not associated with an OS benefit and may constitute overtreatment. However, patients with high-risk features such as large or high-grade tumors, nodal disease, and elevated CA19-9 may benefit from AT.
Key decision factors in second-line therapy: Expert insights on HR+/HER2-metastatic breast cancer post-CDK4/6 inhibitor progression.
Buonaiuto R, Botticelli A, Criscitiello C … +7 more , Dieci MV, Fusco N, Gerratana L, Lambertini M, Malapelle U, Malorni L, De Angelis C
Cancer Treat Rev · 2025 Jul · PMID 40450825 · Publisher ↗
The progression of HR+/HER2- metastatic breast cancer after treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) poses significant therapeutic challenges. Endocrine therapy (ET) remains a cornerstone of subseq...
The progression of HR+/HER2- metastatic breast cancer after treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) poses significant therapeutic challenges. Endocrine therapy (ET) remains a cornerstone of subsequent treatment, but its effectiveness depends on a nuanced understanding of clinical and genomic factors that drive therapy selection. For example, the duration of response to prior CDK4/6i therapy strongly predicts sensitivity to subsequent ET. Patients with prolonged responses to first-line therapy may benefit most from additional endocrine strategies, whereas those with rapid cancer progression often require alternative approaches. Clinical parameters such as disease burden, visceral involvement, and comorbidities also guide treatment decisions. Low-burden, indolent disease favors continued ET, whereas aggressive progression may necessitate the addition of targeted agents or a shift to chemotherapy. Genomic profiling via liquid or tissue biopsy should be integral to identifying actionable mutations and ensuring timely, individualized intervention. Molecular parameters, such as ESR1 mutations and PI3K pathway alterations, can predict therapeutic response, thus guiding treatment selection. This review underscores the importance of a personalized, evidence-based approach to the selection of endocrine-based therapy post-CDK4/6i failure, leveraging clinical insights and molecular diagnostics to optimize patient outcomes.
Paving the path ForwARd: Advances and challenges in androgen receptor targeting in breast cancer.
Sridhar N, Iwase T, Xie X … +3 more , Lee J, Damodaran S, Ueno NT
Cancer Treat Rev · 2025 Jul · PMID 40424861 · Publisher ↗
The role of androgen receptors (AR) in breast cancer is crucial for preclinical and clinical research. While AR-targeted therapy is a standard treatment for prostate cancer, the application of this therapeutic strategy t...
The role of androgen receptors (AR) in breast cancer is crucial for preclinical and clinical research. While AR-targeted therapy is a standard treatment for prostate cancer, the application of this therapeutic strategy to breast cancer has not been established. Indeed, AR is expressed in around 60-90% of breast cancers, making it imperative that we learn more about its prognostic and predictive impacts and targeting potential in breast cancer. Over the past decade, AR-targeted therapies ─ including AR antagonists and selective AR modulators ─ have shown promise in breast cancer treatment. However, an incomplete understanding of AR's role across breast cancer subtypes hinders clinical application. The lack of standardized AR expression thresholds further complicates patient selection, underscoring the urgent need for biomarker-driven strategies to optimize AR-targeted approaches in breast cancer. In this review, we provide an overview of a clinical perspective of AR in breast cancer by discussing AR biology, AR as a biomarker, and AR-targeted therapy development. We present our review with a particular emphasis on the distinct roles of AR in ER-positive (ER+) and ER-negative (ER-) breast cancer subtypes. Finally, the paper addresses the hurdles that have impeded the development of a robust clinical landscape for AR-targeted therapies and possible solutions for overcoming these challenges.
Induction chemotherapy followed by chemoradiotherapy for locally advanced cervical cancer: A systematic review and meta-analysis.
Andrade MO, Al-Alam OCM, Kim HJS … +9 more , Batista JPT, Dornellas DMS, Coelho RL, Borges VEL, Gouveia MC, Scaranti M, Bonadio RC, Gaillard S, Costa SCS
Cancer Treat Rev · 2025 Jul · PMID 40408847 · Publisher ↗
BACKGROUND: The addition of induction chemotherapy (ICT) prior to concomitant chemoradiotherapy (CCRT) in the treatment of locally advanced cervical cancer (LACC) is controversial, as trials have yielded conflicting resu...
BACKGROUND: The addition of induction chemotherapy (ICT) prior to concomitant chemoradiotherapy (CCRT) in the treatment of locally advanced cervical cancer (LACC) is controversial, as trials have yielded conflicting results. This study aims to evaluate the role of ICT followed by CCRT in LACC. METHODS: We systematically searched PubMed, Embase and Cochrane for studies with patients diagnosed with LACC receiving ICT followed by CCRT. Studies that included surgery, definitive radiotherapy (without concurrent chemotherapy), or immunotherapy were excluded. RESULTS: Among 5,282 screened studies, 20 met the inclusion criteria, representing 1,543 patients treated with ICT. A meta-analysis of the five controlled studies exhibited high heterogeneity in progression-free survival (PFS) and overall survival (OS), driven by the CIRCE trial - a study employing a platinum-gemcitabine ICT regimen lasting > 6 weeks. Sensitivity analysis excluding this trial demonstrated a significant improvement in PFS (HR 0.46; 95 % CI 0.31-0.69; p = 0.0002) and OS (HR 0.68; 95 % CI 0.47-0.99; p = 0.049) with the addition of ICT to CCRT, compared to CCRT alone. Meta-analysis of proportions revealed a 2-year OS of 84.1 % for studies utilizing platinum-paclitaxel compared to 72.2 % for platinum-gemcitabine (p-value for subgroup difference = 0.022). Studies with ICT duration of ≤ 6 weeks showed a 2-year OS of 84.8 % compared to 71.7 % for ICT duration > 6 weeks (p = 0.003). CONCLUSION: In patients with LACC, ICT + CCRT significantly improves PFS and OS compared to CCRT alone, provided that the ICT involves a platinum doublet with paclitaxel and is administered within ≤ 6 weeks.
Dealing with KRAS G12C inhibition in non-small cell lung cancer (NSCLC) - biology, clinical results and future directions.
Attili I, Corvaja C, Trillo Aliaga P … +4 more , Del Signore E, Spitaleri G, Passaro A, de Marinis F
Cancer Treat Rev · 2025 Jun · PMID 40381528 · Publisher ↗
KRAS G12C mutation occurs in ∼ 14 % of non-small cell lung cancer (NSCLC) patients and has been historically deemed undruggable, with immune-checkpoint inhibitors (ICIs) and platinum-based chemotherapy (PBC) representing...
KRAS G12C mutation occurs in ∼ 14 % of non-small cell lung cancer (NSCLC) patients and has been historically deemed undruggable, with immune-checkpoint inhibitors (ICIs) and platinum-based chemotherapy (PBC) representing the standard-of-care in the advanced setting. First-in-class, covalent KRAS G12C OFF-inhibitors sotorasib and adagrasib have revolutionized the therapeutic landscape and recently entered clinical practice. However, limited efficacy alongside toxicity profiles strengthen the need to design novel molecules and to optimize therapeutic strategies to address and overcome intrinsic and acquired resistance mechanisms. Moreover, KRAS G12C frequently co-occurs with STK11/KEAP1 mutations, that represent a negative prognostic factor, being associated with increased metastatic potential and reduced overall survival and poorer outcomes with ICIs. Furthermore, the high incidence of brain metastases is common in KRAS G12C-mutant NSCLC, and the efficacy of standard therapies and KRAS G12C inhibitors in treating or preventing central nervous system involvement is still suboptimal. In this context, novel inhibitors, such as broad-spectrum inhibitors targeting the active GTP-bound ON-state, pan-RAS ON inhibitors and allele-selective tricomplex inhibitors, have showed promising early clinical activity although their clinical utility needs to be further elucidated. In addition, targeting upstream, downstream and parallel signaling pathways through combination strategies might enhance the activity of KRAS G12C inhibitors and eventually improve clinical outcomes in this subset of NSCLC patients. Several combinations are currently under clinical investigation and promising approaches include combinations of KRAS G12C inhibitors with ICIs, SOS1, SHP2 inhibitors and PBC. Notwithstanding the potential improved efficacy of combination strategies, tolerability remains a critical challenge that must be carefully assessed and managed.
The present and the future of immunotherapy in hepatocellular carcinoma and biliary tract cancers.
Cabibbo G, Rimassa L, Lamarca A … +4 more , Masi G, Daniele B, Pinato DJ, Casadei-Gardini A
Cancer Treat Rev · 2025 Jun · PMID 40373702 · Publisher ↗
Hepatobiliary malignancies encompass a spectrum of invasive carcinomas arising in the liver [hepatocellular carcinoma (HCC), bile ducts [intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (EHC)] a...
Hepatobiliary malignancies encompass a spectrum of invasive carcinomas arising in the liver [hepatocellular carcinoma (HCC), bile ducts [intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (EHC)] and the gallbladder. These malignancies represent a growing global health burden, with rising incidence and mortality rates and their overall prognosis remains poor because many patients present with advanced unresectable disease at diagnosis. In recent years, significant advancements in understanding HCC immunogenicity have reshaped the therapeutic scenario of advanced HCC with the immunotherapy revolutionizing the current HCC treatment landscape and patients' prognosis. Moreover, the addition of immunotherapy to chemotherapy has recently established a new standard of care first-line treatment for patients with biliary tract cancers (BTCs) who had historically few therapeutic options. Currently, immunotherapy and immune checkpoint inhibitor (ICI)-based regimens stand as a valuable and practice-changing options in both HCC and BTC management. The mounting recent evidence supporting immunotherapy's survival benefit demands clinicians to stay updated with a rapidly evolving treatment landscape as well as gain knowledge about patient selection, response rate compared with other systemic treatments and immune-mediated adverse events (imAEs) management. A panel of international Experts, comprising hepatologists and oncologists, gathered to explore the challenges in effectively integrating immunotherapy in routine clinical practice. The aim of this review is to present the Experts' insights to inform treatment choice in HCC and BTC with a special emphasis on the role of currently available ICI-based therapies in shifting treatment paradigms and potentially reversing the natural course of these two deadly malignancies.
Drug-Drug interactions and special considerations in breast cancer patients treated with CDK4/6 inhibitors: A comprehensive review.
Sahin TK, Kavgaci G, Guven DC … +1 more , Aksoy S
Cancer Treat Rev · 2025 Jun · PMID 40367730 · Publisher ↗
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have reshaped the treatment paradigm of hormone receptor positive (HR + )/HER2-negative breast cancer in both adjuvant and metastatic settings. However, their metabolism v...
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have reshaped the treatment paradigm of hormone receptor positive (HR + )/HER2-negative breast cancer in both adjuvant and metastatic settings. However, their metabolism via the cytochrome P450 (CYP3A4) pathway poses a high risk of clinically relevant drug-drug interactions (DDIs), requiring vigilant therapeutic strategies. This review provides a comprehensive analysis of the pharmacokinetics, metabolism, and interaction profiles of palbociclib, ribociclib, and abemaciclib, emphasizing their differential DDI risks. Among these agents, ribociclib has been associated with a higher risk of QTc prolongation and CYP3A4-mediated interactions in some studies, whereas abemaciclib demonstrates a relatively favorable DDI profile. However, data remain limited and are largely derived from indirect comparisons or pharmacovigilance analyses. We further examine the clinical implications of drug-drug interactions with frequently co-prescribed agents, including proton pump inhibitors, antifungal medications, anticoagulants, and lipid-lowering therapies. Practical recommendations regarding drug selection, therapeutic drug monitoring, and dose adjustment are discussed with attention to the individual characteristics of each CDK4/6i. Dose modifications and monitoring in patients with renal or hepatic impairment are also discussed. Emerging pharmacogenomic data suggest that genetic polymorphisms in CYP3A4 and ABCG2 influence drug exposure and toxicity, reinforcing the need for personalized treatment approaches. As the use of CDK4/6i expands across different breast cancer settings, addressing DDIs through precision medicine strategies such as pharmacogenomic profiling, physiologically based pharmacokinetic modeling, and artificial intelligence-guided clinical support will be essential to personalize therapy and optimize safety.
Optimal bevacizumab treatment strategy in advanced ovarian cancer: A review.
Monk BJ, Lorusso D, Fujiwara K … +1 more , Sehouli J
Cancer Treat Rev · 2025 Jun · PMID 40349571 · Publisher ↗
Bevacizumab was the first targeted therapy developed for newly diagnosed and recurrent advanced ovarian cancer (AOC). Although bevacizumab has been approved for the treatment of AOC for several years, identifying patient...
Bevacizumab was the first targeted therapy developed for newly diagnosed and recurrent advanced ovarian cancer (AOC). Although bevacizumab has been approved for the treatment of AOC for several years, identifying patients who may benefit most from this treatment is still debated. Bevacizumab has been associated with improved progression-free survival (PFS) regardless of clinical risk, but in some countries the use of bevacizumab in the treatment of newly diagnosed AOC has been restricted to higher-risk patients (stage III inoperable or suboptimally debulked disease, or stage IV disease); this is primarily due to the findings of exploratory subgroup analyses from phase III trials that suggest only higher-risk patients derive an overall survival (OS) advantage with bevacizumab. Recently reported post hoc analyses from the PAOLA-1 trial of maintenance olaparib plus bevacizumab versus bevacizumab alone for patients with newly diagnosed AOC and homologous recombination deficiency-positive tumors suggested PFS and OS benefit was achieved in both lower-risk (with stage III disease who had undergone upfront surgery and had complete resection) and higher-risk (with stage III disease who had undergone upfront surgery and had residual disease or who had received neoadjuvant chemotherapy, or with stage IV disease) patients, prompting reassessment of the role of bevacizumab in lower-risk patients. This review examines the role of bevacizumab in the AOC treatment pathway by discussing its efficacy and safety in the first-line, maintenance and recurrent settings, and evaluates the clinical implications of bevacizumab use across risk groups and lines of therapy.
Chimeric antigen receptor NK cells for breast cancer immunotherapy.
Wu N, Yang N, Zhang S … +6 more , Wu H, Fang X, Lin W, Zhang Y, Qi X, Gong Y
Cancer Treat Rev · 2025 Jun · PMID 40305951 · Publisher ↗
Breast cancer, a predominant malignancy afflicting women globally, demands innovative therapeutic strategies beyond traditional treatments such as surgery, chemotherapy, radiotherapy, and endocrine therapy. Among the eme...
Breast cancer, a predominant malignancy afflicting women globally, demands innovative therapeutic strategies beyond traditional treatments such as surgery, chemotherapy, radiotherapy, and endocrine therapy. Among the emerging therapies, immunotherapy has demonstrated substantial promise, particularly employing chimeric antigen receptor (CAR) technology. This review elucidates the prospect of CAR-modified natural killer (NK) cells in treating breast cancer. NK cells, vital components of the immune system, possess the capability to non-specifically target and extinguish neoplastic cells. Through genetic engineering, CAR constructs targeting specific breast cancer antigens, including HER2, EGFR, PD-L1, MSLN, and Trop2, are integrated into NK cells, thereby enhancing their tumor recognition and cytotoxicity. The review delves into the structural optimization of CAR-NK cells, discussing design elements such as scFv, hinge regions, and activation signals, and emphasizes strategies to augment CAR-NK cell functionality and persistence within the tumor microenvironment. Combining CAR-NK cells with other therapeutic modalities (such as chemotherapy and checkpoint inhibitors) is explored to enhance therapeutic efficacy. Preclinical researches emphasized the efficacy of CAR-NK cells in targeting breast cancer cells, paving the way for future clinical applications and offering hope for improved outcomes in breast cancer patients.
Enhancing radiotherapy techniques for Triple-Negative breast cancer treatment.
Sarlak S, Pagès G, Luciano F
Cancer Treat Rev · 2025 May · PMID 40286498 · Publisher ↗
Breast cancer is the most prevalent cancer among women worldwide, with various subtypes that require distinct treatment approaches. Among these, Triple-Negative Breast Bancer (TNBC) is recognized as the most aggressive f...
Breast cancer is the most prevalent cancer among women worldwide, with various subtypes that require distinct treatment approaches. Among these, Triple-Negative Breast Bancer (TNBC) is recognized as the most aggressive form, often associated with poor prognosis due to its lack of targeted therapeutic options. This review specifically focuses on Radiotherapy (RT) as a treatment modality for TNBC, evaluating recent advancements and ongoing challenges, particularly the issue of radioresistance. RT remains an essential part in the management of breast cancer, including TNBC. Over the years, multiple improvements have been made to enhance RT effectiveness and minimize resistance. The introduction of advanced techniques such as Stereotactic Body Radiation Therapy (SBRT) and Stereotactic Radiosurgery (SRS) has significantly improved precision and reduced toxicity. More recently, proton radiation therapy, a novel RT modality, has been introduced, offering enhanced dose distribution and reducing damage to surrounding healthy tissues. Despite these technological advancements, a subset of TNBC patients continues to exhibit resistance to RT, leading to recurrence and poor treatment outcomes. To overcome radioresistance, there is an increasing interest in combining RT with targeted therapeutic agents that sensitize cancer cells to radiation. Radiosensitizing drugs have been explored to enhance the efficacy of RT by making cancer cells more susceptible to radiation-induced damage. Potential candidates include DNA damage repair inhibitors, immune checkpoint inhibitors, and small-molecule targeted therapies that interfere with key survival pathways in TNBC cells. In conclusion, while RT remains a crucial modality for TNBC treatment, radioresistance remains a significant challenge. Future research should focus on optimizing RT techniques while integrating radiosensitizing agents to improve treatment efficacy. By combining RT with targeted drug therapy, a more effective and personalized treatment approach can be developed, ultimately improving patient outcomes and reducing recurrence rates in TNBC.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe