Cancer treatment and research communications最新文献

{"title":"miR-150 in cancer metastasis: Orchestrating migration, invasion, and angiogenesis through context-dependent mechanisms","authors":"Belal Almajali ,&nbsp;Waleed K. Abdulsahib ,&nbsp;S.Renuka Jyothi ,&nbsp;Priya Priyadarshini Nayak ,&nbsp;Ashish Singh Chauhan ,&nbsp;Siya Singla ,&nbsp;Guzalya Mamedova ,&nbsp;Fadhil Faez Sead ,&nbsp;Pouria Salajegheh","doi":"10.1016/j.ctarc.2025.101048","DOIUrl":"10.1016/j.ctarc.2025.101048","url":null,"abstract":"<div><div>Metastasis, which accounts for approximately 90 % of cancer-related mortality, is driven by intricate regulatory networks that remain only partially understood. MicroRNA-150 (miR-150) has emerged as a pivotal, context-dependent regulator within these networks, displaying dual functionality as either a tumor suppressor or an oncogene, depending on tumor type, isoform (-5p/-3p), and microenvironmental cues. This comprehensive review synthesizes evidence highlighting miR-150′s regulation of critical metastatic processes—namely epithelial-mesenchymal transition, cell migration, invasion, extracellular matrix remodeling, and angiogenesis—through direct targeting of key molecular effectors and its dynamic integration into competitive endogenous RNA (ceRNA) networks involving long non-coding RNAs and circular RNAs. Notably, miR-150 primarily acts as a metastasis suppressor in solid tumors, such as breast, colorectal, and ovarian cancers, by inhibiting pro-metastatic signaling pathways. However, it paradoxically facilitates metastatic progression in specific contexts, including non-small cell lung cancer and cervical carcinoma, by activating oncogenic cascades through suppression of tumor suppressors. Clinically, reduced miR-150 expression serves as a robust indicator of advanced disease stage, lymph node involvement, and poor prognosis, while circulating exosomal miR-150 shows promise as a non-invasive diagnostic biomarker. Therapeutically, tailored strategies employing miR-150 mimics, antagomiRs, or ceRNA-targeted inhibitors hold potential for disrupting metastatic pathways; however, challenges such as isoform-specific targeting, precise delivery, and mitigation of off-target effects remain unresolved. In our view, framing miR-150 as a \"double-edged sword\" in metastatic regulation provides a conceptual framework for leveraging its molecular versatility to advance precision oncology and mitigate metastatic progression, particularly in combination with emerging systemic therapies.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"45 ","pages":"Article 101048"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of hypoxia on extracellular vesicles in malignant and non-malignant conditions","authors":"Vahid Niazi ,&nbsp;Soudeh Ghafouri-Fard","doi":"10.1016/j.ctarc.2025.100924","DOIUrl":"10.1016/j.ctarc.2025.100924","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) are produced by virtually all types of cells and can be detected in nearly all extracellular places. These particles mediate intercellular communication and transfer their cargo to the recipient cells, inducing a variety of processes in these cells through transmission of several biomolecules such as miRNAs, lncRNAs, other transcripts and a variety of proteins. It has been documented that size, quantity, and expression of biomolecules in the EVs are influenced by the level of oxygen. In fact, hypoxia can affect several cellular processes through modulation of the cargo of these vesicles. Hypoxic exosomes derived from tumor cells have several protumoral effects on the recipient cells, including enhancement of proliferation, migration, and invasion in other tumoral cells, induction of metastasis in distant organs, stimulation of angiogenesis in the endothelial cells, and modulation of macrophage polarization. Hypoxic EVs also contribute to several non-malignant diseases. This review summarizes the effect of hypoxia on EVs cargo in malignant and nonmalignant diseases of different organs.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"43 ","pages":"Article 100924"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"At-home autologous hematopoietic cell transplant for adults with hematological malignancies. How frailty impacts and evolves during HCT procedure. An observational, longitudinal, and prospective study","authors":"Juan Ortiz ,&nbsp;María Teresa Solano ,&nbsp;Cristina Gallego ,&nbsp;Nuria Ballestar ,&nbsp;Noemi de Llobet ,&nbsp;Laia Guardia ,&nbsp;Raquel Salinas ,&nbsp;Alexandra Martínez-Roca ,&nbsp;Beatriz Merchán ,&nbsp;Paola Charry ,&nbsp;Joan Cid ,&nbsp;Miquel Lozano ,&nbsp;Enric Carreras ,&nbsp;Sara Laxe ,&nbsp;Concepción Closa ,&nbsp;María Suárez-Lledó ,&nbsp;Laura Rosiñol ,&nbsp;Carmen Martínez ,&nbsp;Montserrat Rovira ,&nbsp;Francesc Fernández-Avilés ,&nbsp;María Queralt Salas","doi":"10.1016/j.ctarc.2025.100920","DOIUrl":"10.1016/j.ctarc.2025.100920","url":null,"abstract":"<div><h3>Introduction and aims</h3><div>Since April 2021, the frailty state of patients is evaluated routinely in adults undergoing auto-HCT at our institution using the HCT Frailty Scale. The scale categorises each candidate as either fit, pre-fit or frail.</div></div><div><h3>Methods</h3><div>Our study includes 80 consecutive adults with lymphoprolipherative disorders (LPD) and multiple myeloma (MM) undergoing at-home auto-HCT at our institution between June 2021 and June 2023. An initial evaluation of frailty was conducted at first consultation (pre-apheresis), followed by a subsequent evaluation at day +100.</div></div><div><h3>Results</h3><div>The median age was 58 years (range: 19–69), 41 (51.2 %) patients were males, 45 (56.3 %) were diagnosed with MM and 35 with LPD. At the initial consultation, 24 (30.0 %) adults were classified as fit, 48 (60.0 %) as pre-frail, and 8 (10.0 %) as frail. Frail patients were more likely to be older (OR 1.16 <em>P</em> = 0.077), and to have a KPS &lt; 90 % (OR 27, <em>P</em> = 0.012), and also exhibit a higher number of comorbidities (HCT-CI&gt;3: OR 11.9, <em>p</em> = 0.035). However, the underlying diagnosis did not impact the incidence of frailty at the initial consultation (OR 0.99, <em>p</em> = 0.999).</div></div><div><h3>Conclusions</h3><div>There was no association between the duration of at-home transplant hospitalisation and readmissions and the presence of frailty syndrome. Moreover, no patient died due to transplant-related toxicity. The results presented in this study support that at-home auto-HCT can be performed in fit, pre-frail, and frail adults with an experienced and multidisciplinary team. Although conclusions are limited by the reduced sample size, the observed differences on frailty incidences during patient's follow-up support that frailty is dynamic, and potentially amendable with specific interventions.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"43 ","pages":"Article 100920"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors influencing the diagnostic basis in pancreatic cancer. A study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort","authors":"Miquel Porta ,&nbsp;José Pumarega ,&nbsp;Àlex Giménez ,&nbsp;Anne Tjønneland ,&nbsp;María-Dolores Chirlaque ,&nbsp;Carlotta Sacerdote ,&nbsp;Magda Gasull ,&nbsp;Anja Olsen ,&nbsp;Marta Crous-Bou ,&nbsp;Sara Grioni ,&nbsp;Thérèse Truong ,&nbsp;Christina C. Dahm ,&nbsp;Sandra M. Colorado-Yohar ,&nbsp;Léa Bouteille ,&nbsp;Gianluca Severi ,&nbsp;Marie Breeur ,&nbsp;Calogero Saieva ,&nbsp;Marcela Guevara ,&nbsp;Salvatore Panico ,&nbsp;Rosario Tumino ,&nbsp;Verena Katzke","doi":"10.1016/j.ctarc.2025.101009","DOIUrl":"10.1016/j.ctarc.2025.101009","url":null,"abstract":"<div><h3>Background and aims</h3><div>Substantial differences have been reported in risk estimates for etiologic factors of pancreatic cancer among subjects with different degrees of diagnostic certainty. The aim of the study was to assess the influence of some personal and social characteristics on the diagnostic basis in individuals with pancreatic cancer.</div></div><div><h3>Methods</h3><div>We analyzed 393 participants from the EPIC cohort with a diagnosis of pancreatic cancer and information on the basis of diagnosis. Two main groups of cases were compared: one in which microscopic confirmation (MC) was available to diagnose pancreatic cancer (including autopsy, histology, cytology or hematology), and one in which non-microscopic methods were used (biochemical, immunological or image tests, exploratory surgery, clinical observation, self-report, or death certificate).</div></div><div><h3>Results</h3><div>The diagnosis of pancreatic cancer of 73% of participants was achieved through MC. While, overall, over 82% of men had MC, this figure was 65% in women (p&lt;0.001). Subjects with MC, both men and women, were younger at diagnosis than participants diagnosed by non-microscopic methods. Younger women (&lt;60 years) had a higher probability of having their cancer diagnosed with MC (OR=2.54, 95% CI 1.04-6.17) than women ≥70 years. After the year 2000 the chances of having the disease diagnosed through MC increased more than 2-fold in women and more than 5-fold in men. No significant differences in diagnostic basis were observed by educational level, comorbidities or established risk factors for pancreatic cancer.</div></div><div><h3>Conclusion</h3><div>The rates of MC in subjects diagnosed with pancreatic cancer continued to be relatively low. Age and sex are the two main factors that powerfully influence MC. Hence, age and sex must be considered when designing and analyzing clinical and epidemiological studies, as well as in clinical practice. The consistently lower rates of MC in female patients suggest an ingrained sex-related diagnostic bias, which may require specific policies to be counterbalanced.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"45 ","pages":"Article 101009"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic value of FBXW7 tumor suppressor gene expression and mutations in patients with colorectal cancer: A meta-analysis","authors":"Mohammad Rahmanian ,&nbsp;Iman Elahi Vahed ,&nbsp;Mohammad Shirali ,&nbsp;Raheleh Charmchi ,&nbsp;Amirreza Noura ,&nbsp;Narges Khaleghi gazik ,&nbsp;Reza Senobari ,&nbsp;Zahra Rasouli ,&nbsp;Mohammadsadegh Jafari ,&nbsp;Shokoofeh Noori","doi":"10.1016/j.ctarc.2025.100988","DOIUrl":"10.1016/j.ctarc.2025.100988","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer (CRC) ranks as the second most common cause of cancer-related mortality globally. The tumor suppressor gene FBXW7 is considered to play a key role in determining patient prognosis. This study aims to assess the impact of FBXW7 gene mutations on the prognosis of CRC patients.</div></div><div><h3>Methods</h3><div>A thorough search of different databases, including PubMed, Scopus, Web of Science, and Google Scholar, was performed. Hazard ratios (HRs) along with 95 % confidence intervals (CIs) were utilized to assess the effect of reduced expression or mutation of FBXW7 on disease-free survival (DFS) of CRC patients or their overall survival (OS).</div></div><div><h3>Results</h3><div>This meta-analysis, which included 15 studies, found that low FBXW7 expression or mutations were strongly linked to poorer OS (HR=1.60, 95 % CI= 1.25 to 2.04, I²=65 %) and DFS (HR=2.14, 95 % CI= 1.33 to 3.43, I²=61 %). Sensitivity analyses did not identify any study as a significant source of heterogeneity, and no evidence of publication bias was observed. Studies with ≥36 months of follow-up demonstrated significant OS association (HR=1.62, 95 % CI= 1.20 to 2.17), unlike those with shorter follow-up periods. Both mutation-based studies (HR=1.38, 95 % CI= 1.08 to 1.77) and expression-based studies (HR=2.45, 95 % CI= 1.70 to 3.54) indicated poorer OS, while DFS correlation was significant only in expression-based studies (HR=2.41, 95 % CI= 1.43 to 4.07). The strongest relationship with OS was observed in studies from China (HR=1.99, 95 % CI= 1.27 to 3.12) and the USA (HR=1.63, 95 % CI= 1.17 to 2.26), while the correlation with DFS was mainly seen in non-Chinese studies (HR=3.03, 95 % CI= 1.22 to 7.53).</div></div><div><h3>Conclusion</h3><div>This study suggests that FBXW7 reduced expression or mutations are linked to worse OS and DFS in CRC patients.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"45 ","pages":"Article 100988"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145027012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The cognitive survivorship model: Bridging neuro-oncology and neurology","authors":"Sahar Hemeda ,&nbsp;Mohammed Elmadani ,&nbsp;József Janszky ,&nbsp;Dávid Pintér ,&nbsp;Mate Orsolya ,&nbsp;Norbert Kovács","doi":"10.1016/j.ctarc.2025.100998","DOIUrl":"10.1016/j.ctarc.2025.100998","url":null,"abstract":"<div><div>Cognitive impairment is a prevalent yet often overlooked consequence of cancer and neurodegenerative diseases, substantially impacting the quality of life, daily functioning, and emotional well-being of affected individuals. Despite differing pathologies, both groups exhibit similar cognitive and psychological symptoms, including memory loss, attention deficits, depression, anxiety, and caregiver strain, which frequently persist long after the initial treatment. These symptoms are attributed to shared biological mechanisms, such as neuroinflammation, oxidative stress, and white matter disruption. However, cognitive health has seldom been systematically addressed in cancer or neurology survivorship care, resulting in gaps in long-term support for patients. Recent advances in neuroscience and rehabilitation science, including evidence for non-pharmacological interventions such as cognitive training, mindfulness, and physical activity, underscore the potential for a unified interdisciplinary model. Digital health technologies and telehealth tools have enhanced access and scalability, particularly in remote and underserved populations. In this Opinion article, we propose a Cognitive Survivorship Model (CSM) that integrates oncology and neurology to reframe survivorship from a cognitive health perspective. The model encompasses pillars such as routine cognitive screening, cognitive rehabilitation, psychological support, lifestyle interventions, and caregiver training, supported by digital delivery and policy advocacy. By bridging neuro-oncology and neurology, this model offers a roadmap for person-centred, scalable, and interdisciplinary post-treatment care. We advocate for clinical adoption, policy reform, and further research to validate and implement this model across diverse healthcare systems. Cognitive survivorship must be recognised not as a specialty niche but as a critical component of comprehensive post-diagnosis care.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"45 ","pages":"Article 100998"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the relevant factors of lymph node metastasis in No.253 lymph node of rectal cancer patients","authors":"Yu-Xi Gao ,&nbsp;Shi-Xiang Pan ,&nbsp;Fang Hu ,&nbsp;Bo Li ,&nbsp;Shou-Guang Wang","doi":"10.1016/j.ctarc.2025.100989","DOIUrl":"10.1016/j.ctarc.2025.100989","url":null,"abstract":"<div><h3>Objective</h3><div>Lymph node metastasis is the primary metastasis of colorectal cancer, and it is of positive significance to explore the characteristics and potential influencing factors of lymph node metastasis in colorectal cancer patients to guide the treatment and improve the prognosis of patients.</div></div><div><h3>Method</h3><div>The clinical data of 760 patients with rectal cancer (D3) who underwent radical rectal cancer (D3) resection in the Affiliated Hospital of Qingdao University from October 2017 to October 2022 were retrospectively analysed.</div></div><div><h3>Result</h3><div>Among the 760 patients, 314 was lymph node-positive, of which 26 was positive for the No.253 lymph node. Univariate analysis showed that CEA level, tumor T stage, tumor N stage, number of lymph nodes metastasised, and vascular tumor thrombus were risk factors for lymph node metastasis in No.253 lymph node of rectal cancer. Multivariate analysis showed that CEA level (CEA&gt;5 ng/ml), number of lymph nodes metastasised, and vascular cancer thrombus were independent risk factors for lymph node metastasis in No.253 lymph node of rectal cancer patients.</div></div><div><h3>Conclusion</h3><div>The risk of lymph node metastasis in No.253 lymph node was higher in rectal cancer patients with high CEA levels, late tumor TNM stage, number of lymph node metastases, and positive vascular thrombus. CEA level (CEA&gt;5 ng/ml), number of lymph nodes metastasised, and vascular cancer thrombus were independent risk factors for lymph node metastasis in No.253 lymph node of rectal cancer patients.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"45 ","pages":"Article 100989"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the tozzi classification system in diaphragm surgeries for advanced ovarian cancer: Clinical applicability and perioperative outcomes","authors":"Divya Panyam Vuppu ,&nbsp;Priya Bhati ,&nbsp;Saumya Gupta ,&nbsp;Sheejamol V S ,&nbsp;Nitu Puthenveettil","doi":"10.1016/j.ctarc.2025.100958","DOIUrl":"10.1016/j.ctarc.2025.100958","url":null,"abstract":"<div><h3>Background</h3><div>Over 70 % of advanced ovarian cancer cases involve metastasis to the peritoneum, diaphragm, and liver. Standardised diaphragm surgeries are vital for achieving complete cytoreduction and enhancing patient prognosis.</div></div><div><h3>Aim</h3><div>This study evaluates the clinical utility of Tozzi’s classification for diaphragm surgeries and examines perioperative outcomes in advanced ovarian cancer debulking.</div></div><div><h3>Methods</h3><div>Patients who underwent diaphragm surgery during cytoreductive procedures for ovarian cancer were classified using Tozzi’s classification based on disease extent, and liver mobilisation and perioperative outcomes were analysed.</div></div><div><h3>Results</h3><div>Among 38 patients (71 % stage III; 52.6 % interval surgeries), 39.4 % were Type I, 28.9 % Type II, and 31.5 % Type III. Ascites was more common in Type II (77.8 %, <em>p</em> = 0.04), while Type III had more imaging-detected lesions (83.3 %, <em>p</em> = 0.03). Type III surgeries required longer durations (405 ± 136 min, <em>p</em> = 0.04) and more intraoperative interventions (58.3 %, <em>p</em> = 0.01). ICU care was needed in 50 % of cases, with a median stay of two days, mainly for Type III. Pulmonary complications occurred in 10.5 %, and the median hospital stay was six days.</div></div><div><h3>Conclusion</h3><div>Tozzi’s classification predicts surgical complexity and morbidity, particularly for Type III cases, aiding surgical planning and optimising patient outcomes.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"44 ","pages":"Article 100958"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144587712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing PUMA's lethal potential: BCL-2 family dynamics and novel strategies to combat cancer recurrence.","authors":"Moustafa A Mansour, Mohamed Abdel-Fattah El-Salamoni, Hamdi Nabawi Mostafa","doi":"10.1016/j.ctarc.2025.100975","DOIUrl":"10.1016/j.ctarc.2025.100975","url":null,"abstract":"<p><p>Cancer cells often survive treatment by blocking the natural process of cell death, allowing them to return and grow again. The BCL-2 protein family plays a central role in this process, controlling whether a cell lives or dies. Among its members, the BH3-only proteins initiate the apoptotic cascade in response to cellular stress. PUMA (p53-upregulated modulator of apoptosis), a pro-apoptotic BH3-only protein, is the most potent of its subclass, binding all major anti-apoptotic BCL-2 family members (Bcl-xL, Bcl-2, Mcl-1, and Bcl-w) to counteract their inhibition of Bax and Bak. Upon activation, Bax/Bak form pores in the mitochondrial membrane, releasing apoptogenic factors such as cytochrome c, SMAC, and apoptosis-inducing factor, ultimately triggering caspase-mediated cell death. Due to its upstream role in apoptosis, PUMA deficiency or inhibition by anti-apoptotic proteins promotes cancer development and therapy resistance. Conversely, elevated PUMA expression sensitizes cancer cells to chemo- and radiotherapy. Accumulating evidence positions PUMA as a universal sensor of cell death stimuli and a promising therapeutic target in cancer. This article critically examines PUMA's regulation, function, and potential as a target for cancer treatment.</p>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"44 ","pages":"100975"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic therapy breakthroughs in the management of brain metastases: A new era for HER2-positive breast cancer","authors":"Martina Parenza Arenhardt ,&nbsp;Carolina Martins Vieira ,&nbsp;Angélica Nogueira-Rodrigues","doi":"10.1016/j.ctarc.2025.100997","DOIUrl":"10.1016/j.ctarc.2025.100997","url":null,"abstract":"<div><div>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.</div><div>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.</div><div>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 (IC<img>ORR) of 45.5 % in untreated and 45.2 % in treated BMs. Smaller studies, such as DEBBRA and TUXEDO-1, demonstrated IC<img>ORRs 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 IC<img>ORR of 62.3 %, with the highest responses (82.6 %) in untreated BMs.</div><div>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.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"45 ","pages":"Article 100997"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}