RARRES2's impact on lipid metabolism in triplenegative breast cancer:a pathway to brain metastasis

Breast cancer brain metastasis(BCBrM)is a crucial and hard area of research which guarantees an urgent need to understand the underlying molecular mechanisms.A recent study by Li et al.[1]published in Military Medical Research investigated the role of retinoic acid receptor responder 2(RARRES2)in regulating lipid metabolism in BCBrM,highlighting the clinical relevance of alterations in lipid metabolites,such as phosphatidylcholine(PC)and triacylglycerols(TAGs),by RARRES2 through the modulation of phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway.This commentary aims to elaborate on the key findings and their relevance to the field.

RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

Inetetamab combined with pyrotinib and chemotherapy in the treatment of breast cancer brain metastasis: A case report

BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In this context,we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb(ine-tetamab)combined with a small molecule tyrosine kinase inhibitor(TKI).CASE SUMMARY The patient was a 58-year-old woman with a 12-year history of type 2 diabetes.She was compliant with regular insulin treatment and had good blood glucose control.The patient was diagnosed with invasive carcinoma of the right breast(T3N1M0 stage IIIa,HER2-positive type)through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019.Immunohistochemistry showed ER(-),PR(-),HER-2(3+),and Ki-67(55-60%+).Preoperative neoadjuvant chemotherapy,i.e.,the AC-TH regimen(epirubicin,cyclophosphamide,docetaxel-paclitaxel,and trastuzumab),was administered for 8 cycles.She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year.Brain metastasis was found 9 mo after surgery.She underwent brain metastasectomy in August 2020.Immunohistochemistry showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache symptoms.After an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and capecitabine.Whole-brain radiotherapy was recommended.The patient and her family refused radiotherapy for personal reasons.In September 2021,a routine examination revealed that the brain tumor was considerably larger.The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine examinations.The patient’s condition is generally stable,and she has a relatively high quality of life.This case report demonstrates that in patients with BCBM and resistance to trastuzumab,inetetamab combined with pyrotinib and chemotherapy can prolong survival.CONCLUSION Inetetamab combined with small molecule TKI drugs,chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.

Prognostic factors of breast cancer brain metastasis

In this editorial we comment on the article by Chen et al published in the recent issue of the World Journal of Clinical Oncology.Brain metastasis is one of the most serious complications of breast cancer and causes high morbidity and mortality.Brain metastases may involve the brain parenchyma and/or leptomeninges.Symptomatic brain metastases develop in 10%-16%of newly recognized cases each year,and this rate increases to 30%in autopsy series.Depending on the size of the metastatic foci,it may be accompanied by extensive vasogenic edema or may occur as small tumor foci.Since brain metastases are a significant cause of morbidity and mortality,early diagnosis can have significant effects on survival and quality of life.The risk of developing brain metastases emerges progressively due to various patient and tumor characteristics.Patient variability may be particularly important in the susceptibility and distribution of brain metastases because malignant blood must cross the brain barrier and move within the brain parenchyma.Some characteristics of the tumor,such as gene expression,may increase the risk of brain metastasis.Clinical growth,tumor stage,tumor grade,growth receptor positivity,HER2 positivity,molecular subtype(such as triple negative status,luminal/nonluminal feature)increase the risk of developing breast cancer metastasis.Factors related to survival due to breast cancer brain metastasis include both tumor/patient characteristics and treatment characteristics,such as patient age,lung metastasis,surgery for brain metastasis,and HER2 positivity.If cases with a high risk of developing brain metastasis can be identified with the help of clinical procedures and artificial intelligence,survival and quality of life can be increased with early diagnosis and treatment.At the same time,it is important to predict the formation of this group in order to develop new treatment methods in cases with low survival expectancy with brain metastases.

Navigating breast cancer brain metastasis:Risk factors,prognostic indicators,and treatment perspectives

In this editorial,we comment on the article by Chen et al.We specifically focus on the risk factors,prognostic factors,and management of brain metastasis(BM)in breast cancer(BC).BC is the second most common cancer to have BM after lung cancer.Independent risk factors for BM in BC are:HER-2 positive BC,triplenegative BC,and germline BRCA mutation.Other factors associated with BM are lung metastasis,age less than 40 years,and African and American ancestry.Even though risk factors associated with BM in BC are elucidated,there is a lack of data on predictive models for BM in BC.Few studies have been made to formulate predictive models or nomograms to address this issue,where age,grade of tumor,HER-2 receptor status,and number of metastatic sites(1 vs>1)were predictive of BM in metastatic BC.However,none have been used in clinical practice.National Comprehensive Cancer Network recommends screening of BM in advanced BC only when the patient is symptomatic or suspicious of central nervous system symptoms;routine screening for BM in BC is not recommended in the guidelines.BM decreases the quality of life and will have a significant psychological impact.Further studies are required for designing validated nomograms or predictive models for BM in BC;these models can be used in the future to develop treatment approaches to prevent BM,which improves the quality of life and overall survival.

Research Progress in Brain Metastasis of Breast Cancer

The incidence rate of breast cancer is very high.Some patients were diagnosed as stage IV patients at the first diagnosis and had distant metastasis.Bone,lung and liver are the common metastatic sites of breast cancer.Although brain is the least common metastatic site of breast cancer,the incidence of brain metastasis in newly diagnosed breast cancer patients is increasing year by year.After brain metastasis,the disease develops rapidly,and because of the existence of blood cerebrospinal fluid barrier,it is difficult for drugs to reach the focus,and the curative effect is poor,leading to poor prognosis of patients with brain metastasis of breast cancer.Previous studies have also explored the clinical characteristics of brain metastases from breast cancer and the factors affecting prognosis.Different ages,races,histological grades,T stages,N stages,molecular subtypes,and pathological types are the main factors affecting the occurrence and prognosis of brain metastases from breast cancer.Studies on the characteristics,mechanisms,and treatment plans of brain metastases from breast cancer have also been reported at home and abroad.This article reviews the clinical characteristics,pathogenesis and treatment progress of brain metastases from breast cancer,aiming to provide some ideas and basis for clinical diagnosis and treatment and drug research of brain metastases from breast cancer.

Analysis of clinicopathological features and prognostic factors of breast cancer brain metastasis

BACKGROUND Breast cancer(BC)has become the most common malignancy in women.The incidence and detection rates of BC brain metastasis(BCBM)have increased with the progress of imaging,multidisciplinary treatment techniques and the extension of survival time of BC patients.BM seriously affects the quality of life and survival prognosis of BC patients.Therefore,clinical research on the clinicopathological features and prognostic factors of BCBM is valuable.By analyzing the clinicopathological parameters of BCBM patients,and assessing the risk factors and prognostic indicators,we can perform hierarchical diagnosis and treatment on the high-risk population of BCBM,and achieve clinical benefits of early diagnosis and treatment.AIM To explore the clinicopathological features and prognostic factors of BCBM,and provide references for diagnosis,treatment and management of BCBM.METHODS The clinicopathological data of 68 BCBM patients admitted to the Air Force Medical Center,Chinese People’s Liberation Army(formerly Air Force General Hospital)from 2000 to 2022 were collected.Another 136 BC patients without BM were matched at a ratio of 1:2 based on the age and site of onset for retrospective analysis.Categorical data were subjected to χ^(2) test or Fisher’s exact probability test,and the variables with P<0.05 in the univariate Cox proportional hazards model were incorporated into the multivariate model to identify high-risk factors and independent prognostic factors of BCBM,with a hazard ratio(HR)>1 suggesting poor prognostic factors.The survival time of patients was estimated by the Kaplan-Meier method,and overall survival was compared between groups by log-rank test.RESULTS Multivariate Cox regression analysis showed that patients with stage Ⅲ/Ⅳ tumor at initial diagnosis[HR:5.58,95% confidence interval(CI):1.99–15.68],lung metastasis(HR:24.18,95%CI:6.40-91.43),human epidermal growth factor receptor 2(HER2)-overexpressing BC and triple-negative BC were more prone to BM.As can be seen from the prognostic data,52 of the 68 BCBM patients had died by the end of follow-up,and the median time from diagnosis of BC to the occurrence of BM and from the occurrence of BM to death or last follow-up was 33.5 and 14 mo,respectively.It was confirmed by multivariate Cox regression analysis that patients with neurological symptoms(HR:1.923,95%CI:1.005-3.680),with bone metastasis(HR:2.011,95%CI:1.056-3.831),and BM of HER2-overexpressing and triple-negative BC had shorter survival time.CONCLUSION HER2-overexpressing,triple-negative BC,late tumor stage and lung metastasis are risk factors of BM.The presence of neurological symptoms,bone metastasis,and molecular type are influencing prognosis factors of BCBM.

Prognostic factors affecting long-term outcomes in patients with brain metastasis from esophageal carcinoma

Objective: The incidence of brain metastasis from esophageal cancer(BMEC) has increased in recent years.Thus, it is necessary to identify factors that affect long-term outcomes for such patients.Methods: From January 1997 to July 2018, consecutive patients(10,043 patients, 31 with brain metastasis) with esophageal cancer(EC) treated at Zhejiang Cancer Hospital were recruited for retrospective analysis.Demographic, clinical, and pathological variables and the survival data were retrieved.Results: The median time from diagnosis of EC to diagnosis of brain metastases was 7.67(range, 0.43-55.20)months. The median survival time of BMEC patients from diagnosis of primary esophageal tumor was 16.7(range,2.33-163.30) months and the median survival time from the point of diagnosis of brain metastasis was 6.47(range,0.43-148.13) months. Univariate and multivariate analyses showed that the pathology type, EC without chemotherapy, and bone metastasis history were significantly associated with a shorter time interval between the first treatment of EC and brain metastasis. Chemotherapy history after brain metastasis, whole brain radiation therapy(WBRT) history, and surgery were significant predictors for better long-term survival outcomes.Conclusions: Our findings indicate that the use of surgery, WBRT, and chemotherapy can achieve the best therapeutic effects for BMEC patients.

Brain metastasis in non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations： a report of seven cases and literature review

Brain metastasis(BM)arising from non-small cell lung cancer(NSCLC)with rare epidermal growth factor receptor(EGFR)mutations is quite rare.The prognosis and therapeutic effects of BM remain enigmatic.To the best of our knowledge,this is the first report to make a separate analysis of BM from NSCLC patients with original uncommon EGFR mutations.We retrospectively reviewed 7 cases of BM arising from 42 cases of uncommon EGFR mutated lung cancer in Tianjin Medical University Cancer Institute and Hospital.We also performed a literature review to assess therapeutic features and outcomes.

Recursive Partitioning Analysis Classification and Graded Prognostic Assessment for Non-Small Cell Lung Cancer Patients with Brain Metastasis:A Retrospective Cohort Study

Objective：To assess prognostic factors and validate the effectiveness of recursive partitioning analysis （RPA） classes and graded prognostic assessment （GPA） in 290 non-small cell lung cancer （NSCLC） patients with brain metastasis （BM）.Methods：From Jan 2008 to Dec 2009,the clinical data of 290 NSCLC cases with BM treated with multiple modalities including brain irradiation,systemic chemotherapy and tyrosine kinase inhibitors （TKIs） in two institutes were analyzed.Survival was estimated by Kaplan-Meier method.The differences of survival rates in subgroups were assayed using log-rank test.Multivariate Cox＇s regression method was used to analyze the impact of prognostic factors on survival.Two prognostic indexes models （RPA and GPA） were validated respectively.Results：All patients were followed up for 1-44 months,the median survival time after brain irradiation and its corresponding 95% confidence interval （95% CI） was 14 （12.3-15.8） months.1-,2-and 3-year survival rates in the whole group were 56.0%,28.3%,and 12.0%,respectively.The survival curves of subgroups,stratified by both RPA and GPA,were significantly different （P0.001）.In the multivariate analysis as RPA and GPA entered Cox＇s regression model,Karnofsky performance status （KPS） ≥ 70,adenocarcinoma subtype,longer administration of TKIs remained their prognostic significance,RPA classes and GPA also appeared in the prognostic model.Conclusion：KPS ≥70,adenocarcinoma subtype,longer treatment of molecular targeted drug,and RPA classes and GPA are the independent prognostic factors affecting the survival rates of NSCLC patients with BM.

Brain metastasis in advanced colorectal cancer： results from the South Australian metastatic colorectal cancer (SAmCRC) registry

Objective:Brain metastasis is considered rare in metastatic colorectal cancer(mCRC);thus,surveillance imaging does not routinely include the brain.The reported incidence of brain metastases ranges from 0.6% to 3.2%.Methods:The South Australian mCRC Registry(SAmCRC)was analyzed to assess the number of patients presenting with brain metastasis during their lifetime.Due to small numbers,a descriptive analysis is presented.Results:Only 59 patients of 4,100 on the registry at the time of analysis had developed brain metastasis(1.4%).The clinical characteristics of those with brain metastasis were as follows:the median age was 65.3 years and 51% were female.Where the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog(KRAS)mutation status of the tumor was known,the majority harbored a KRAS mutation(55%);31(53%)underwent craniotomy and 55(93%)underwent whole-brain radiotherapy.The median survival time from diagnosis of brain metastasis was 4.2 months(95% confidence interval 2.9–5.5).Patients who underwent craniotomy and radiotherapy had superior survival compared to those who underwent whole-brain radiotherapy(8.5 months vs.2.2 months,respectively).Data from the SAmCRC(a population-based registry)confirm that brain metastases are rare and the median time to development is approximately 2 years.Conclusions:Brain metastasis is a rare outcome in advanced CRC.Patients within the registry tended to be female,young in age,and harbored with higher rates of KRAS mutations.Whether routine surveillance brain scanning should be considered remains controversial given the relative rarity of developing brain metastases in mCRC and ultimately,most patients with central nervous system involvement die from their extracranial disease.

Implications of the autophagy core gene variations on brain metastasis risk in non-small cell lung cancer treated with EGFR-TKI

Objective The brain is the main site of failure in cancer patients with epidermal growth factor receptor(EGFR)mutations undergoing treatment.However,identifying patients who may develop brain metastases(BM)is difficult.Autophagy is critical for cancer initiation and progression.We hypothesized that genetic variants in autophagy core genes might contribute to BM risk of non-small cell lung cancer(NSCLC)following treatment with EGFR tyrosine kinase inhibitor(EGFR-TKIs).Methods We systematically examined 16 potentially functional genetic polymorphisms in seven autophagy core genes among 105 TKI-treated NSCLC patients.Kaplan-Meier curves were plotted to assess the cumulative BM probability.Univariate and multivariate Cox proportional hazard regression analyses were utilized to calculate hazard ratios(HRs)and 95%confidence intervals(CIs).We evaluated the potential associations of these genes with subsequent BM development.Results We found that ATG16L1:rs2241880,ATG10:rs10036653,rs3734114,and ATG3:rs7652377 are significantly associated with NSCLC treated with EGFR-TKIs(all P<0.05).BM developed more often in patients with ATG3 rs7652377 CC genotype(33%),ATG10 rs10036653 AA genotype(43%),ATG10:rs3734114 CT/CC genotype(46%),and ATG16L1 rs2241880 AA genotype(37%)compared to patients with AA genotypes at rs7652377(12%),AT/TT genotypes at rs10036653(16%),the TT genotype at rs3734114(13%),or AG/GG genotypes at rs2241880(17%).Conclusion These associations may be critical for understanding the role of autophagy in BM risk.Future prospective studies are needed to determine if prophylactic cranial irradiation(PCI)could offer a survival benefit in this group of patients.

Prognostic scoring system for synchronous brain metastasis at diagnosis of colorectal cancer: A population-based study

BACKGROUND Brain metastasis(BM)from colorectal cancer(CRC)is rarely encountered clinically,and its prognosis has not been fully evaluated.AIM To construct a scoring system and accurately predict the survival of patients with synchronous BM at diagnosis of CRC.METHODS A retrospective study of 371 patients with synchronous BM from CRC was performed,using the data from 2010 to 2014 from the Surveillance,Epidemiology,and End Results database.Survival time and prognostic factors were statistically analyzed by the Kaplan-Meier method and Cox proportional hazards models,respectively.A scoring system was developed using the independent prognostic factors,and was used to measure the survival difference among different patients.RESULTS For the 371 patients,the median overall survival was 5 mo,survival rates were 27%at 1 year and 11.2%at 2 years.Prognostic analysis showed that age,carcinoembryonic antigen level and extracranial metastasis to the liver,lung or bone were independent prognostic factors.A scoring system based on these three prognostic factors classified the patients into three prognostic subgroups(scores of 0-1,2-3,and 4).The median survival of patients with scores of 0-1,2-3 and 4 was 14,5 and 2 mo,respectively(P<0.001).Subgroup analysis showed that there were significant differences in prognosis among the groups.Score 2-3 vs 0-1:hazard ratio(HR)=2.050,95%CI:1.363-3.083;P=0.001;score 4 vs 0-1:HR=3.721,95%CI:2.225-6.225;P<0.001;score 2-3 vs 4:HR=0.551,95%CI:0.374-0.812;P=0.003.CONCLUSION The scoring system effectively distinguishes long-term and short-term survivors with synchronous BM from CRC.These results are helpful in providing a reference for guiding therapy.

Surgery Versus Stereotactic Radiosurgery for Single Synchronous Brain Metastasis from Non-Small Cell Lung Cancer

Objective： The aim of this study is to compare the effectiveness of surgery with stereotactic radiosurgery （SRS） for patients with a single synchronous brain metastasis from successfully treated non-small cell lung cancer. Methods： Between 1995 and 2002, 53 patients underwent resection of both primary non-small cell lung cancer and the associated single brain metastasis. There were 33 men and 20 women with a mean age of 57 years （range, 32-85 years）. At the time of diagnosis, 42 patients experienced lung cancer related symptoms, whereas 11 patients experienced brain metastases-related symptoms. 42 patients had received thoracic surgery first, and 11 patients had undergone neurosurgery or radiosurgery first. Pneumonectomy was performed in 9 out of 42 patients （21.4%）, lobectomies in 30 （71.4%）, and wedge resection in 3 （7.2%）. 48 patients （90.5%） underwent complete lymphadenectomy. 35 patients underwent brain metastasectomy. 18 underwent SRS. Results： There was no postoperative mortality and severe complications after either lung or brain surgery. Histology showed 34 adenocarcinomas, 16 squamous cell carcinomas, and 3 large cell lung cancers. 15 patients （28.3%） had no evidence of lymph node metastases （No）, 20 patients （37.7%） had hilar metastases （N1）, and 18 patients （34%） had mediastinal metastases （N2）. The 1-, 2-, 3- and 5-year overall survival rates were 49%, 19%, 10%, and 5%, respectively. The corresponding data for neurosurgery group were 55%, 17%, 11%, and 6%, respectively. The median survival time was 13 months. For SRS group the corresponding data were 44.8%, 20.9% 10.5%, and 2%, respectively. The median survival time was 14 months. The differences between the two groups were not significant （P〉0.05）. In lymph node negative patients （No）, the overall 5-year survival rate was 10%, as compared with a 1% survival rate in patients with lymph node metastases （N1-2）. The difference was significant （P〈0,01）. For adenocarcinomas, the 5-year survival rate was 5%. The correspondent data for squamous cell lung cancers was 3%. The difference was not significant （P〉0.05）. Conclusion： Although the overall survival rate for patients who have brain metastases from NSCLC is poor, surgical resection or radiosurgery may be beneficial in a select group of patients with synchronous brain metastases and lung cancer without lymph node metastases.

Brain Metastasis of Uterine Leiomyosarcoma: A Case Report and Review of the Literature

The metastases of uterine leiomyosarcoma to the brain are exceptional and such cases are seldomly reported in the literature. The diagnosis is based on CT and brains MRI findings, in association with a gynecological history of cancer. Their management still stays without guidelines, and the surgical total resection is known to be the only way to influence positively the prognosis and save patient lives. We report a rare case of a 46 years old woman who underwent a hysterectomy and bilateral salpingo-oophorectomy 5 years earlier and presented with the right hemiparesis and whose CT scan and MRI of the brain showed cerebral lesions related to brain location of uterine leiomyosarcoma. The patient underwent surgery for gross total tumor resection, followed by adjuvant radiotherapy, and was doing well after surgery. Three months later she was admitted for recurrences and died after two months of palliative care.

Predicting survival and prognosis of postoperative breast cancer brain metastasis:a population-based retrospective analysis

Background:Breast cancer is one of the most common cancer in women and a proportion of patients experiences brain metastases with poor prognosis.The study aimed to construct a novel predictive clinical model to evaluate the overall survival(OS)of patients with postoperative brain metastasis of breast cancer(BCBM)and validate its effectiveness.Methods:From 2010 to 2020,a total of 310 female patients with BCBM were diagnosed in The Affiliated Cancer Hospital of Xinjiang Medical University,and they were randomly assigned to the training cohort and the validation cohort.Data of another 173 BCBM patients were collected from the Surveillance,Epidemiology,and End Results Program(SEER)database as an external validation cohort.In the training cohort,the least absolute shrinkage and selection operator(LASSO)Cox regression model was used to determine the fundamental clinical predictive indicators and the nomogram was constructed to predict OS.The model capability was assessed using receiver operating characteristic,C-index,and calibration curves.Kaplan-Meier survival analysis was performed to evaluate clinical effectiveness of the risk stratification system in the model.The accuracy and prediction capability of the model were verified using the validation and SEER cohorts.Results:LASSO Cox regression analysis revealed that lymph node metastasis,molecular subtype,tumor size,chemotherapy,radiotherapy,and lung metastasis were statistically significantly correlated with BCBM.The C-indexes of the survival nomogram in the training,validation,and SEER cohorts were 0.714,0.710,and 0.670,respectively,which showed good prediction capability.The calibration curves demonstrated that the nomogram had great forecast precision,and a dynamic diagram was drawn to increase the maneuverability of the results.The Risk Stratification System showed that the OS of lowrisk patients was considerably better than that of high-risk patients(P<0.001).Conclusion:The nomogram prediction model constructed in this study has a good predictive value,which can effectively evaluate the survival rate of patients with postoperative BCBM.

All-stage targeted therapy for the brain metastasis from triple-negative breast cancer

Brain metastasis is a common and serious complication of breast cancer,which is commonly associated with poor survival and prognosis.In particular,the treatment of brain metastasis from triplenegative breast cancer(BM-TNBC)has to face the distinct therapeutic challenges from tumor heterogeneity,circulating tumor cells(CTCs),blood-brain barrier(BBB)and blood-tumor barrier(BTB),which is in unmet clinical needs.Herein,combining with the advantages of synthetic and natural targeting moieties,we develop a“Y-shaped”peptide pVAP-decorated platelet-hybrid liposome drug delivery system to address the all-stage targeted drug delivery for the whole progression of BM-TNBC.Inherited from the activated platelet,the hybrid liposomes still retain the native affinity toward CTCs.Further,the peptide-mediated targeting to breast cancer cells and transport across BBB/BTB are demonstrated in vitro and in vivo.The resultant delivery platform significantly improves the drug accumulation both in orthotopic breast tumors and brain metastatic lesions,and eventually exhibits an outperformance in the inhibition of BM-TNBC compared with the free drug.Overall,this work provides a promising prospect for the comprehensive treatment of BMTNBC,which could be generalized to other cell types or used in imaging platforms in the future.

Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases:A case report

BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

Tumor microenvironment in lung cancer-derived brain metastasis

Brain metastasis(BM)is the leading cause of mortality in lung cancer patients.The process of BM(from initial primary tumor development,migration and intravasation,dissemination and survival in the bloodstream,extravasation,to colonization and growth to metastases)is a complex process for which few tumor cells complete the entire process.Recent research on BM of lung cancer has recently stressed the essential role of tumor microenvironment(TME)in assisting tumor cells in the completion of each BM step.This review summarizes recent studies regarding the effects of TME on tumor cells in the entire process of BM derived from lung cancer.The identification of vulnerable targets in the TME and their prospects to provide novel therapeutic opportunities are also discussed.

A novel PI3K inhibitor XH30 suppresses orthotopic glioblastoma and brain metastasis in mice models

Glioblastoma is carcinogenesis of glial cells in central nervous system and has the highest incidence among primary brain tumors.Brain metastasis,such as breast cancer and lung cancer,also leads to high mortality.The available medicines are limited due to blood-brain barrier.Abnormal activation of phosphatidylinositol 3-kinases(PI3 K)signaling pathway is prevalent in glioblastoma and metastatic tumors.Here,we characterized a 2-amino-4-methylquinazoline derivative XH30 as a potent PI3 K inhibitor with excellent anti-tumor activity against human glioblastoma.XH30 significantly repressed the proliferation of various brain cancer cells and decreased the phosphorylation of key proteins of PI3 K signaling pathway,induced cell cycle arrest in G1 phase as well.Additionally,XH30 inhibited the migration of glioma cells and blocked the activation of PI3 K pathway by interleukin-17 A(IL-17 A),which increased the migration of U87 MG.Oral administration of XH30 significantly suppressed the tumor growth in both subcutaneous and orthotopic tumor models.XH30 also repressed tumor growth in brain metastasis models of lung cancers.Moreover,XH30 reduced IL-17 A and its receptor IL-17 RA in vivo.These results indicate that XH30 might be a potential therapeutic drug candidate for glioblastoma migration and brain metastasis.