"Targeted therapy" AND breast

Breast cancer is one of the most diagnosed cancers worldwide. Precise diagnosis and subtyping have important significance for targeted therapy and prognosis prediction of breast cancer. Herein, we design a proximity-guaranteed DNA machine for accurate identification of breast cancer extracellular vesicles (EVs), which is beneficial to explore the subtype features of breast cancer. In our design, two proximity probes are located close on the same EV through specific recognition of coexisting surface biomarkers, thus being ligated with the help of click chemistry...

The prevention and management of cancer therapy-related cardiac dysfunction (CTRCD) have become increasingly important. Recent studies have revealed the crucial role of genetics in determining the susceptibility to development of CTRCD. We present a case of a 65-year-old woman with breast cancer who developed recurrent CTRCD following low-dose chemotherapy, despite lacking conventional cardiovascular risk factors. Her medical history included anthracycline-associated cardiomyopathy, and her condition deteriorated significantly after treatment with HER2-targeted therapies...

Resistance to MAPK inhibitors (MAPKi), the main cause of relapse in BRAF-mutant melanoma, is associated with the production of alternative BRAF mRNA isoforms (altBRAFs) in up to 30% of patients receiving BRAF inhibitor monotherapy. These altBRAFs have been described as being generated by alternative pre-mRNA splicing, and splicing modulation has been proposed as a therapeutic strategy to overcome resistance. In contrast, we report that altBRAFs are generated through genomic deletions. Using different in vitro models of altBRAF-mediated melanoma resistance, we demonstrate the production of altBRAFs exclusively from the BRAF V600E allele, correlating with corresponding genomic deletions...

BACKGROUND: Breast cancer stands as the most common malignancy among women globally and a leading cause of cancer-related mortality. Conventional treatments, such as surgery, hormone therapy, radiotherapy, chemotherapy, and small-molecule targeted therapy, often fall short of addressing the complexity and heterogeneity of certain breast cancer subtypes, leading to drug resistance and metastatic progression. Thus, the search for novel therapeutic targets and agents is imperative. Given their low toxicity and abundant variety, natural products and their derivatives are increasingly considered valuable sources for small-molecule anticancer drugs...

Triple Negative Breast Cancer (TNBC) is the most aggressive type of breast cancer (BC). Despite advances in the clinical management of TNBC, recurrence-related mortality remains a challenge. The stem-like phenotype of TNBC plays a significant role in the persistence of minimal disease residue after therapy. Individuals exhibiting stem-like characteristics are particularly prone to inducing malignant relapse accompanied by strong resistance. Therefore, stem-like traits have been broadly proposed as therapeutic vulnerabilities to treat TNBC and reduce recurrence...

Brain metastasis is a significant challenge for some breast cancer patients, marked by its aggressive nature, limited treatment options, and poor clinical outcomes. Immunotherapies have emerged as a promising avenue for brain metastasis treatment. B7-H3 (CD276) is an immune checkpoint molecule involved in T cell suppression, which is associated with poor survival in cancer patients. Given the increasing number of clinical trials using B7-H3 targeting CAR T cell therapies, we examined B7-H3 expression across breast cancer subtypes and in breast cancer brain metastases to assess its potential as an interventional target...

Gastroesophageal adenocarcinoma (GEA) is one of the principal causes of death related to cancer globally. Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase receptor which is found to be overexpressed or amplified in approximately 20% of GEA cases. In GEA, the identification of HER2-positive status is crucial to activate a specific anti-HER2 targeted therapy. The landmark ToGA trial demonstrated the superiority of adding trastuzumab to platinum-based chemotherapy, becoming the first-line standard of treatment...

Breast cancer (BCA) remains the leading cause of cancer-related mortality among women worldwide. This review delves into the therapeutic challenges of BCA, emphasizing the roles of interleukin-13 receptor α2 (IL-13Rα2) and erythropoietin-producing hepatocellular receptor A2 (EphA2) in tumor progression and resistance. Highlighting their overexpression in BCA, particularly in aggressive subtypes, such as Her-2-enriched and triple-negative breast cancer (TNBC), we discuss the potential of these receptors as targets for chimeric antigen receptor T-cell (CAR-T) therapies...

Targeted therapy has greatly improved the outlook for patients with spinal metastatic cancers. Scoring systems like the Tokuhashi or Tomita scores are commonly used to predict prognosis and inform surgical decisions, but they are outdated and fail to consider recent advancements. We aimed to investigate the current state of the literature and treatment options pertaining to advancements in targeted therapy compared to other forms of medical management for metastatic spinal tumors. This study represents the first comprehensive systematic review that encompasses the most common primary cancers that metastasize to the spine and evaluates the median overall survival (mOS) across five different medical treatment modalities as well as surgical intervention...

Topic modeling is a popular technique in machine learning and natural language processing, where a corpus of text documents is classified into themes or topics using word frequency analysis. This approach has proven successful in various biological data analysis applications, such as predicting cancer subtypes with high accuracy and identifying genes, enhancers, and stable cell types simultaneously from sparse single-cell epigenomics data. The advantage of using a topic model is that it not only serves as a clustering algorithm, but it can also explain clustering results by providing word probability distributions over topics...

Sperm-associated antigen 5 (SPAG5), also known as Astrin, was previously demonstrated as a biomarker for cellular resistance to major breast cancer therapies, including chemo-, endocrine- and targeted therapy. However, the contribution of SPAG5 to anthracycline- and taxane-based chemotherapy in triple-negative breast cancer (TNBC) remains controversial. In the present study, the SPAG5 knockout cell model was established by using clustered regularly interspaced palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system in MDA-MB-231 and BT549 TNBC cell lines...

As our grasp of cancer genomics deepens, we are steadily progressing towards the domain of precision medicine, where targeted therapy stands out as a revolutionary breakthrough in the landscape of cancer therapeutics. The fibroblast growth factor receptors (FGFR) pathway has been unveiled as a fundamental instigator in the pathophysiological mechanisms underlying breast carcinoma, paving the way for the exhilarating development of precision-targeted therapeutics. In the pursuit of exploring inhibitors that specifically target the FGFR signaling pathways, a multitude of kinase inhibitors targeting FGFR has been assiduously engineered to address the heterogeneous landscape of human malignancies...

Nectin-4 is a Ca2+ -independent immunoglobulin-like protein that exhibits significantly elevated expression in malignant tumors while maintaining extremely low levels in healthy adult tissues. In recent years, overexpression of Nectin-4 has been implicated in tumor occurrence and development of various cancers, including breast cancer, urothelial cancer, and lung cancer. In 2019, the Food and Drug Administration approved enfortumab vedotin, the first antibody-drug conjugate targeting Nectin-4, for the treatment of urothelial carcinoma...

Breast cancer is the most prevalent malignancy among women worldwide. Despite significant advances in treatment, it remains one of the leading causes of female mortality. The inability to effectively treat advanced and/or treatment-resistant breast cancer demonstrates the need to develop novel treatment strategies and targeted therapies. Centrosomes and their associated proteins have been shown to play key roles in the pathogenesis of breast cancer and thus represent promising targets for drug and biomarker development...

BACKGROUND: Most primary Triple Negative Breast Cancers (TNBCs) show amplification of the Epidermal Growth Factor Receptor (EGFR) gene, leading to increased protein expression. However, unlike other EGFR-driven cancers, targeting this receptor in TNBC yields inconsistent therapeutic responses. METHODS: To elucidate the underlying mechanisms of this variability, we employ cellular barcoding and single-cell transcriptomics to reconstruct the subclonal dynamics of EGFR-amplified TNBC cells in response to afatinib, a tyrosine kinase inhibitor (TKI) that irreversibly inhibits EGFR...

Cyclin-dependent kinase 7 (CDK7) serves as a pivotal regulator in orchestrating cellular cycle dynamics and gene transcriptional activity. Elevated expression levels of CDK7 have been ubiquitously documented across a spectrum of malignancies and have been concomitantly correlated with adverse clinical outcomes. This review delineates the biological roles of CDK7 and explicates the molecular pathways through which CDK7 exacerbates the oncogenic progression of breast cancer. Furthermore, we synthesize the extant literature to provide a comprehensive overview of the advancement of CDK7-specific small-molecule inhibitors, encapsulating both preclinical and clinical findings in breast cancer contexts...

Photothermal therapy (PTT) holds great promise as a cancer treatment modality by generating localized heat at the tumor site. Among various photothermal agents, gallium-based liquid metal (LM) has been widely used as a new photothermal-inducible metallic compound due to its structural transformability. To overcome limitations of random aggregation and dissipation of administrated LM particles into a human body, we developed LM-containing injectable composite hydrogel platforms capable of achieving spatiotemporal PTT and chemotherapy...

PURPOSE: Despite fibroblast growth factor receptor ( FGFR ) inhibitors being approved in tumor types with select FGFR rearrangements or gene mutations, amplifications of FGFR represent the most common FGFR alteration across malignancies. Subprotocol K1 (EAY131-K1) of the National Cancer Institute-MATCH platform trial was designed to evaluate the antitumor efficacy of the oral FGFR1-4 inhibitor, erdafitinib, in patients with tumors harboring FGFR1-4 amplification. METHODS: EAY131-K1 was an open-label, single-arm, phase II study with central confirmation of presence of FGFR1-4 amplification in tumors...

Targeted therapy of the highest globally incident breast cancer shall resolve the issue of off-target toxicity concurring with augmented killing of specific diseased cells. Thus, the goal of this study was to prepare a peptide-drug conjugate targeting elevated expression of HER2 receptors in breast cancer. Towards this, the rL-A9 peptide was conjugated with the chemotherapeutic drug doxorubicin (DOX) through a N-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) linker. The synthesized peptide-drug conjugate, rL-A9-DOX, was characterized by mass spectrometry...

Targeted therapies have improved outcomes for certain cancer subtypes, but cytotoxic chemotherapy remains a mainstay for triple-negative breast cancer (TNBC). The epithelial-to-mesenchymal transition (EMT) is a developmental program co-opted by cancer cells that promotes metastasis and chemoresistance. There are no therapeutic strategies specifically targeting mesenchymal-like cancer cells. We report that the US Food and Drug Administration (FDA)-approved chemotherapeutic eribulin induces ZEB1-SWI/SNF-directed chromatin remodeling to reverse EMT that curtails the metastatic propensity of TNBC preclinical models...