Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Recent translational research: antiangiogenic therapy for breast cancer - where do we stand?

ABSTRACT: The central importance of angiogenesis and our understanding of how new blood vessels are formed have led to the development of novel antiangiogenic therapies. Although the number of agents in development has grown exponentially, only one phase III trial in breast cancer has been completed. In that study the addition of bevacizumab to capecitabine did not extend the progression-free survival of patients with refractory disease as compared with capecitabine monotherapy. Early enthusiasm for antiangiogenic therapy must give way to clinical reality. Our challenge now is to exploit better the activity of antiangiogenic agents seen in the early clinical studies.

SUBMITTER: Miller KD

PROVIDER: S-EPMC400679 | biostudies-literature | 2004

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Recent translational research: antiangiogenic therapy for breast cancer - where do we stand?

Miller Kathy D KD

Breast cancer research : BCR 20040318 3

The central importance of angiogenesis and our understanding of how new blood vessels are formed have led to the development of novel antiangiogenic therapies. Although the number of agents in development has grown exponentially, only one phase III trial in breast cancer has been completed. In that study the addition of bevacizumab to capecitabine did not extend the progression-free survival of patients with refractory disease as compared with capecitabine monotherapy. Early enthusiasm for antia ...[more]

PMID: 15084233

Similar Datasets

Antiangiogenic therapy for breast cancer.

Project description:Angiogenesis is an important component of cancer growth, invasion and metastasis. Therefore, inhibition of angiogenesis is an attractive strategy for treatment of cancer. We describe existing clinical trials of antiangiogenic agents and the challenges facing the clinical development and optimal use of these agents for the treatment of breast cancer. Currently, the most promising approach has been the use of bevacizumab, a humanized monoclonal antibody directed against the most potent pro-angiogenic factor, vascular endothelial growth factor (VEGF). Small molecular inhibitors of VEGF tyrosine kinase activity, such as sorafenib, appear promising. While, the role of sunitinib and inhibitors of mammalian target of rapamycin (mTOR) in breast cancer has to be defined. Several unanswered questions remain, such as choice of drug(s), optimal duration of therapy and patient selection criteria.

| S-EPMC3096961 | biostudies-literature

Reappraising antiangiogenic therapy for breast cancer.

Project description:Phase III trials of antiangiogenic drugs for metastatic breast cancer have either had only limited success, e.g. the monoclonal anti-VEGF antibody bevacizumab when used with various conventional chemotherapy regimens, or have failed altogether, e.g. the small molecule oral tyrosine kinase inhibitor (TKI) sunitinib. No phase III trial has yet demonstrated an overall survival benefit and the progression free survival (PFS) benefits, when attained with bevacizumab are short, with perhaps one exception. Together, these results call for a reappraisal of using antiangiogenic drugs for breast cancer and possible strategies to improve their efficacy. Among the reasons to help explain the limited benefits observed thus far include the possibility that angiogenesis may not be a major driver of breast cancer growth, compared to some other types of cancer; that acquired resistance may develop rapidly to VEGF-pathway targeting antiangiogenic drugs, in part due to angiogenic growth factor redundancy; that optimal chemotherapy regimens have not been used in conjunction with an antiangiogenic drug; and that antiangiogenic drugs may secondarily aggravate biologic aggressiveness of the tumors, thereby reducing their overall efficacy after inducing an initial benefit. Several possible strategies are discussed for improving the efficacy of antiangiogenic drugs, including combination with different chemotherapy regimens, e.g. long term and less toxic metronomic chemotherapy protocols; validation of predictive biomarkers to individualize patient therapy; development of improved preclinical therapy models, e.g. involving advanced metastatic breast cancer, and combination with other types of anti-cancer agents especially biologies such as trastuzumab for Her2-positive breast cancer. Reasons for the current concern regarding use of antiangiogenic drug treatments for early stage cancers, including breast cancer, are also discussed.

| S-EPMC4540338 | biostudies-literature

Recent Advancements of Nanomedicine towards Antiangiogenic Therapy in Cancer.

Project description:Angiogenesis is a process of generation of de-novo blood vessels from already existing vasculature. It has a crucial role in different physiological process including wound healing, embryonic development, and tumor growth. The methods by which therapeutic drugs inhibit tumor angiogenesis are termed as anti-angiogenesis cancer therapy. Developments of angiogenic inhibiting drugs have various limitations causing a barrier for successful treatment of cancer, where angiogenesis plays an important role. In this context, investigators developed novel strategies using nanotechnological approaches that have demonstrated inherent antiangiogenic properties or used for the delivery of antiangiogenic agents in a targeted manner. In this present article, we decisively highlight the recent developments of various nanoparticles (NPs) including liposomes, lipid NPs, protein NPs, polymer NPs, inorganic NPs, viral and bio-inspired NPs for potential application in antiangiogenic cancer therapy. Additionally, the clinical perspectives, challenges of nanomedicine, and future perspectives are briefly analyzed.

| S-EPMC7013812 | biostudies-literature

Recent developments and translational aspects in targeted therapy for metastatic breast cancer.

Project description:Biologically distinct subtypes of metastatic breast cancer (MBC) have been defined by multiple efforts in recent years, showing broad heterogeneity at the molecular level of disease. Throughout this endeavour, oncogenic drivers within MBC were identified as potential therapeutic targets. With recent results from clinical trials targeting these well-known cancer-promoting pathways, this review is trying to elucidate as well as summarise current new therapeutic aspects in MBC and shed light on translational aspects within this entity.

| S-EPMC5070263 | biostudies-literature

Recent translational research: microarray expression profiling of breast cancer--beyond classification and prognostic markers?

Project description:Genomic expression profiling has greatly improved our ability to subclassify human breast cancers according to shared molecular characteristics and clinical behavior. The logical next question is whether this technology will be similarly useful for identifying the dominant signaling pathways that drive tumor initiation and progression within each breast cancer subtype. A major challenge will be to integrate data generated from the experimental manipulation of model systems with expression profiles obtained from primary tumors. We highlight some recent progress and discuss several obstacles in the use of expression profiling to identify pathway signatures in human breast cancer.

| S-EPMC549178 | biostudies-literature

Circulating Carbonic Anhydrase IX and Antiangiogenic Therapy in Breast Cancer.

Project description:Carbonic anhydrase IX (CAIX) is a hypoxia regulated metalloenzyme integral to maintaining cellular pH. Increased CAIX expression is associated with poor prognosis in breast cancer. To explore CAIX as a biomarker for breast cancer therapies, we measured plasma CAIX levels in healthy control subjects and in breast cancer patients.In control subjects we evaluated plasma CAIX stability via commercially available ELISA. We then similarly quantified plasma CAIX levels in (1) locally advanced breast cancer (LABC) patients treated with neoadjuvant paclitaxel + sunitinib (T + S) followed by doxorubicin and cyclophosphamide (AC); (2) metastatic breast cancer (MBC) patients treated with systemic chemotherapy.Plasma CAIX levels were stable at room temperature for at least 48 hours in control subjects. Mean baseline plasma CAIX levels were lower in controls compared to patients with LABC or MBC. In LABC, CAIX levels rose significantly in response to administration of antiangiogenic therapy (T + S) (p = 0.02) but not AC (p = 0.37). In patients with MBC treated without an antiangiogenic agent CAIX levels did not change with therapy.Our results suggest that CAIX may be an easily obtained, stable measure of tumor associated hypoxia as well as a useful pharmacodynamic biomarker for antiangiogenic therapy.

| S-EPMC4749816 | biostudies-literature

Recent advances in neoadjuvant therapy for breast cancer.

Project description:Neoadjuvant trials for early breast cancer have accelerated the identification of novel active agents, enabling streamlined conduct of registration trials with fewer subjects. Measurement of neoadjuvant drug effects has also enabled the identification of patients with high risk of distant recurrence and has justified development of additional adjuvant approaches to improve outcomes. Neoadjuvant evaluation of new drugs was significantly improved by the introduction of pathologic complete response (pCR) rate as a quantitative surrogate endpoint for distant disease-free survival (DDFS) and event free survival (EFS). The neoadjuvant phase 2 platform trial I-SPY 2 simultaneously tests multiple drugs across multiple breast cancer subtypes using Bayesian methods of adaptive randomization for assessment of drug efficacy. In addition to the pCR endpoint, the I-SPY 2 trial has demonstrated that the residual cancer burden (RCB) score measures gradations of tumor response that correlate with DDFS and EFS across treatments and subtypes. For HER2-positive and triple-negative breast cancers that have failed to attain pCR with neoadjuvant chemotherapy (NAC), effective modifications of adjuvant treatment have improved outcomes and changed the standard of care for these subtypes. Neoadjuvant therapy is therefore preferred for stage II and III, as well as some stage I, HER2-positive and triple-negative tumors. Neoadjuvant endocrine therapy (NET) strategies have also emerged from innovative trials for stage II and III estrogen receptor (ER)-positive/HER2-negative tumors, as in the ALTERNATE trial. From neoadjuvant trials, opportunities have emerged to de-escalate therapy on the basis of metrics of response to chemotherapy or hormonal therapy. Neoadjuvant therapy for early breast cancer is therefore emerging as a promising approach to accelerate new drug development, optimize treatment strategies, and (where appropriate) de-escalate neoadjuvant therapy.

| S-EPMC7894264 | biostudies-literature

Recent advancements of antiangiogenic combination therapies in ovarian cancer.

Project description:Ovarian cancer is a deadly malignancy with a growing therapeutic armamentarium, though achieving sustained benefit in the clinic remains largely elusive. Through biomarker and genetic analysis, several pathways of resistance and sensitivity to commonly used therapeutics have been identified, expanding the potential of identifying unique drug combinations and indicating new directions for improving clinical outcomes. Here, we review the mechanisms of angiogenic response and antiangiogenic therapy in ovarian cancer, as well as the interactions it exhibits with the immune and DNA damage response pathways. We discuss results from clinical trials examining the combinations of antiangiogenics, PARP inhibitors, and immune checkpoint inhibitors are also discussed, as well as several ongoing trials.

| S-EPMC8217312 | biostudies-literature

Targeting evasion from Antiangiogenic therapy

Project description:Abstract: Therapeutic targeting of tumor angiogenesis with VEGF inhibitors results in demonstrable but transitory efficacy in certain human tumors and mouse models of cancer, limited by unconventional forms of adaptive/evasive resistance. In one such mouse model, potent angiogenesis inhibitors elicit compartmental reorganization of cancer cells around remaining blood vessels. The glucose and lactate transporters GLUT1 and MCT4 are induced in distal hypoxic cells in a HIF1α-dependent fashion, indicative of glycolysis. Tumor cells proximal to blood vessels instead express the lactate transporter MCT1, and p-S6, the latter reflecting mTOR signaling. Normoxic cancer cells import and metabolize lactate, resulting in upregulation of mTOR signaling via glutamine metabolism enhanced by lactate catabolism. Thus metabolic symbiosis is established in the face of angiogenesis inhibition, whereby hypoxic cancer cells import glucose and export lactate, while normoxic cells import and catabolize lactate. mTOR signaling inhibition disrupts this metabolic symbiosis, associated with upregulation of the glucose transporter GLUT2.

2016-07-15 | GSE80436 | GEO

International Web-based consultation on priorities for translational breast cancer research.

Project description:BackgroundLarge numbers of translational breast cancer research topics have been completed or are underway, but they differ widely in their immediate and/or future importance to clinical management. We therefore conducted an international Web-based consultation of breast cancer professionals to identify the topics most widely considered to be of highest priority.MethodsPotential participants were contacted via two large e-mail databases and asked to register, at a Web site, the issues that they felt to be of highest priority. Four hundred nine questions were reduced by a steering committee to 70 unique issues, and registrants were asked to select the 6 questions they considered to be the most important.ResultsVotes were recorded from 420 voters (2,520 votes) from 48 countries, with 48% of voters coming from North America. Half of the voters identified themselves as clinicians, with the remainder being academics, research scientists, or pathologists. The highest priority was to identify molecular signatures to select patients who could be spared chemotherapy, which gained about 50% more votes than the second topic and was consistently voted top by voters in North America, Europe, and the rest of the world. Research scientists voted the determination of the role of stem cells in breast cancer development, progression, and treatment sensitivity as the most important issue, but this was considered the sixth priority for clinicians and fourth overall.ConclusionThis exercise may bring a greater focus of research resources onto issues voted as top priorities.

| S-EPMC2246180 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data