The influence of the coadministration of the p-glycoprotein modulator elacridar on the pharmacokinetics of lapatinib and its distribution in the brain and cerebrospinal fluid

Conclusion This study showed that elacridar influenced the pharmacokinetics of lapatinib. The inhibition of ABCB1 and ABCG2 transporters by elacridar substantially enhanced the penetration of lapatinib into the CSF and BT. The blocking of protein transporters could become indispensable in the treatment of patients with breast cancer and brain metastases.
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research

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Abstract The failure to treat and control the growth of metastases is the main cause of death in breast cancer (BC) patients. Compared to the traditional method of analyzing circulating tumor DNA (ctDNA), capturing intact circulating tumor cells (CTCs) allows us to more accurately characterize mutations and identify suitable targeted therapies. We used CellCollector to collect peripheral CTCs. Thirty metastatic breast cancer (MBC) patients were enrolled, and 17 were analyzed with next-generation sequencing (NGS) methods. Clinical characteristics were analyzed along with the CTCs enumeration and detection rates. Wh...
Source: Neoplasma - Category: Cancer & Oncology Authors: Tags: Neoplasma Source Type: research
(Northwestern University) When breast cancer spreads to the brain, the prognosis is grim. Patients only have about six months to live. Women with HER2-positive breast cancer tend to develop brain metastases in up to 55% of cases. Chemotherapy drugs targeting breast cancer cells in the brain aren't effective, because they can't cross the blood-brain-barrier. But a new combination therapy targeting breast cancer tumors in the brain dramatically decreased tumor size and increased survival in a preclinical study.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
In this study, we conducted a systematic analysis to determine the regulation of TUBB3 expression in breast cancer metastases to the brain and strategically target these metastases using vinorelbine (VRB), a drug approved by the U.S. Food and Drug Administration (FDA). We found that human epidermal growth factor receptor 2 (HER2) signaling regulates TUBB3 expression in both trastuzumab-sensitive and trastuzumab-resistant neoplastic cells. We further discovered that bromodomain and extra-terminal domain (BET) inhibition increases TUBB3 expression, rendering neoplastic cells more susceptible to apoptosis by VRB. Orthotopic x...
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research
Mechanisms driving tumor progression from less aggressive subtypes to more aggressive states represent key targets for therapy. We identified a subset of luminal A primary breast tumors that give rise to HER2-enriched (HER2E) subtype metastases, but remain clinically HER2 negative (cHER2–). By testing the unique genetic and transcriptomic features of these cases, we developed the hypothesis that FGFR4 likely participates in this subtype switching. To evaluate this, we developed 2 FGFR4 genomic signatures using a patient-derived xenograft (PDX) model treated with an FGFR4 inhibitor, which inhibited PDX growth in vivo....
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Conditions:   Breast Cancer;   Brain Metastases;   HER2-positive Breast Cancer;   CNS Disease Interventions:   Drug: Tucatinib;   Drug: Pembrolizumab;   Drug: Trastuzumab Sponsors:   Reva Basho;   Merck Sharp & Dohme Corp.;   Seattle Genetics, Inc. Not yet recruiting
Source: - Category: Research Source Type: clinical trials
Abstract Prior to the introduction of trastuzumab, the first targeted anti-HER2 agent, in 1998, patients diagnosed with HER2-positive breast cancer felt like they were being handed a death sentence. Despite treatment with aggressive chemotherapy, their tumors recurred faster, more often spread to brain and liver, and were associated with higher rates of death than HER2-negative tumors. HER2-positive breast cancer was also more prevalent in younger patients, making the diagnosis even more devastating. However, in the 1980s, cancer researcher Axel Ullrich, PhD, and oncologist Dennis Slamon, MD, PhD, recognized that ...
Source: Oncology (Williston Park, N.Y.) - Category: Cancer & Oncology Authors: Tags: Oncology (Williston Park) Source Type: research
Conclusion: Immuno-PET using anti-CEA/anti-IMP288 bispecific antibody, followed by 68Ga-IMP288, is a potentially sensitive theranostic imaging method for HER2-negative, CEA-positive metastatic breast cancer patients and warrants further research.
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Clinical Source Type: research
CONCLUSIONS: This study did not meet its primary endpoint. Abemaciclib was associated with an iCBR of 24% in patients with heavily pretreated HR+, HER2- MBC. Abemaciclib achieved therapeutic concentrations in BM tissue, far exceeding those necessary for CDK4 and CDK6 inhibition. Further studies are warranted, including assessing novel abemaciclib-based combinations. PMID: 32694159 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
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