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Doxorubicin conjugated with a trastuzumab epitope and an MMP-2 sensitive peptide linker for the treatment of HER2-positive breast cancer.

Doxorubicin conjugated with a trastuzumab epitope and an MMP-2 sensitive peptide linker for the treatment of HER2-positive breast cancer. Drug Deliv. 2018 Nov;25(1):448-460 Authors: You Y, Xu Z, Chen Y Abstract HER2-positive breast cancer correlates with more aggressive tumor growth, a poorer prognosis and reduced overall survival. Currently, trastuzumab (Herceptin), which is an anti-HER2 antibody, is one of the key drugs. There is evidence indicating that conjugation of trastuzumab with chemotherapy drugs, such as doxorubicin (DOX), for multiple targets could be more effective. However, incomplete penetration into tumors has been noted for those conjugates. Compared to an antibody, peptides may represent an attractive alternative. For HER2, a similar potency has been observed for a 12-amino-acid anti-HER2 peptide mimetic YCDGFYACYMDV-NH2 (AHNP, disulfide-bridged) and full-length trastuzumab. Thus, a peptide, GPLGLAGDDYCDGFYACYMDV-NH2, which consists of AHNP and an MMP-2 cleavable linker GPLGLAGDD, was first designed, followed by conjugation with DOX via a glycine residue at the N-terminus to form a novel DOX-peptide conjugate MAHNP-DOX. Using HER2-positive human breast cancer cells BT474 and SKBR3 as in vitro model systems and nude mice with BT474 xenografts as an in vivo model, this conjugate was comprehensively characterized, and its efficacy was evaluated and compared with that of free DOX. As a result, MAHNP-DOX demonstrated a much lower in vitro IC5...
Source: Drug Delivery - Category: Drugs & Pharmacology Tags: Drug Deliv Source Type: research

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CONCLUSIONS: This study confirmed the therapeutic impact of lapatinib, trastuzumab, and paclitaxel therapy for each ER- and ER+ subgroup of HER2+ patients. Development of further strategies and tools is required, particularly for luminal HER2 disease. PMID: 29445928 [PubMed - as supplied by publisher]
Source: Breast Cancer - Category: Cancer & Oncology Authors: Tags: Breast Cancer Source Type: research
(European Organisation for Research and Treatment of Cancer) A trial published todayin The Lancet Oncology, shows that, in older patients with HER2 positive metastatic breast cancer (an aggressive breast cancer subtype where the cancer has spread to other parts of the body), a combination of a 'soft' chemotherapy with antiHER2 therapy is highly active and has low toxicity, important in a frail population.
Source: EurekAlert! - Social and Behavioral Science - Category: International Medicine & Public Health Source Type: news
This article reviews the principal attempts of immune-modulation or immune therapy in metastatic breast cancer. It considers their rationale and reports on results from the relevant key clinical trials. Immune-modulatory or immune-stimulating cytokines used alone or combined with conventional therapies is among the principal approaches of immune manipulation in breast cancer. As this issue was recently reviewed by us, the aim of the current article is to discuss our updated and unpublished data on this topic. Overall survival in luminal (28 patients) and non-luminal (9 patients) molecular subtypes is 91 and 59 months respe...
Source: Current Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Med Chem Source Type: research
CONCLUSIONS: Tailored locoregional and systemic therapy resulted in low incidence of failure in these octogenarians with high-risk cancers with low morbidity. Modern adjuvant therapies should be considered for elderly women with high-risk cancers in the absence of significant comorbidities. PMID: 29427213 [PubMed - as supplied by publisher]
Source: Ann Oncol - Category: Cancer & Oncology Authors: Tags: Ann Surg Oncol Source Type: research
By BISHAL GYAWALI, MD Why conduct post approval studies at all? Atezolizumab previously received accelerated approval in second-line metastatic or advanced urothelial cancer based on response rates from a single arm trial. The results of post approval confirmatory phase 3 are now published and demonstrate that atezolizumab did not improve survival versus chemotherapy (11.1 v 10.6 months, HR 0.87, p = 0.41). The concept of accelerated approval is to grant early and conditional approval and access to drugs in diseases of unmet need, and that the decision to fully approve or revoke be made based ...
Source: The Health Care Blog - Category: Consumer Health News Authors: Tags: Uncategorized Source Type: blogs
In conclusion, our data shows that NVP-AUY922 displays potent anti-cancer activity in HER2-positive and trastuzumab-resistant breast cancer cells, and supports further testing of NVP-AUY922 in patients with HER2-positive breast cancer.
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research
AbstractPurposeThe purpose of this two-cohort Phase II trial was to estimate the pathologic complete response (pCR: ypT0/is ypN0) rate when trastuzumab plus pertuzumab are administered concurrently during both the taxane and anthracycline phases of paclitaxel and 5-fluorouracil/epirubicin/cyclophosphamide (FEC) neoadjuvant chemotherapy.MethodsThe pCR rates were assessed separately in hormone receptor (HR) positive and negative cases following Simon ’s two-stage design, aiming to detect a 20% absolute improvement in pCR rates from 50 to 70 and 70 to 90% in the HR-positive and HR-`negative cohorts, respectively.Results...
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
ConclusionsOur preliminary observations suggest that the EphA2-targeted MSN delivery system may provide a strategy for enhancing delivery of therapeutic agents to breast cancer cells expressing EphA2, and potentially reduce toxicity while enhancing therapeutic efficacy.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
Authors: Richter H, Hennigs A, Schaefgen B, Hahn M, Blohmer JU, Kümmel S, Kühn T, Thill M, Friedrichs K, Sohn C, Golatta M, Heil J Abstract The likelihood of pathological complete remission (pCR) of breast cancer following neoadjuvant chemotherapy (NACT) is increasing; most of all in the triple negative and HER2 positive tumour subgroups. The question thus arises whether or not breast surgery is necessary when there is complete remission after NACT, and whether it provides any improvement of the oncological treatment result when tumour is no longer detectable. Avoiding surgery and possibly even radiothera...
Source: Geburtshilfe und Frauenheilkunde - Category: OBGYN Tags: Geburtshilfe Frauenheilkd Source Type: research
AbstractAs its incidence increases with age, breast cancer in elderly patients takes on a growing importance in clinical oncology practice. Management decisions are challenging because there is a lack of high-quality evidence in this heterogeneous population. Epidemiological studies have shown that breast cancer mortality does not decrease substantially in the older population compared with younger adults. Recent data suggest a phenotype somewhat different from that of younger patients, also confirmed at the molecular level. Breast cancer biology has been incompletely deciphered in this age group. New therapeutic agents co...
Source: Drugs and Aging - Category: Geriatrics Source Type: research
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