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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: Patients who have had an axillary lymph node dissection and limited node-positive disease may be candidates for treatment with APBI. Further research is ultimately needed to better define specific criteria for APBI in node-positive patients.
Source: American Journal of Clinical Oncology - Category: Cancer & Oncology Tags: Original Articles: Breast Source Type: research
CONCLUSION: Postmenopausal women with HR+/HER2- mBC who have previously failed an NSAI and received palbociclib+fulvestrant, everolimus+AI or everolimus+fulvestrant had longer PFS compared to those who received fulvestrant or AI alone. PMID: 29781326 [PubMed - as supplied by publisher]
Source: Current Medical Research and Opinion - Category: Research Tags: Curr Med Res Opin Source Type: research
M árcio Debiasi, Carisi A. Polanczyk, Patrícia Ziegelmann, Carlos Barrios, Hongyuan Cao, James J. Dignam, Paul Goss, Brittany Bychkovsky, Dianne M. Finkelstein, Rodrigo S. Guindalini, Paulo Filho, Caroline Albuquerque, Tomás Reinert, Evandro de Azambuja, Olufunmilayo Olopade
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, we identified no SNPs significantly associated with NAC. The observation, in a hypothesis-generating GWAS, of an SNP in CDKAL1 associated with pCR in the bevacizumab arm of both B-40 and GeparQuinto requires further validation and study.
Source: Pharmacogenetics and Genomics - Category: Genetics & Stem Cells Tags: Short Communication Source Type: research
Conclusion Expression of p95-HER2 in HER2-positive BC patients is significantly associated with negative hormonal receptors expression, high Ki-67 expression, presence of visceral metastases and worse overall survival. A larger study is required to confirm its association with different prognostic factors and its effect on survival.
Source: Journal of the Egyptian National Cancer Institute - Category: Cancer & Oncology Source Type: research
Abstract PURPOSE: The purpose of this work was to assess the truncated form of human epidermal growth factor receptor 2 (HER2) such as p95-HER2 expression in HER2-positive breast cancer (BC) patients who developed metastatic disease after adjuvant treatment with a trastuzumab-containing regimen. PATIENTS AND METHODS: Thirty-two histologically diagnosed HER2-positive BC patients who developed distant failure after treatment with trastuzumab-based chemotherapy (CT) regimen as an adjuvant therapy were included in the study. Immunohistochemistry (IHC) method was used to analyze p95-HER2 expression in the formalin...
Source: J Egypt Natl Canc In... - Category: Cancer & Oncology Authors: Tags: J Egypt Natl Canc Inst Source Type: research
ConclusionElevated dNLR appears to be an adverse prognostic factor in hormone receptor-negative early breast cancer.Trial registrationEudraCT: 2005-003108-12 (retrospectively registered 28/06/2005). ClinicalTrials.gov Identifier: NCT00129922 (retrospectively registered 10/08/2005). Results of this study were presented in part at the 2016 ESMO conference October 7 –11, 2016, Copenhagen, Denmark (oral presentation).
Source: Clinical and Translational Oncology - Category: Cancer & Oncology Source Type: research
Authors: Cvetanovic A, Filipovic S, Zivkovic N, Popovic L, Kostic M, Djordjevic M, Karanikolic A, Krtinic D Abstract PURPOSE: The purpose of this study was to determinate disease-free interval (DFI) and overall survival (OS) in HER2-positive breast cancer patients who received adjuvant trastuzumab at the University Clinic of Nis, Serbia, and to investigate the influence of clinicopathological and biological characteristics of the tumor on prognosis. The second aim was to determinate the most frequent cause for the treatment discontinuation, recurrence rate, as well as the site of most common localization of the fir...
Source: Journal of B.U.ON. - Category: Cancer & Oncology Tags: J BUON Source Type: research
Condition:   HER2-positive Breast Cancer Interventions:   Other: RNA sequencing;   Other: Transcriptome analysis;   Drug: Trastuzumab;   Drug: Chemotherapy Sponsors:   Omicsway Corporation;   Oncobox Ltd., Russia;   Vitamed, Russia;   Republican Oncological Dispensary of Karelia Republic, Russia Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
More News: Breast Cancer | Cancer | Cancer & Oncology | Chemotherapy | Drugs & Pharmacology | HER2 | Herceptin