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: In our experience, the use of odx was concordant with published recommendations and had a positive cost impact. PMID: 30111977 [PubMed - in process]
Source: Current Oncology - Category: Cancer & Oncology Tags: Curr Oncol Source Type: research
SummaryIn the areas of chemotherapy, targeted therapy and immunotherapy, several interesting and clinically relevant data were presented at the 2017 San Antonio Breast Cancer Symposium (SABCS). This short review focuses on dose-dense and/or sequential administration of adjuvant chemotherapy, provides an update on targeted therapies for HER2-positive and triple-negative breast cancer and summarizes new results in the field of immunotherapy.
Source: Memo - Magazine of European Medical Oncology - Category: Cancer & Oncology Source Type: research
ConclusionA considerable proportion of premenopausal women with aBC received first- and second-line chemotherapy, which appears inconsistent with current clinical guidelines. The observed treatment heterogeneity points to a lack real-world consensus on the management of premenopausal women with HR+/HER2 − aBC.FundingNovartis Pharmaceuticals Corporation.
Source: Advances in Therapy - Category: Drugs & Pharmacology Source Type: research
Conclusions: Here, we showed that functional cooperative miRNAs effectively suppressed erbB3 expression. This novel approach targeting of HER3 was able to enhance the therapeutic efficacy of trastuzumab and paclitaxel against HER2-overexpressing breast cancer. PMID: 30093840 [PubMed]
Source: Biological Procedures Online - Category: Molecular Biology Authors: Tags: Biol Proced Online Source Type: research
Conclusions: Our study showed that APOBEC3B mRNA expression correlated with sensitivity to NAC in breast cancer patients. In contrast to previous studies, APOBEC3B mRNA expression was not associated with breast cancer prognosis in patients receiving NAC. PMID: 30093965 [PubMed]
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Condition:   Malignant Neoplasm of Breast Interventions:   Drug: M7824 - patients with Stage II or III HER2+ breast cancer;   Drug: Chemotherapy Sponsors:   M.D. Anderson Cancer Center;   EMD Serono Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Condition:   Malignant Neoplasm of Breast Interventions:   Drug: M7824;   Drug: Chemotherapy Sponsors:   M.D. Anderson Cancer Center;   EMD Serono Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Condition:   Malignant Neoplasm of Breast Interventions:   Drug: M7824 - patients with Stage II or III HER2+ breast cancer;   Drug: Chemotherapy Sponsors:   M.D. Anderson Cancer Center;   EMD Serono Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Condition:   Malignant Neoplasm of Breast Interventions:   Drug: M7824;   Drug: Chemotherapy Sponsors:   M.D. Anderson Cancer Center;   EMD Serono Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Condition:   Malignant Neoplasm of Breast Interventions:   Drug: M7824 - patients with Stage II or III HER2+ breast cancer;   Drug: Chemotherapy Sponsors:   M.D. Anderson Cancer Center;   EMD Serono Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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