her2 moa

The mitokine MOTS-c is a mitochondrially-encoded "exercise-mimetic peptide" expressed in multiple tissues, particularly skeletal muscles, which can be detected as a circulating hormone in the blood. MOTS-c mechanisms of action (MoA) involve insulin sensitization, enhanced glucose utilization, suppression of mitochondrial respiration, and targeting of the folate-AICAR-AMPK pathway. Although MOTS-c MoA largely overlap those of the anti-diabetic biguanide metformin, the putative regulatory actions of metformin on MOTS-c have not yet been evaluated in detail...

Although several antibody fragments and antibody fragment-fusion proteins produced in Escherichia coli ( E. coli ) are approved as therapeutics for various human diseases, a full-length monoclonal or a bispecific antibody produced in E. coli has not yet been approved. The past decade witnessed substantial progress in expression of full-length antibodies in the E. coli cytoplasm and periplasm, as well as in cell-free expression systems. The equivalency of E. coli -produced aglycosylated antibodies and their mammalian cell-produced counterparts, with respect to biochemical and biophysical properties, including antigen binding, in vitro and in vivo serum stability, pharmacokinetics, and in vivo serum half-life, has been demonstrated...

This case-control study is aimed to evaluate serum concentration of Cyclin-Dependent Kinase 6 (CDK6) and the genetic association between rs2237572 CDK6 gene and breast cancer (BC) in Iraq. To attain this goal, 80 patients with BC as cases and 80 healthy individuals as controls were included. Further, BC patients were sorted according to the molecular classification into four subtypes of Luminal A, Luminal B, Her2/neu enriched and TPN. Serum concentration of CDK6 enzyme, allelic and genotypic frequencies of rs2237572 CDK6 , and the occurrence of BC phenotype and its subtypes in the studied population were investigated...

Monoclonal antibodies (mAb) are a major component of cancer therapy. In this review, we summarize the different therapeutic mAbs that have been successfully developed against various tumor-expressed antigens and examine our current understanding of their different mechanisms of antitumor action. These mechanisms of action (MOA) largely center on the stimulation of different innate immune effector processes, which appear to be principally responsible for the efficacy of most unconjugated mAb therapies against cancer...

The HER2-specific monoclonal antibody (mAb), Trastuzumab, has been the mainstay of therapy for HER2+ breast cancers (BC) for ~20 years. However, its therapeutic mechanism of action (MOA) remains unclear, with antitumor responses to Trastuzumab remaining heterologous and metastatic HER2+ BC remaining incurable. Consequently, understanding its MOA could enable rational strategies to enhance its efficacy. Using both novel murine and human versions of Trastuzumab, we found its antitumor activity dependent on Fcγ-Receptor stimulation of tumor-associated-macrophages (TAM) and Antibody-Dependent-Cellular-Phagocytosis (ADCP), but not cytotoxicity (ADCC)...

BACKGROUND: SB3, a biosimilar of Herceptin® (trastuzumab, hereinafter referred to as reference product) is currently approved in the EU, Korea, Australia, the USA, and Brazil for the treatment of human epidermal growth factor receptor (HER) 2-positive early and metastatic breast cancer and HER2-positive metastatic gastric cancer. Previously, the biological similarity of SB3 to EU- or US-sourced reference product was assessed using various cell-based and binding assays. OBJECTIVE: In this paper, as a part of its similarity assessment, SB3 was evaluated for additional characteristics related to its molecular mechanism of action (MoA)...

To life scientists, one important feature offered by RNAseq, a next-generation sequencing tool used to estimate changes in gene expression levels, lies in its unprecedented resolution. It can score countable differences in transcript numbers among thousands of genes and between experimental groups, all at once. However, its high cost limits experimental designs to very small sample sizes, usually N = 3, which often results in statistically underpowered analysis and poor reproducibility. All these issues are compounded by the presence of experimental noise, which is harder to distinguish from instrumental error when sample sizes are limiting (e...

The development of antibody drug conjugates has provided enhanced potency to tumor-targeting antibodies by the addition of highly potent payloads. In the case of trastuzumab-DM1 (T-DM1), approved for the treatment of metastatic breast cancer, the addition of mertansine (DM1) to trastuzumab substantially increased progression-free survival. Despite these improvements, most patients eventually relapse due to complex mechanisms of resistance often associated with small molecule chemotherapeutics. Therefore, identifying payloads with different mechanisms of action (MOA) is critical for increasing the efficacy of targeted therapeutics and ultimately improving patient outcomes...

Emerging targeted therapies have shown benefits such as less toxicity and higher effectiveness in specific types of cancer treatment; however, the accessibility of these advantages may rely on correct identification of suitable patients, which remains highly immature. We assume that copy number profiles, being accessible genomic data via microarray techniques, can provide useful information regarding drug response and shed light on personalized therapy. Based on the mechanism of action (MOA) of trastuzumab in the HER2 signaling pathway, a Bayesian network model in which copy number alterations (CNAs) serve as latent parents modifying signal transduction is applied...