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Chemopreventive Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Oleic acid consumption has been associated with a decreased risk of breast cancer, and an article in Annals of Oncology in 2005 was one of the first to suggest that ingesting olive oil may reduce the risk of breast cancer. This finding was based on a study in which oleic acid was found to inhibit the growth of cancer cells growing in vitro and prevent over-expression of the oncogene HER2/neu, which is known to be a significant contributor to the development and management of certain types of breast tumors. Over-expression of HER2/neu is seen in about 20% of breast cancers and is associated with an unfavorable clinical outcome and resistance to chemotherapy. Using human breast cancer models expressing high levels of HER2/neu, it was demonstrated that oleic acid suppresses over-expression of the oncogene, suggesting that dietary supplementation with this fatty acid could play a role in the prevention or management of certain types of breast cancer. In support of this, further in vitro studies have shown that oleic acid can make HER2/neu over-expressing cancer cells more sensitive to the effects of clinically relevant concentrations of trastuzumab (HerceptinTM). Based on this, it is possible that oleic acid may also be synergistic with other therapies directed at HER2/neu, and it has been suggested that dietary counseling could help delay or prevent trastuzumab resistance in patients with this type of breast cancer.
Nanomaterials for Theranostics: Recent Advances and Future Challenges *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Eun-Kyung Lim, Taekhoon Kim, Soonmyung Paik, Seungjoo Haam, Yong-Min Huh, Kwangyeol Lee
Cancer cell targeting using antibody or cRGD was also applicable for silica-based drug carrier. Mou et al. conjugated anti-HER2/neu mAb to green fluorescent dye-loaded mesoporous silica nanoparticles (Her-Dye@MSN) through a PEG spacer [857]. They examined their targeting properties toward HER2/neu overexpressing breast cancer cells and their internalization into the cells. Her-Dye@MSN nanoparticles exhibited a high targeting efficiency, and the specific targeting capability was strongly affected by the mAb density on the Her-Dye@MSN. Nanoparticles with a high amount of Herceptin showed greater selectivity and a higher targeting efficiency toward BT-474. Herceptin-functionalized mesoporous silica nanoparticles were internalized into BT-474 cells via receptor-mediated endocytosis, and some of them escaped from the endosome to the cytosol. On the other hand, Lo et al. utilized cRGD to target cancer cells that overexpress αvβ3 integrin [858]. The photosensitizer (Pd-meso-tetra(4-carboxyphenyl) porphyrin, PdTPP)-loaded mesoporous silica nanoparticles were target selectively delivered into U87-MG glioblastoma and could kill the cancer cells via PDT (Fig. 16.46).
Predictive Markers for Targeted Breast Cancer Treatment
Published in Brian Leyland-Jones, Pharmacogenetics of Breast Cancer, 2020
Hans Christian B. Pedersen, John M. S. Bartlett
HER2/neu or human epidermal growth factor receptor 2, a product of the protooncogene HER2 first discovered in 1985, belongs to the HER family of tyrosine kinase receptors (16–18). Numerous studies have documented HER2/neu- positive breast cancers display more aggressive disease and shortened disease- free survival (19). Using recombinant technologies, trastuzumab (Herceptin®, Genentech, South San Francisco, California, U.S.), a monoclonal immunoglobulin G1 class, humanized murine antibody, was developed to specifically target patients with breast cancer that overexpressed the HER2/neu protein (20,21). Clinical trials demonstrated the efficiency of trastuzumab for treating metastatic breast cancers and subsequent trials in combination therapy (21–25) for HER2 positive disease. Again, HER2/neu, like ERα, is more predictive of which patients will not respond to treatment.
Trastuzumab-deruxtecan: an investigational agent for the treatment of HER2-positive breast cancer
Published in Expert Opinion on Investigational Drugs, 2020
Breast cancer is the most common malignant disease in women worldwide [1]. The term breast cancer encompasses a heterogeneous group of malignancies differentiated by underlying biology, clinical behavior, and treatment strategies [2,3]. Approximately two-thirds of all breast cancers belong to the luminal subtype as defined by the expression of hormone receptors (estrogen and/or progesterone receptor), making antihormonal interventions the mainstay of treatment [4–7]. HER2-positive breast cancer is defined by the overexpression of the transmembrane HER2 (Human-EGFR-Related 2) receptor as defined by immunohistochemistry or by the amplification of the HER2/neu gene located on chromosome 17. HER2/neu was first described in 1984 and as early as 1987, Slamon et al. identified HER2-positive breast cancer as a high-risk disease subtype [8,9]. The prognosis of these patients has dramatically changed with the introduction of HER2-directed targeted therapies [10,11]. Finally, breast tumors lacking expression of the hormone receptors and HER2 overexpression or HER2/neu gene-amplification are summarized by the term triple-negative breast cancer (TNBC) which is, however, a heterogeneous group of malignancies in itself [12–14].
CAR T cells and checkpoint inhibition for the treatment of glioblastoma
Published in Expert Opinion on Biological Therapy, 2020
Steven H. Shen, Karolina Woroniecka, Andrew B. Barbour, Peter E. Fecci, Luis Sanchez-Perez, John H. Sampson
HER2 (also commonly referred to as HER2/Neu or ERBB2) is an orphan receptor member of the EGFR family. While commonly found in many tissues during adulthood, HER2 expression is absent in both neuronal and glial tissue. HER2 is a proto-oncogene that is activated and expressed at high levels in primary malignant brain tumors such as GBM. The expression of HER2 can be found in 20–80% of GBMs, with a modest degree of heterogeneity; however, due to its absence in normal brain tissue, it has become an attractive target for CAR T cell therapy [31,32]. Developed by Ahmed et al., second-generation HER2-specific CAR T cells aim to target primary GBM stem cells. When cultured in vitro or infused intracranially into mice with primary GBM xenografts, HER2 CAR T cells were able to eradicate autologous GBM stem cells [33]. GBM cells that were HER2 negative, however, were not killed [33].
Incorporation of p-53 mutation status and Ki-67 proliferating index in classifying Her2-neu positive gastric adenocarcinoma
Published in Libyan Journal of Medicine, 2018
Ayesha Ahmed, Dalal M. Al-Tamimi
Her2-neu overexpression has a pathogenetic, therapeutic and prognostic role in gastric cancer. Evaluation of Her2-neu overexpression for targeted therapies is currently the mainstay treatment strategy [3]. Her2-neu as a negative prognostic parameter has established a strong foot holds in breast cancer. The ToGA trial (Trastuzumab for Gastric Cancer) attributed a similar status to Her2-neu in gastric cancer, yet no unanimous consensus has evolved so far in this regards till now [4,5]. Prognostic factors defined for the staging and therapeutic interventions in gastric cancer are imprecise as patients with similar parameters actually prove to be at different levels clinically, attributing a controversial prognostic status to Her2-neu overexpressivity [6].