Trastuzumab: More than a Guide in HER2-Positive Cancer Nanomedicine

Abstract

HER2 overexpression, which occurs in a fifth of diagnosed breast cancers as well as in other types of solid tumors, has been traditionally linked to greater aggressiveness. Nevertheless, the clinical introduction of trastuzumab has helped to improve HER2-positive patients’ outcomes. As a consequence, nanotechnology has taken advantage of the beneficial effects of the administration of this antibody and has employed it to develop HER2-targeting nanomedicines with promising therapeutic activity and limited toxicity. In this review, the molecular pathways that could be responsible for trastuzumab antitumor activity will be briefly summarized. In addition, since the conjugation strategies that are followed to develop targeting nanomedicines are essential to maintaining their efficacy and tolerability, the ones most employed to decorate drug-loaded nanoparticles and liposomes with trastuzumab will be discussed here. Thus, the advantages and disadvantages of performing this trastuzumab conjugation through adsorption or covalent bindings (through carbodiimide, maleimide, and click-chemistry) will be described, and several examples of targeting nanovehicles developed following these strategies will be commented on. Moreover, conjugation methods employed to synthesized trastuzumab-based antibody drug conjugates (ADCs), among which T-DM1 is well known, will be also examined. Finally, although trastuzumab-decorated nanoparticles and liposomes and trastuzumab-based ADCs have proven to have better selectivity and efficacy than loaded drugs, trastuzumab administration is sometimes related to side toxicities and the apparition of resistances. For this reason also, this review focuses at last on the important role that newer antibodies and peptides are acquiring these days in the development of HER2-targeting nanomedicines.

Identification of Prognostic Biomarkers and Molecular Targets Among JAK Family in Breast Cancer

“…3 And according to the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), breast cancer is broadly divided into luminal ER positive (luminal A and luminal B), HER2 enriched, and basal-like molecular subtypes. 4,5 Despite recent great progress in diagnostic methods and treatment technologies, [6][7][8] long-term survival rate of these patients is still not satisfactory, especially in the metastatic setting (median survival less than 24 months). It would be beneficial to conduct more accurate risk assessment and optimize treatment for patients with breast cancer.…”

Nature-Inspired Nanoparticles as Paclitaxel Targeted Carrier for the Treatment of HER2-Positive Breast Cancer

“…Secondly, the carbodiimide coupling strategy was used to covalently bind Tmab to PDA NPs with the aim of verifying whether this type of conjugation improved the antineoplastic activity and selectivity of the resulting NPs (PDA NPs•Tmab@PTX). To do this, in order for the carbodiimide chemistry to be more efficient, the pH of the NP suspensions was acidified [ 26 ], and carboxyl groups of PDA NP surface were activated with EDC and NHS solutions [ 5 ]. Later, in two sequential steps, Tmab and PTX solutions with a similar concentration to those used in the adsorption process were incorporated into NP suspensions.…”

“…However, as the overexpression of this tyrosine kinase (TK) receptor does not occur under normal physiological conditions [ 3 ], on the other hand, it has allowed the development of anti-HER2 targeted agents that have dramatically improved the survival rate of patients suffering from HER2-positive (HER2+) BC [ 2 ]. Undoubtedly, the most widely used HER2-targeted agent to date has been trastuzumab (Herceptin ® , Basilea, Switzarland), a humanized monoclonal antibody (mAb) approved by the major drug regulatory agencies for the past two decades for the treatment of both early and metastatic BC [ 5 ]. Trastuzumab (Tmab) has been shown to induce tumor regression through different molecular mechanisms and to significantly increase overall survival of patients in multiple trials [ 6 , 7 ].…”

Nanomaterials for cancer therapy: current progress and perspectives

“…Trastuzumab (Herceptin) is a mAb used to treat breast cancer with positive expression of human epidermal growth factor receptor 2 (HER2). Research using trastuzumab (Tmab) in ADC system have been conducted, and the result shows improved therapeutic efficacy compared with Tmab alone [ 56 ]. Abedin et al fabricated an antibody–drug nanoparticle, which consists of a core loaded with paclitaxel (PTX) and a surface modified with trastuzumab.…”