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Antibody Conjugation of Nanoparticles as Therapeutics for Breast Cancer Treatment.

ABSTRACT: Breast cancer is the most common invasive tumor in women and the second leading cause of cancer-related death. Nanomedicine raises high expectations for millions of patients as it can provide better, more efficient, and affordable healthcare, and it has the potential to develop novel therapeutics for the treatment of solid tumors. In this regard, targeted therapies can be encapsulated into nanocarriers, and these nanovehicles are guided to the tumors through conjugation with antibodies-the so-called antibody-conjugated nanoparticles (ACNPs). ACNPs can preserve the chemical structure of drugs, deliver them in a controlled manner, and reduce toxicity. As certain breast cancer subtypes and indications have limited therapeutic options, this field provides hope for the future treatment of patients with difficult to treat breast cancers. In this review, we discuss the application of ACNPs for the treatment of this disease. Given the fact that ACNPs have shown clinical activity in this clinical setting, special emphasis on the role of the nanovehicles and their translation to the clinic is placed on the revision.

SUBMITTER: Juan A

PROVIDER: S-EPMC7504566 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Antibody Conjugation of Nanoparticles as Therapeutics for Breast Cancer Treatment.

Juan Alberto A Cimas Francisco J FJ Bravo Iván I Pandiella Atanasio A Ocaña Alberto A Alonso-Moreno Carlos C

International journal of molecular sciences 20200821 17

Breast cancer is the most common invasive tumor in women and the second leading cause of cancer-related death. Nanomedicine raises high expectations for millions of patients as it can provide better, more efficient, and affordable healthcare, and it has the potential to develop novel therapeutics for the treatment of solid tumors. In this regard, targeted therapies can be encapsulated into nanocarriers, and these nanovehicles are guided to the tumors through conjugation with antibodies-the so-ca ...[more]

PMID: 32825618

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Project description:Progress in the treatment of cancer over the past decade has been slow. Targeting a mutated gene of an individual patient tumor, tumor-guided agents, and the first draft of the human genome sequence have created an overenthusiasm to achieve personalized medicine. However, we now know that this effort is misleading. Extreme interpatient and intratumor heterogeneity, scarce knowledge in how genome-wide mutational landscape and epigenetic changes affect transcriptional processes, gene expression, signaling transduction networks and cell regulation, and clinical assessment of temporary efficacy of targeted drugs explain the limitations of these currently available agents. Trastuzumab and a few other monoclonal antibodies or small-molecule tyrosine kinase inhibitors (TKIs) represent an exception to this rule. By blocking ligand-binding receptor in patients with human epidermal growth factor receptor 2 (HER2) amplification and overexpression, trastuzumab added to chemotherapy in HER2-positive patients has been proven to provide significant overall survival benefit in both metastatic and adjuvant settings. Lapatinib, a small-molecule dual inhibitor (TKI) of both HER2 and EGFR (epidermal growth factor receptor) pathways, has an antitumor activity translated into progression-free survival benefit in HER2-positive metastatic patients previously treated with a taxane, an anthracycline, and trastuzumab. Despite these advances, ~25% of patients with HER2-positive breast cancer experience recurrence in the adjuvant setting, while in the metastatic setting, median survival time is 25 months. In this review, we discuss the safety, efficacy, and limitations of the trastuzumab emtansine (T-DM1) conjugate in the treatment of HER2-positive metastatic breast cancer. We also highlight Phase III randomized trials, currently underway, using either the T-DM1 conjugate or various combinations of monoclonal antibodies and TKIs. Moreover, in contrast with all these agents developed on the basis of "central dogma" of simplified reductionist transcription and single gene-phenotype linear relationship, we summarize the emerging, amazing era of next-generation, transcriptional circuitry and intracellular signaling network-based drugs guided by the latest advances in genome science and dynamics of network biology.

Dataset Information

Antibody Conjugation of Nanoparticles as Therapeutics for Breast Cancer Treatment.

Publications

Antibody Conjugation of Nanoparticles as Therapeutics for Breast Cancer Treatment.

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