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Can nanotechnology be used to treat HER2-positive breast cancer?

Breast cancer is one of the most heterogeneous types of cancer and the primary cause of death for women worldwide. The growth-promoting protein human epidermal growth factor receptor (HER2) is overexpressed in 20-30% of cases of breast cancers which is termed HER2-positive breast cancer, characterized by high levels of aggression, high degree of brain metastases, and poor prognosis. Though it can be therapeutically targeted, HER2-positive breast cancer typically advances and metastasizes more quickly than other types of tumor [1].


Current approach to treat HER2-positive breast cancer


Breast cancer

Along with surgery to remove the tumor, adjuvant therapy, which consists of chemotherapy, radiation therapy, and targeted therapy is used to eliminate any leftover tumor cells and lower the chance of recurrence. Anti-HER2-positive inhibitors have been used successfully to treat patients with HER2-positive breast cancer. After receiving HER2-targeted therapy, the clinical features of the disease have altered. Several types of tyrosine kinase inhibitors have been developed to treat HER2-positive breast cancer, which include:

  • Afatinib

  • Lapatinib

  • Neratinib

  • Tucatinib

  • Pyrotinib

Moreover, the anti-HER2 monoclonal antibody pertuzumab and the antibody-drug conjugates adotrastuzumab, emtansine, famtrastuzumab, and deruxtecan are utilized in both early-stage and metastatic conditions, either alone or in combination with chemotherapy and other HER2-targeting therapies [1,2].


Problem with existing immunotherapies


Tyrosine kinase inhibitors are used to treat HER2-positive breast cancer patients, however, numerous uncertainties remain regarding the effectiveness and safety of the drug combinations, as well as the adverse effects and toxicities. How to choose a tyrosine kinase inhibitor for anti-HER2 therapy based on prior treatment is another unanswered question. HER2-positive metastatic breast cancer is still difficult to treat, despite major advances in systemic medications.


The emergence of drug resistance for anti-HER2 therapies is a major challenge in patients with HER2-positive breast cancer. Only by addressing these unresolved issues, the optimal quality of life in these patients would be achieved. Thus, the nanotechnology approach can be employed in patients with HER2-positive breast cancer to overcome drug resistance and low efficacy in current treatment choices [1–3].


Nanotechnology approach to address HER2-positive breast cancer


Currently, several Nano-based safe and targeted therapeutic agents are being developed to resolve the shortcomings of HER2-positive breast cancer therapy. The potential advantages of nanotechnology include;

  • Early detection

  • Targeted drug delivery to decrease disease burden

  • Elimination of cancer cells and tumors.

Nano formulations are supplied by a mechanism that targets particular markers and can be utilized to lower drug dose concentrations. In patients with HER2-positive breast cancer, it can also be employed as a powerful target for anticancer agents with nanomedicine. Delivery methods for Nano formulation-based targeted therapy include intracellular, epithelial barrier, tumor microenvironment, and distribution to specific immune cells [1–3].


In addition to radiation therapy, photothermal therapy, and photodynamic therapy, which can lower the tumor burden, a therapeutic method based on Nano-formation is more efficient. Drugs based on nanomaterials are efficiently delivered to the target site and allow efficient management of malignant tumors. The HER2-positive breast cancer therapy has been modified by nanoparticle-based Phyto molecules, greatly increasing clinical outcomes. All of these methods have produced notable results and decreased the tumor microenvironment burden [1,3].


Parting words and future directions


For the treatment of breast cancer, several Nano formulations are currently being developed. Nonetheless, due to the increased complexity of nano formulations, caution should be taken before adopting these cutting-edge technologies. The majority of nanotherapeutic strategies for the treatment of breast cancer are focused on active targeting. The incorporation of targeting moieties with nanocarriers increases formulation complexity, which may result in higher toxicity and immunogenicity as well as higher manufacturing costs and problems with good manufacturing practices. It is envisioned that specialists in pharmacokinetics, toxicology, immunology, and oncology will work closely together in the future to produce breast cancer nanomedicine with less side effects and the greatest efficacy.


References


1. Sitia, L. et al. 'HER-2-Targeted Nanoparticles for Breast Cancer Diagnosis and Treatment'. Cancers (Basel). (2022) 14(10), 2424. DOI: 10.3390/cancers14102424.

2. Singh, D.D. et al. 'Clinical updates on tyrosine kinase inhibitors in HER2-positive breast cancer'. Frontiers in Pharmacology. (2022) 13.

3. White, B.E. et al. 'Nanotechnology approaches to addressing HER2-positive breast cancer'. Cancer Nanotechnology. (2020) 11(1), 12. DOI: 10.1186/s12645-020-00068-2.

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