Computational pharmaceutics - A new paradigm of drug delivery

In the United States, breast cancer is among the most frequently diagnosed cancers in women. Breast cancer is classified into four major subtypes: human epidermal growth factor receptor 2 (HER2), Luminal-A, Luminal-B, and Basal-like or triple-negative, based on histopathological criteria including the expression of hormone receptors (estrogen receptor and/or progesterone receptor) and/or HER2. Primary breast cancer treatments can include surgery, radiation therapy, systemic chemotherapy, endocrine therapy, and/or targeted therapy. Endocrine therapy has been shown to be effective in hormone receptor-positive breast cancers and is a common choice for adjuvant therapy. However, due to the aggressive nature of triple-negative breast cancer, targeted therapy is becoming a noteworthy area of research in the search for non-endocrine-targets in breast cancer. In addition to HER2-targeted therapy, other emerging therapies include immunotherapy and targeted therapy against critical checkpoints and/or pathways in cell growth. This review summarizes novel targeted breast cancer treatments and explores the possible implications of combination therapy.

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New and Emerging Targeted Therapies for Advanced Breast Cancer

Artificial Intelligence to Bring Nanomedicine to Life.

Immunotherapy has been a milestone in combatting cancer, by complementing or even replacing classic treatments like surgery, chemotherapy, radiation, and anti-hormonal therapy. In 15%-30% of breast cancers, overexpression of the human epidermal growth factor receptor 2 (Her-2/neu) is associated with more aggressive tumor development. Passive immunization/immunotherapy with the recombinantly produced Her-2/neu-targeting monoclonal antibodies (mAbs) pertuzumab and trastuzumab has been shown to effectively treat breast cancer and lead to a significantly better prognosis. However, allergic and hypersensitivity reactions, cardiotoxicity, development of resistance, lack of immunological memory which results in continuous application over a long period, and cost-intensiveness are among the drawbacks associated with this treatment. Furthermore, intrinsic or acquired resistance is associated with the application of therapeutic mAbs, leading to the disease recurrence. Conversely, these drawbacks could be potentially overcome by vaccination, i.e. an active immunization/immunotherapy approach by activating the patient's own immune system to target cancer, along with inducing immunological memory. This review aims to summarize the main approaches investigated and undertaken for the production of Her-2/neu vaccine candidates, with the main focus on peptide-based vaccines and their evaluation in clinical settings. 

http://www.esmoopen.com/article/S2059702921003239/pdf

Vaccination against Her-2/neu, with focus on peptide-based vaccines

In metastatic triple-negative breast cancer (TNBC), the efficacy of immune checkpoint inhibitors (ICIs) in combination with chemotherapy has been demonstrated in randomized clinical trials (RCTs). Despite this, an indirect comparison is not yet available. Reconstruction of individual patient data from Kaplan-Meier curves allows the indirect comparison of different treatments. We analyzed six overall survival (OS) curves from three RCTs. In patients with ≥1% positivity, atezolizumab was found to determine a significantly better OS than pembrolizumab. As regards pembrolizumab, adopting a threshold of PD-L1 positivity ≥10% (as opposed to ≥1%) improved median survival to a remarkable extent (23.0 vs 15.5 months).

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The Degree of Programmed Death-Ligand 1 (PD-L1) Positivity as a Determinant of Outcomes in Metastatic Triple-Negative Breast Cancer Treated With First-Line Immune Checkpoint Inhibitors

Immunotherapy is a major emerging treatment for breast cancer (BC). However, not all breast cancer patients derive benefit from immunotherapy. Predictive biomarkers of immunotherapy, such as tumor mutation burden and tumor-infiltrating lymphocytes, are promising to stratify the patients with BC and optimize the therapeutic effect. Various targets of the immune response pathway have also been explored to expand the modalities of immunotherapy. The use of nanotechnology for the imaging of predictive biomarkers and the combination with other therapeutic modalities presents a number of advantages for the immunotherapy of BC. In this review, we summary the emerging therapeutic modalities of immunotherapy, present prominent examples of immunotherapy in BC, and discuss the future opportunity of nanotechnology in the immunotherapy of BC.

/pdf/recent-progress-on-immunotherapy-for-breast-cancer-tumor-54r767ajyo.pdf

Wenfang Miao

Papers

Recent Progress on Immunotherapy for Breast Cancer: Tumor Microenvironment, Nanotechnology and More.

GANDA: A deep generative adversarial network conditionally generates intratumoral nanoparticles distribution pixels-to-pixels.

Hybridized double-shell periodic mesoporous organosilica nanotheranostics for ultrasound imaging guided photothermal therapy.