Breast cancer future or investigational therapies

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2]

Immunotherapeutic interventions

Generally, cancer immunotherapy refers to immune checkpoint inhibitors and cytokines, adoptive cell therapy, and cancer vaccines.

Immune checkpoint inhibitors

Programmed cell death protein 1 (PD-1)

• Programmed cell death protein 1 (PD-1) is an inhibitory immune checkpoint inhibitor that limits T-cell effector function within tissues, and it is expressed on the surfaces of immune effector cells (T-cells, B cells, NK cells, DCs, and many TILs)and has two known ligands, namely, PD-L1 and PD-L2.

• Anti-PD-1 antibodies (Pembrolizumab, JS001, PDR001, and Nivolumab)
• Anti-PD-L1 antibodies (Atezolizumab and Durvalumab)

Anti-CTLA-4 antibodies (Ipilimumab and Tremelimumab)

• Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is a T-cell inhibitory receptor that is expressed on activated CD8+ T cells and CD4+ regulatory T cells that express CD25 and Foxp3.

• Immune checkpoint inhibitors might be combined with targeted therapy (i.e Vascular endothelial growth factor (VEGF) and EGFR (epidermal growth factor receptor) inhibitors)

Adoptive cell therapy

• Adoptive cell therapy is defined as the induction of anti-tumor immune responses via the isolation of highly active and tumor-specific lymphocytes, such as TILs, cytotoxic T lymphocytes (CTLs), Th cells, NK and DC cells.

• Chimeric antigen receptors T-cell-based therapy
• T cell receptors (TCRs)—engineered T cells

Cancer vaccines

• Cancer-testis antigens (CTA) as a vaccine target
• Personalized peptide vaccination (PPV)
• Antigen-presenting cell (APC) and DC-based tumor vaccination

Antibody–drug conjugates (ADC)

• Utilization of monoclonal antibodies that recognize TAAs/TSAs and preferably internalizes when bound to the tumour cells to deliver highly potent cytotoxic agents.

Exosomes

• Exosomes are mall 30–100 nm sized extracellular vesicles
• They are are present in many eukaryotic fluids (normal and malignant)
• Particles that encapsulate contents, such as microRNAs.
• Exosome messaging contributes to:

• TME interactions, including:

• Immune suppression and immune escape,
• Invasive growth, adhesion, angiogenesis,
• Radiation resistance, chemo-resistance
• Genetic intercellular exchange,
• May manipulate tumor progression and metastatic cascade

Endoxifen

• Endoxifen is a nonsteroidal selective estrogen receptor modulator (SERM) of the triphenylethylene group. It is an active metabolite of tamoxifen and has been found to be effective in patients that have failed previous hormonal therapies (tamoxifen, aromatase inhibitors, and fulvestrant).