Targeted Aptamers Revolutionizing TNBC Treatment

TNBC Breakthrough: How Aptamers Are Revolutionizing Imaging and Therapy

Soraya Malik in Health & Wellness August 2025 • 4 min read.

"Unlocking New Modalities in Triple-Negative Breast Cancer Treatment"

Triple-negative breast cancer (TNBC), representing 15% to 20% of all breast cancer cases, presents a formidable challenge in oncology. Unlike other breast cancers, TNBC lacks the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), which limits the effectiveness of traditional targeted therapies. This absence of specific molecular targets makes TNBC particularly aggressive and difficult to treat, often affecting younger patients and exhibiting a higher propensity for recurrence.

The landscape of TNBC treatment is primarily confined to conventional cytotoxic chemotherapy, which, while effective in some cases, is associated with significant toxicity and the eventual development of resistance. The pressing need for more precise and less harmful treatments has spurred researchers to explore innovative approaches, with a focus on identifying new biomarkers that can improve early detection and enable personalized treatment strategies. One such promising avenue is the use of oligonucleotide aptamers, which have the potential to overcome the limitations of current imaging and therapy modalities.

Aptamers, short single-stranded DNA or RNA molecules, are engineered to bind to specific target molecules with high affinity and specificity, much like antibodies. However, aptamers offer several advantages over antibodies, including their smaller size, ease of synthesis, and ability to be modified for various applications. These unique properties make aptamers ideal candidates for targeted imaging and drug delivery in TNBC, where the heterogeneity of the disease necessitates precise and adaptable therapeutic strategies.

Aptamers: The Key to Precision in TNBC Treatment

Targeted Aptamers Revolutionizing TNBC Treatment

The Systematic Evolution of Ligands by EXponential enrichment (SELEX) technique has emerged as a powerful tool for identifying aptamers that can selectively bind to biomarkers on TNBC cells. This process involves iterative cycles of incubating a library of oligonucleotides with the target cells, partitioning the bound sequences, and amplifying them. Through repeated rounds of selection, aptamers with high affinity and specificity for the target are identified, offering a unique approach to targetable biomarkers.

Cell-SELEX, a variation of the SELEX technique, uses whole cells as the target for aptamer selection, ensuring that the resulting aptamers recognize the target protein in its native conformation on the cell surface. This is particularly important for transmembrane proteins and receptors, which may undergo conformational changes or interact with neighboring proteins. By using entire cells, cell-SELEX eliminates the risk of selecting aptamers that fail to recognize the target in its natural environment, increasing the likelihood of identifying clinically relevant biomarkers.

Aptamers can distinguish between subtle differences in cell surface protein signatures.
Aptamers are effective for cell-type targeting and discrimination.
Cell-SELEX allows selection for cell-internalizing aptamers.
Aptamers enable targeted delivery of therapeutic agents in cancer cell lines.

Aptamers targeting proteins overexpressed in TNBC cells, such as EGFR, PDGFRβ, mucin (MUC1), and nucleolin (NCL), have shown promise in preclinical imaging and therapy. These proteins play critical roles in TNBC behaviors, including vasculogenic mimicry, metastasis, and resistance to therapy. By selectively binding to these targets, aptamers can disrupt their function, deliver therapeutic payloads, or enable targeted imaging of TNBC tumors.

The Future of Aptamers in TNBC Therapy

As we move into an era of precision medicine, aptamers hold tremendous potential as a therapeutic strategy in TNBC. While the application of aptamers as anticancer drugs is still limited, ongoing research efforts are focused on generating aptamers that specifically target disease-related proteins and developing them as targeted imaging agents, therapeutics, and delivery systems. The future of TNBC management may very well depend on the rational design of aptamer-based strategies, offering hope for more effective and personalized treatments.

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This article is based on research published under:

DOI-LINK: 10.3390/ph11040123, Alternate LINK

Title: Tnbc Challenge: Oligonucleotide Aptamers For New Imaging And Therapy Modalities

Subject: Drug Discovery

Journal: Pharmaceuticals

Publisher: MDPI AG

Authors: Simona Camorani, Monica Fedele, Antonella Zannetti, Laura Cerchia

Published: 2018-11-13

Everything You Need To Know

What are aptamers, and what advantages do they offer over traditional antibodies in the context of triple-negative breast cancer (TNBC) treatment?

Aptamers are short, single-stranded DNA or RNA molecules engineered to bind specific target molecules with high affinity and specificity, similar to antibodies. However, aptamers offer advantages such as smaller size, ease of synthesis, and modifiability, making them ideal for targeted imaging and drug delivery. This is particularly useful in triple-negative breast cancer (TNBC) because of the disease's heterogeneity necessitates precise and adaptable therapeutic strategies.

Could you elaborate on the Systematic Evolution of Ligands by EXponential enrichment (SELEX) technique and its role in identifying aptamers for triple-negative breast cancer (TNBC) biomarkers?

The Systematic Evolution of Ligands by EXponential enrichment (SELEX) is a technique used to identify aptamers that selectively bind to biomarkers on TNBC cells. It involves iterative cycles of incubating a library of oligonucleotides with the target cells, separating the bound sequences, and amplifying them. This process identifies aptamers with high affinity and specificity for the target, providing a way to target biomarkers.

What is Cell-SELEX, and how does it improve the selection of aptamers for targeting proteins on triple-negative breast cancer (TNBC) cells?

Cell-SELEX is a variation of the SELEX technique that uses whole cells as the target for aptamer selection. This ensures that the resulting aptamers recognize the target protein in its native conformation on the cell surface. This is crucial for transmembrane proteins and receptors, where conformational changes or interactions with neighboring proteins can affect binding. By using entire cells, cell-SELEX reduces the risk of selecting aptamers that fail to recognize the target in its natural environment.

What are some specific proteins targeted by aptamers in triple-negative breast cancer (TNBC) cells, and how do these interactions contribute to potential therapeutic strategies?

Aptamers targeting proteins overexpressed in TNBC cells, such as EGFR, PDGFRβ, mucin (MUC1), and nucleolin (NCL), have demonstrated potential in preclinical imaging and therapy. These proteins are significant in TNBC behaviors, including vasculogenic mimicry, metastasis, and resistance to therapy. By selectively binding to these targets, aptamers can disrupt their function, deliver therapeutic payloads, or enable targeted imaging of TNBC tumors.

How might aptamer-based strategies influence the future management of triple-negative breast cancer (TNBC), and what ongoing research efforts are focused on advancing this approach?

The future of TNBC management could depend on the rational design of aptamer-based strategies, which may provide more effective and personalized treatments. While the use of aptamers as anticancer drugs is still limited, ongoing research is focused on generating aptamers that specifically target disease-related proteins and developing them as targeted imaging agents, therapeutics, and delivery systems. This approach holds promise for addressing the limitations of current treatments and improving outcomes for patients with triple-negative breast cancer.