Aptamers and Triple Negative Breast Cancer: applications and perspectives in therapy

Breast cancer is the second major cause of cancer related mortality in female patient with 2.3 million women diagnosed worldwide in 2022. Triple negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer, characterized by poor prognosis and high metastatic risk. This subtype lacks expression of targetable biomarkers, and its treatment generally relies on systemic chemotherapy. Traditional chemotherapy is known to bring systemic toxic side effects and could develop multi-drug resistant (MDR) cancers. Recent advances in immunotherapy-based therapeutic options may represent valid alternatives do their effective activation of the patient immune system against the malignant cells. One example of promising immunotherapy is mediated by immune-checkpoint inhibitors (ICI) that shows positive results in TNBC treatment. However new strategies for cancer immunotherapy are needed since most solid tumors do not respond to current approaches. Aptamers are short single-stranded oligonucleotides that can bind to specific target with high affinity and specificity. Aptamers can be used to enhance immunotherapy efficacy by directly targeting tumor cells or immune checkpoints. In this thesis work, three different applications of aptamers in immunotherapy will be analyzed, particularly how they can enhance siRNAs activity, allow better specific NK cells tumor killing ability and act as ICIs to improve chemotherapy efficacy. All the studies pointed out how aptamers are effective enhancer of immunotherapy and may thus be regarded aas powerful tools for breast cancer therapy.