Molecular markers associated with the outcome of tamoxifen treatment in estrogen receptor-positive breast cancer patients: scoping review and in silico analysis

Abstract

Tamoxifen (TMX) is used as adjuvant therapy for estrogen receptor-positive (ER+) breast cancer cases due to its affinity and inhibitory effects. However, about 30% of cases show drug resistance, resulting in recurrence and metastasis, the leading causes of death. A literature review can help to elucidate the main cellular processes involved in TMX resistance. A scoping review was performed to find clinical studies investigating the association of expression of molecular markers profiles with long-term outcomes in ER+ patients treated with TMX. In silico analysis was performed to assess the interrelationship among the selected markers, evaluating the joint involvement with the biological processes. Forty-five studies were selected according to the inclusion and exclusion criteria. After clustering and gene ontology analysis, 23 molecular markers were significantly associated, forming three clusters of strong correlation with cell cycle regulation, signal transduction of proliferative stimuli, and hormone response involved in morphogenesis and differentiation of mammary gland. Also, it was found that overexpression of markers in selected clusters is a significant indicator of poor overall survival. The proposed review offered a better understanding of independent data from the literature, revealing an integrative network of markers involved in cellular processes that could modulate the response of TMX. Analysis of these mechanisms and their molecular components could improve the effectiveness of TMX.

Magnetic hybrid nanomaterial based on a natural polymer and an amino acid as pH/temperature dual-responsive nanoplatform for the delivery of tamoxifen

“…Thus, at acidic pH, COO − of HA were protonated, displacing the drug and, therefore, triggering its release (equation shown in Figure 6C). Since TMX is mainly used to treat a specific type of breast cancer known as estrogen receptor-positive (Osborne et al, 2000;Dal Berto et al, 2021), it was decided to challenge the HMNP-TMX, and its biological performance was studied against MDA-MB-231 triple negative human breast cancer cells, a subtype clinically more aggressive than other breast cancer subtypes (Mahmoud et al, 2022). These cells lack estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2.…”

p53 regulates expression of nuclear envelope components in cancer cells

“…Furthermore, p53 depletion or mutation might predispose the cell to undergo genomic instability and hence contributing to the cancer evolution [22,36,42,51]. Future work will be required for a comprehensive dissection of p53-nucleus interplay to better define a druggable approach model in the context of human disease and cancer pathogenesis [1], Dal [11]. This will be extremely helpful for the identification of novel potential therapeutic targets and prognostic factors.…”