Predictive biomarkers for triple negative breast cancer treated with platinum-based chemotherapy

Abstract

Treatment of triple negative breast cancer (TNBC) has been a big challenge since it is defined. To date, platinum-based chemotherapy has played a significant role in the treatment of TNBC patients. However, some patients do not respond to platinum salts or gradually develop chemoresistance, resulting in little effect, or even some adverse effects. Here, we review numerous preclinical and clinical investigations to summarize possible mechanisms and potential predictive biomarkers of platinum in TNBC. The homologous recombination deficiency (HRD) resulting from the loss of BRCA function is the main rationale of platinum efficacy in TNBC. BRCA mutation and methylation have been demonstrated to be important potential biomarkers. Based on genome-wide effects, BRCA-like classifier can identify the functional loss of BRCA and work as the predictor. HRD score that is able to identify the "BRCAness" and predict the sensitivity of platinum is increasingly considered. Taken together, all findings suggest that HR deficiency profile encompassed by BRCA mutation and high HRD score could predict response to platinum, even to other DNA-damage inducing agents. p53 family members and molecular subtypes of TNBC are also important alternative considerations for predicting platinum response based on the preclinical trials. Currently, tumor infiltrating lymphocyte level and thrombocytopenia are emerging as predictive biomarkers.

APE1 and NPM1 protect cancer cells from platinum compounds cytotoxicity and their expression pattern has a prognostic value in TNBC

“…Two different TNBC cell lines (HCC70 and HCC1937) were chosen as a model for this study, based on their different mutational status of the TP53 and BRCA1 genes, two important players in the response to Pt-salts [82,83]. First, basal levels of APE1 and NPM1 proteins were analyzed in both cell lines.…”

Triple-Negative Breast Cancer, Cisplatin and Calpain-1

“…A key feature of platinum based drugs is that once platinum salts enter cells, they can bind to DNA to form Platinum-DNA adducts that can cause damage to the DNA. Following DNA damage, cell cycle checkpoints are activated to repair either the damaged DNA or induce apoptosis (cell death) [13,14]. Thus, the ultimate goal in the application of platinum-based chemotherapy is to shift the dynamics away from Breast Cancer and Surgery cell growth and survival in favor of cell differentiation and apoptosis.…”

“…Although PBDs are initially effective, their efficacy is limited by the occurrence of resistance, which is attributed to alterations in cellular pathways such as DNA repair, drug transport, drug metabolism and apoptosis [16]. Several studies have explored the cellular and molecular pathways involved in the mechanism of PBDs resistance to breast cancer [13,[16][17][18]. However, only a few ultrastructural studies on the intracellular organelles of breast cancer cells have been performed to determine the effectiveness of these drugs.…”

Fangjihuangqi Decoction inhibits MDA‐MB‐231 cell invasion in vitro and decreases tumor growth and metastasis in triple‐negative breast cancer xenografts tumor zebrafish model

“…TNBC is more aggressive, with local recurrence, organ metastasis (lungs, liver, bones, and brain), and poor prognosis . Besides, TNBC patients had worse overall survival (OS) than patients with non‐TNBC characteristics and the median OS of patients with metastatic TNBC is approximately 9‐12 months, which leads to an urgent need for new targeted therapies for TNBC and metastatic …”

“…8,9 Besides, TNBC patients had worse overall survival (OS) than patients with non-TNBC characteristics 10 and the median OS of patients with metastatic TNBC is approximately 9-12 months, which leads to an urgent need for new targeted therapies for TNBC and metastatic. 11 Epithelial-mesenchymal transition (EMT) is the process of epithelial cells to obtain mesenchymal phenotype. Epithelial cells have tight junction, while mesenchymal cells lack cell junctions and therefore are loose, mobile, and invasive, which are intrinsic properties of mesenchymal cells.…”