Breast cancer as an example of tumour heterogeneity and tumour cell plasticity during malignant progression

Abstract

Heterogeneity within a tumour increases its ability to adapt to constantly changing constraints, but adversely affects a patient’s prognosis, therapy response and clinical outcome. Intratumoural heterogeneity results from a combination of extrinsic factors from the tumour microenvironment and intrinsic parameters from the cancer cells themselves, including their genetic, epigenetic and transcriptomic traits, their ability to proliferate, migrate and invade, and their stemness and plasticity attributes. Cell plasticity constitutes the ability of cancer cells to rapidly reprogramme their gene expression repertoire, to change their behaviour and identities, and to adapt to microenvironmental cues. These features also directly contribute to tumour heterogeneity and are critical for malignant tumour progression. In this article, we use breast cancer as an example of the origins of tumour heterogeneity (in particular, the mutational spectrum and clonal evolution of progressing tumours) and of tumour cell plasticity (in particular, that shown by tumour cells undergoing epithelial-to-mesenchymal transition), as well as considering interclonal cooperativity and cell plasticity as sources of cancer cell heterogeneity. We review current knowledge on the functional contribution of cell plasticity and tumour heterogeneity to malignant tumour progression, metastasis formation and therapy resistance.

Lysophosphatidic acid receptor 6 regulated by miR-27a-3p attenuates tumor proliferation in breast cancer

“…However, resistance to endocrine therapy and chemotherapy in patients with breast cancer typically leads to regional recurrence and distal metastasis, which causes high mortality [1,2]. Notably, breast cancer exhibits high heterogeneity [2,3], particularly, intratumoral heterogeneity, which is generated from both extrinsic factors from the tumor microenvironment and intrinsic parameters from the cancer cells [4]. The intrinsic parameters primarily include genetic, epigenetic, and transcriptomic traits, which affect gene expression and activation of related pathways.…”

Biological and Mechanical Characterization of the Random Positioning Machine (RPM) for Microgravity Simulations

“…Cancer still remains the second leading cause of death worldwide after cardiovascular diseases; thus, several studies have investigated the influence of microgravity on cancer cell growth, proliferation, stemness, and metastasis [30]. One of the most common cancers in women worldwide is represented by breast tumors, which are highly heterogeneous at the histopathological, molecular, and clinical level [31], and among these, the TNBC forms are one of the most aggressive and with a poor prognosis [20].…”

Performance Comparisons of AlexNet and GoogLeNet in Cell Growth Inhibition IC50 Prediction

“…In particular, the micro-average AUROCs of LASSO and DeepIC50 were closer to 0.5, in comparison to GoogLeNet (Figure S1B), indicating that LASSO and DeepIC50 made random guesses. The breast cancer (BRCA) is considered as one of the most heterogenous tumor [51], indicating that the cancer differs greatly among the cancer patients [52]. Even patients belonging to the same molecular subtype in BRCA present different clinical outcomes.…”