Laboratory of Drug Targets Histopathology, Institute of Cardiology, Lithuanian University of Health Sciences, Sukilėlių Av. 13, LT-50161, Kaunas, Lithuania.
Laboratory of Drug Targets Histopathology, Institute of Cardiology, Lithuanian University of Health Sciences, Sukilėlių Av. 13, LT-50161, Kaunas, Lithuania; Life Sciences Center, Vilnius University, Saulėtekio Av. 7, LT-10257, Vilnius, Lithuania.
Life Sci. 2019 Dec 15;239:117009. doi: 10.1016/j.lfs.2019.117009. Epub 2019 Oct 24.
Breast cancer is the most common cancer and the second leading cause of cancer-related death in women worldwide. Despite the early detection of breast cancer and increasing knowledge of its biology and chemo-resistance, metastatic breast cancer is largely incurable disease. We provide a review of the intertumor and intratumor heterogeneity, explain the differences between triple-negative breast cancer subtypes. Also, we describe the interaction of breast tumor cells with their microenvironment cells and explain how this interaction contributes to the tumor progression, metastasis formation and resistance to the treatment.
One of the main causes that complicate the treatment is tumor heterogeneity. It is observed among patients (intertumor heterogeneity) and in each individual tumor (intratumor heterogeneity). In the case of intratumor heterogeneity, the tumor consists of different phenotypical cell populations. During breast cancer subtype identification, a small piece of solid tumor tissue does not necessarily represent all the tumor composition. Breast tumor cell phenotypical differences may appear due to cell localization in different tumor sites, unique response to the treatment, cell interaction with tumor microenvironment or tumor cell interaction with each other. This heterogeneity may lead to breast cancer aggressiveness and challenging treatment.
Understanding the molecular and cellular mechanisms of tumor heterogeneity that are relevant to the development of treatment resistance is a major area of research. Identification of differences between populations and their response to anticancer drugs would help to predict the potential resistance to chemotherapy and thus would help to select the most suitable anticancer treatment.
乳腺癌是全球最常见的癌症，也是女性癌症相关死亡的第二大主要原因。尽管乳腺癌的早期检测以及对其生物学和化疗耐药性的认识不断提高，但转移性乳腺癌在很大程度上仍是无法治愈的疾病。我们提供了对肿瘤间和肿瘤内异质性的综述，解释了三阴性乳腺癌亚型之间的差异。此外，我们描述了乳腺肿瘤细胞与其微环境细胞的相互作用，并解释了这种相互作用如何促进肿瘤进展、转移形成和对治疗的耐药性。
肿瘤异质性是使治疗复杂化的主要原因之一。它存在于患者之间（肿瘤间异质性）和每个肿瘤内部（肿瘤内异质性）。在肿瘤内异质性的情况下，肿瘤由不同表型的细胞群体组成。在乳腺癌亚型鉴定中，一小块实体瘤组织不一定代表所有肿瘤组成。由于细胞在不同肿瘤部位的定位、对治疗的独特反应、细胞与肿瘤微环境的相互作用或肿瘤细胞之间的相互作用，乳腺肿瘤细胞的表型差异可能会出现。这种异质性可能导致乳腺癌的侵袭性和治疗挑战。
了解与治疗耐药性发展相关的肿瘤异质性的分子和细胞机制是一个主要的研究领域。鉴定群体之间的差异及其对抗癌药物的反应将有助于预测潜在的化疗耐药性，从而有助于选择最合适的抗癌治疗。
