Tumors are not merely masses of neoplastic cells but complex tissues composed of cellular and noncellular elements. This review provides recent data on the main components of a dynamic system, such as carcinoma associated fibroblasts that change the extracellular matrix (ECM) topology, induce stemness and promote metastasis-initiating cells. Altered production and characteristics of collagen, hyaluronan and other ECM proteins induce increased matrix stiffness. Stiffness along with tumor growth-induced solid stress and increased interstitial fluid pressure contribute to tumor progression and therapy resistance. Second, the role of immune cells, cytokines and chemokines is outlined. We discuss other noncellular characteristics of the tumor microenvironment such as hypoxia and extracellular pH in relation to neoangiogenesis. Overall, full understanding of the events driving the interactions between tumor cells and their environment is of crucial importance in overcoming treatment resistance and improving patient outcome.
CTHRC1 and periostin play important roles in breast cancer progression. These preliminary results show that combined evaluation of CTHRC1 and periostin could serve as a potential marker for breast cancer bone metastasis; the other observations contribute to the description of the tumour microenvironment, with implications for lymph node and bone metastasis.
HER1 belonging to the HER family of receptors plays an important role in cell proliferation, migration and protection against apoptosis. HER1 protein could be targeted by monoclonal antibodies and/or tyrosine kinase inhibitors (TKIs). Given signal pathway complexity and HER family member cooperation, it may be better to simultaneously target a number of these receptors (e.g. HER1/HER2 by lapatinib). Thus, HER1 assessment could reveal a particular breast cancer patient group with probably good response to HER1 targeted therapy. TOP2A gene, encoding topoisomerase II alpha (target for anthracyclines) is predictive of response to anthracycline therapy. TOP2A aberrations (amplification, deletion) are found in up to approximately 30-90 % of HER2 amplified breast cancer and amplifications are more common than deletions. Recent publications describe TOP2A amplification also in 2.7-8.8 % HER2 nonamplified breast cancers. Patients with a pathologic complete response to anthracycline based neoadjuvant chemotherapy had a good overall prognosis regardless of molecular subtype of breast cancer. These results suggest that particularly tumors with a complete pathological response to anthracyclines could have TOP2A amplification. C-MYC encodes nuclear DNA binding proteins that regulate proliferation and apoptosis; amplification is associated with poor prognosis and hormonally negative breast carcinoma.
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