Tumor MicroEnvironment (TME)
Breast cancer is one of the most common female cancers and known to metastasize to brain. It is acknowledged that brain prevents the entering of substances in the blood stream by blood-brain barrier (BBB) and only tiny materials can across the BBB. In terms of size, tumor cells are too large to penetrate the BBB. However, 30% of all women with metastatic breast cancer develop brain tumors. Recently, many studies have suggested that the reciprocal interaction between cancer cells and environment is important for cancer metastasis. Therefore, it is plausible that tumor microenvironment is involved in breast cancer brain metastasis. Our research is to understand the role of interface zone (IZ) in breast cancer brain metastasis. In particular, we have created a vital in vitro model of BBB transmigration and found that cancer-associated fibroblast produces certain substances that help tumor cells penetrate the BBB.
Another special feature of breast cancer is ‘dormancy’. Dormancy in general means a period in an organism’s life cycle when growth, development, and physical activity are temporarily stopped. In clinic, many breast cancer patients experience tumor recurrences, which happen months, years, or even decades even after successful primary tumor treatment. This implies that despite of systemic adjuvant therapy, some tumor cells survive in distant organs such as bone marrow or lung. The problem is, those recurred tumors are often located not in mammary tissues but distant organs such as bone or lung, and they are resistant to multiple anti-tumor therapeutics, resulting mortality in the end. How those tumor cells disseminated into secondary sites survive during the period is the key question, and the concept of ‘dormancy’ will be the key to answer this question.
Cancer Stem Cell (CSC)
CSCs resemble cells that have undergone epithelial–mesenchymal transition (EMT) with regard to their invasiveness and motility. EMT, which is associated with a key step in tumor metastasis via induction of a highly invasive phenotype, has been intensely studied. And CSCs have been found to transiently acquire stem cell-like properties as a consequence of EMT. CSCs also are inherently chemoresistant and radioresistant. Recently, side population (SP) cells have been shown to express increased levels of MDR1 (multidrugresistance protein 1) and ABCG2 (ATP-binding cassette, sub-family G, member 2) transporters, which can extrude certain chemotherapeutic agents and have been implicated in drug resistance. Importantly, SP cells appear to be enriched in stem cells. Although this issue remains controversial, identifying and characterizing human ovarian CSCs would provide a critical step toward the identification of drugs with therapeutic efficacy against CSCs and the development of novel therapeutic strategies for the long-term control of cancer.
Molecular pathology is an emerging discipline within pathology which is focused in the study and diagnosis of disease through the examination of molecules within organs, tissues or bodily fluids. Molecular pathology shares some aspects of practice with both anatomic pathology and clinical pathology, molecular biology, biochemistry, proteomics and genetics, and is sometimes considered a “crossover” discipline. It is multi-disciplinary in nature and focuses mainly on the sub-microscopic aspects of disease. It is a scientific discipline that encompasses the development of molecular and genetic approaches to the diagnosis and classification of human diseases, the design and validation of predictive biomarkers for treatment response and disease progression, the susceptibility of individuals of different genetic constitution to develop disorders.