 |
Henrik Ditzel Professor, Physician-in-Chief Head of Department Department of Cancer and Inflammation Research Phone: 6550 3781 Email: hditzel@health.sdu.dk |
Despite advances in treatments for breast cancer, most patients receive standard therapies even though a large percentage of the patients do not respond to the treatment and develop disease recurrence or progression. The current problem is that we know that the standard treatments benefit breast cancer patients as a group, but we do not know which patients within the group will benefit from a given treatment and which will not. Predictive biomarkers are needed to determine this. This will assure that the patient will receive the optimal treatment from the beginning and spare a large number of patients with resistant tumors from side-effects induced by ineffective therapy, as well as have a major impact on the economic health system by avoiding the cost of ineffective treatments.
Our research efforts focus on five areas connected with breast cancer, the most frequent type of cancer among women. This research encompasses:
• ENDOCRINE RESISTANCE IN ER+ BREAST CANCER
Tamoxifen and aromatase inhibitors are effective in treating hormone-sensitive breast cancers. However, since approximately 1/3 of the patients do not respond to these treatments, we are working to identify which women will benefit from these substances with the help of genetic and protein profiling, and we have developed such profiles for patients who are being treated with tamoxifen, which we are now further testing. We are also developing a genetic profile for aromatase inhibitor resistance to bring a biological insight to the mechanisms of endocrine resistance and identify novel drug target and treatment strategies for breast cancer patients with endocrine resistance. For more information please see some of our recent publications on the topic, click here, 2, 3 and 4.
• EARLY DETECTION OF BREAST CANCER
Currently, mammography is the standard screening tool worldwide, but this technique has several limitations. Therefore, there is a need for highly sensitive and specific blood based assays for early detection of breast cancer, to be used alone or in combination with mammography. We have recently identified and validated a 9-miRNAs signature that provided considerable discrimination between breast cancer patients and healthy controls and we are currently performing a prospectively study evaluating the increased diagnostic value of combining mammography and our miRNA signature blood test. In addition, we will examine whether particular somatic mutations or methylation changes present in the tumors can be used as blood-based markers for early detection and follow-up of early-stage breast cancer.
• TUMOR-INITIATING/CANCER STEM CELLS IN BREAST CANCER
An associated topic to drug resistance is cancer stem cells, a small subpopulation of cancer cells with features distinct from that of the cancer cells that constitute the bulk of the tumour. Cancer stem cells, or more correctly tumour-initiating cells, are believed to initiate and maintain the tumours. They are resistant to standard therapy and, since just a couple of cancer stem cells could mean that cancer will return, we are attempting – at the genetic and protein levels – to discover how cancer stem cells function and, most importantly, how this function can be abolished. Using single cell cloning, we have established a number of cell lines that have either a tumor-initiating or a more differentiated cell phenotype. Currently, we are studying the sensitivity of these cells to various chemotherapeutic agents, their ability to form tumours in mice and mammospheres in vitro, and their gene and protein expression profiles. For more information please see some of our recent publications on the topic, click here.
• UNDERSTANDING AND INHIBITION OF THE METASTATIC PROCESS
Metastases are the primary cause of cancer-related death. Many of the initial steps of the metastatic process cannot be analyzed using patient material or simple in vitro assays. However, an in vivo model based on inoculation of human cell lines into mice may allow such studies, and comparative molecular screening and functional evaluation of candidate metastasis-related genes and proteins may identify key molecules in the metastasis process and therapeutic targets. Currently, we are using next-generation sequencing and proteomic analyses to evaluate molecular alterations associated with the metastasis process. For more information please see some of our recent publications on the topic, click here, 2, 3 and 4.
• ELUCIDATING THE FUNCTION OF CANCER/TESTIS-ASSOCIATED PROTEINS
Cancer/testis-associated proteins (CTAs) are a family of proteins encoded by genes that are normally expressed only in the human germ line, but which also occur in various tumours. The restriction of CTA expression to immunoprivileged normal tissues (testis and, infrequently, ovary) and the high expression frequency in different types of cancer makes them attractive candidates for cancer-specific immunotherapy. Little is known about the function of these proteins in normal and malignant tissues. Our preliminary results suggest that several CTA play a role in germ cell differentiation and may be important in the tumorigenicity process. For more information please see some of our recent publications on the topic, click here and here.
We are working on similar aspects of other types of cancer, such as prognostic and predictive markers in non-small cell lung cancer, with special focus on patients with resistance to EGFRmutant-targeting drugs and CTA expression in melanoma.
Our next-generation sequencing research is performed as part of our involvement in the Sino-Danish Breast Cancer Research Grundforskningscenter of Excellence, and our cellular and animal imaging is performed as part of our involvement in the Danish Molecular Biomedical Imaging Center (DaMBIC).
Henrik Ditzel's research group is supported by NEYE-Fonden through grant to professor Henrik Ditzel,professor Morten Gjerstorff, associated professor Mikkel Green Terp and postdoc Martina Tuttolomondo.