There is a pending need for prognostic and predictive biomarkers in the treatment of patients with colorectal cancer.This thesis describes the prognostic and predictive application of the tumor... Show moreThere is a pending need for prognostic and predictive biomarkers in the treatment of patients with colorectal cancer.This thesis describes the prognostic and predictive application of the tumor-stroma ratio (TSR) in colorectal cancer, focusing on expanding current clinical-pathological standards and combining TSR with other diagnostic parameters. The TSR is a microscopy scoring method performed on hematoxylin-eosin stained tissue slides used for routine pathology assessment, and has proven to be a robust prognostic maker. Here, we investigate whether the TSR also exhibits predictive value with regard to adjuvant targeted therapy in stage II and III colon cancer. Moreover, exploring the value of collagen fiber organization in the intratumoral stroma, as well as combining this parameter with the TSR. Finally, expanding the application of the TSR with radiological diagnostics in rectal cancer. Assessing is there is a correlation between TSR and apparent diffusion coefficient values obtained from diagnostically performed MRI-DWI scans, in order to determine if there is potential with regards to neoadjuvant treatment choices or patient follow-up. Show less
Therapy resistance is a known problem in breast cancer and is associated with a variety of mechanisms. The role of the tumor microenvironment in cancer development and resistance mechanisms is... Show moreTherapy resistance is a known problem in breast cancer and is associated with a variety of mechanisms. The role of the tumor microenvironment in cancer development and resistance mechanisms is becoming increasingly understood. Tumor-stroma is the main component of the tumor microenvironment. Stromal cells like cancer-associated fibroblasts (CAFs) are believed to contribute to chemotherapy resistance via the production of several secreted factors like cytokines and chemokines. CAFs are found to influence disease progression; patients with primary tumors with a high amount of tumor-stroma have a significantly worse outcome. Therefore the role of CAFs resistance mechanisms makes them a promising target in anti-cancer therapy. An overview of recent advances in strategies to target breast cancer stroma is given and the current literature regarding these stromal targets is discussed. CAF-specific proteins as well as secreted molecules involved in tumor-stroma interactions provide possibilities for stroma-specific therapy. The development of stroma-specific therapy is still in its infancy and the available literature is limited. Within the scope of personalized treatment, biomarkers based on the tumor-stroma have future potential for the improvement of treatment via image-guided surgery (IGS) and PET scanning. Show less
