The field of transition-metal based chemotherapeutics are dominated by derivatives of cisplatin, but a major downside of these platinum based chemotherapeutics is their lack of selectivity... Show moreThe field of transition-metal based chemotherapeutics are dominated by derivatives of cisplatin, but a major downside of these platinum based chemotherapeutics is their lack of selectivity that leads to undesirable side effects. In this work we present alternative strategies such as light-activation with different transition-metals such as ruthenium and palladium that have the potential to be more selective than cisplatin type of drugs. Show less
Arens, R.; Hall, T. van; Burg, S.H. van der; Ossendorp, F.; Melief, C.J.M. 2013
One of the most effective anticancer therapy still remains chemotherapy, however, both used as single agent as in combinational regimens, chemotherapy still encounters the problem of therapeutic... Show moreOne of the most effective anticancer therapy still remains chemotherapy, however, both used as single agent as in combinational regimens, chemotherapy still encounters the problem of therapeutic resistance. Limitations of chemotherapy have led to the exploration of alternative anti-cancer approaches in order to improve efficacy, such as chemoprevention. Chemopreventive agents interfere with rate limiting steps in tumor progression, such as for example the establishment of a functional tumor vasculature. Currently, there is a large and unfolding picture of rate-limiting steps during tumor progression which can provide us with numerous potential therapeutic targets, where it is becoming increasingly clear both the tumor itself as its microenvironment contribute in these steps. Current research focuses on exploring chemopreventive approaches as part of combination strategies. One of the most investigated approaches in these combinational strategies is targeting the tumor with chemotherapy together with chemopreventive agents. This thesis explores the use of chemopreventive approaches as monotherapy and in combinational approaches with chemotherapy and explores and discusses their effects on both the tumor as the tumor__s microenvironment. It shows that these combinational approaches hold great promise, if taking both the tumor as the tumor__s microenvironment into account as therapeutic targets. Show less
Survival rates after surgical treatment of gastric, colon and rectal cancer can improve with preoperative and/or postoperative adjuvant treatment with chemo- and/or radiotherapy. The role of... Show moreSurvival rates after surgical treatment of gastric, colon and rectal cancer can improve with preoperative and/or postoperative adjuvant treatment with chemo- and/or radiotherapy. The role of epigenetic aberrancies such as DNA methylation is established to play a pivotal role in gastrointestinal carcinogenesis and malignant progression. This thesis describes novel epigenetic biomarkers that could tailor (neo)adjuvant treatment regimens to the patients who would benefit from them. The same markers could further be used to exclude those patients who would not gain more survival-years and would be unnecessarily exposed to the morbidity/mortality of additional chemo- and/or radiation therapy. Currently, nodal status is the single most important prognostic indicator in gastrointestinal cancers however this can only be reliably assessed by the pathologist after surgery. Currently, neoadjuvant regimens are more and more being studied and shown to be of benefit. This development necessitates biomarkers that are available before the operation. An important derived conclusion from this thesis is that the preoperative availability of primary tumor DNA methylation biomarkers holds great potential for tailoring neoadjuvant therapy. The thesis also describes technical advancements that will enable primary tumor DNA methylation assessment in small amounts of tissue as preoperative diagnostic tumor biopsies harvested during gastroscopy or colonoscopy Show less
