Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) - Volume 8, Issue 4, 2008

A number of human proteins have been characterized which have important roles in pathways responsible for sensing, responding, and repairing DNA damage. Collectively, these proteins are referred to as DNA repair or DNA damage response proteins, but their functions are specific in terms of pathways that can be potentially manipulated to modulate the biological response to a given cytotoxic agent. Selective inactivation of Read More

In both bacteria and eukaryotes the alkylated, oxidized, and deaminated bases and depurinated lesions are primarily repaired via an endogenous preventive pathway, i.e. base excision repair (BER). Radiation therapy and chemotherapy are two important modes of cancer treatment. Many of those therapeutic agents used in the clinic have the ability to induce the DNA damage; however, they may also be highly cytotoxic, causi Read More

The cytotoxicity of many antineoplastic agents is due to their capacity to damage DNA and there is evidence indicating that DNA repair contributes to the cellular resistance to such agents. DNA strand breaks constitute a significant proportion of the lesions generated by a broad range of genotoxic agents, either directly, or during the course of DNA repair. Strand breaks that are caused by many agents including ionizing ra Read More

Tumor resistance to cytotoxic chemotherapy drugs and their toxicity to normal cells are major clinical obstacles to anticancer therapy effectiveness. Alterations in various DNA repair pathways play a key role in the development of both mechanisms of drug resistance and toxicity. Since deregulation of the DNA damage response and alterations in DNA repair pathways are relatively common in human cancer, the k Read More

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a recently discovered enzyme that catalyzes the hydrolysis of 3'-phosphotyrosyl bonds. Such linkages form in vivo following the DNA processing activity of topoisomerase I (Top1). For this reason, Tdp1 has been implicated in the repair of irreversible Top1-DNA covalent complexes, which can be generated by either exogenous or endogenous factors. Tdp1 has been regarded as a pote Read More

It has been proposed that selective inactivation of a DNA repair pathway may enhance anti-cancer therapies that eliminate cancerous cells through the cytotoxic effects of DNA damaging agents or radiation. Given the unique and critically important roles of DNA helicases in the DNA damage response, DNA repair, and maintenance of genomic stability, a number of strategies currently being explored or in use to combat cance Read More

Cancer is a disease of uncontrolled cellular proliferation. Chemotherapy and radiation therapy are the two main modalities for cancer treatment. However, some cancer types have been found to be refractory to these treatments. Additionally, certain chemicals that are used in clinical trials produce high cytotoxicity as a secondary effect. Hence, current research is focused on finding ways by which cancer cells can be specifi Read More

Cancer therapeutics include an ever-increasing array of tools at the disposal of clinicians in their treatment of this disease. However, cancer is a tough opponent in this battle and current treatments which typically include radiotherapy, chemotherapy and surgery are not often enough to rid the patient of his or her cancer. Cancer cells can become resistant to the treatments directed at them and overcoming this drug resista Read More

Promising research on DNA repair signaling pathways predicts a new age of anti-tumor drugs. This research was initiated through the discovery and characterization of proteins that functioned together in signaling pathways to sense, respond, and repair DNA damage. It was realized that tumor cells often lacked distinct DNA repair pathways, but simultaneously relied heavily on compensating pathways. More recently, rese Read More

We have very recently highlighted possible connections between DNA polymerases, the main enzymes in the DNA metabolism, and human diseases (Ramadan, K., Maga, G. and Hubscher, U.: DNA polymerases and diseases, In: Genome Integrity: Facets and Perspectives ed. Lankenau, D.-H. Springer Verlag, Heidelberg Germany, Vol 1, pp. 69-102, 2007). Beside a role in DNA replication of the genome DNA polymerases have f Read More

In the decade since the BRCA1 and BRCA2 genes were cloned, much has been learned about the function of these two major causes of familial breast cancer. BRCA2 has been shown to play a direct role in the repair of DNA by homologous recombination, by interacting with the Rad51 protein and facilitating the formation of Rad51 aggregates at the site of DNA damage. It likely plays a similar role when double strand br Read More