Here is a good review on the state of the art in cancer-research with focus on NSAID's, some mentions of mitochondrial antioxidants and their role in cancer and metastasis.
Drugs targeting mitochondria in metastatic cells to promote selective killing responses and prevent cancer progression are particularly significant in the fight to eliminate metastatic foci that escape surgery or are resistant to radiation or chemotherapy. We expect that additional advances will soon be made to further define mitochondrial alterations in order to inhibit cancer metastases and recurrence. In particular, the identification of selective triggers targeting critical thiols that activate the mPTP in metastasizing cells should make this goal achievable.
Although the NSAIDs can be toxic to normal cells such as liver and kidney, they show much greater selectivity and at lower concentrations target the highly metastatic cancer cells emerging from hypoxia and hypoglycemic stress with their heightened pro-oxidative states, as discussed throughout this review. The preclinical and clinical data provide sufficient evidence for their selectivity and specificity for inducing metastatic cancer cell death and should now pave the way for future therapeutic clinical trials to be undertaken with advanced stage human cancer patients using improved NSAIDs combined with other chemotherapeutic agents.
No doubt further research will continue to refine the basic mechanisms for hypoxic/oxidative changes in tumor cell mitochondria and provide novel targets to fight against cancer by understanding the specific nature of changes in their activity, some of which have been highlighted in this review. Despite improved understanding of cancer and some advances in treatments, high rates of metastases and tumor recurrence remain a worldwide problem and a considerable health burden on society. In Australia, the annual incidence of new cases of cancer is continually rising (now near 130,000 with a predicted increase to 150,000 by 2020; AIHW 2012) and cancer is a leading cause of death (49,000 in 2008 for Australia and New Zealand) with a huge social and economic impact (currently estimated in Australia as a $2 billion health cost). In Mexico and Central American Countries, 176,000 new cancer cases and 108,000 deaths were registered in 2008 [286], with breast cancer having the highest incidence in females [287]. Consequently, further research is needed to fully understand the effects of hypoxia and ROS activated changes during primary tumor progression that promote metastasis. The goal is to identify specific new and selective targets for anticancer therapy that will inhibit primary cancer, metastatic development and cancer recurrence.
http://www.mdpi.com/...8247/8/1/62/htm
Edited by Cosmicalstorm, 28 February 2015 - 09:55 AM.
