This method is effective in different cancer types and can nullify cancer survival response. Effective against cancer hypoxia. Powerful in terms of reactivity and selectivity.

About

New Cancer Treatment Therapy Many existing anticancer therapies generate reactive oxygen species (ROS) inside cancer cells in order to kill them. For example many chemotherapeutic strategies are designed to exuberantly-increase cellular ROS levels with the goal to induce irreparable damages subsequently resulting in tumor cell apoptosis [1]. Other examples are also combination therapies of gemcitabine with trichostatin A, epigallocate-3-gallate (EGCG), capsaicin and benzyl isothiocyanate (BITC) [2, 3, 4], non-steroidal and anti-inflammatory drug Sulindac [5], etc. All of these drugs and several other compounds share the same mechanism, namely to elevate intracellular ROS levels to trigger apoptosis. However, the limited amount of ROS production inside cancer cells, chemical composition and selective target are the limiting factors for many existing therapies, and therefore, this challenge demands a new mechanism that can nullify cancer survival response. The objective is to use a novel therapeutic strategy that can generate external and internal (inside cells) reactive oxygen species simultaneously, thus, creating a unique and powerful killing synergy against cancer cells. The amount of reactive oxygen species (ROS) produced by proposed treatment method, chemical composition and target, can be tightly controlled, allowing fine tuning of therapeutic effect. This treatment method will provide fine tuning of intracellular ROS signaling to effectively deprive cells from ROS-induced tumor promoting events, towards tipping the balance to ROS-induced apoptotic signaling. The potential of this new treatment therapy to deliver externally generated reactive species as well as activate ROS generation molecules inside cancer cells simultaneously is a unique contribution that was not considered yet in scientific community. Here, I propose for the first time an integrated focus on this novel synergy that could lead to new effective therapy for different cancer types. Based on the existing evidence this is a breakthrough method that creates unique and powerful synergy in terms of reactivity, selectivity, and safety that go well beyond the simple combination of two reactive species. This treatment is well tolerated, essentially painless, and noninvasive. It has no long-term side effects, takes only a short time and can be targeted very precisely. Scientific Rationale Generation of reactive radicals is an effective way of killing a wide range of microorganisms and fighting against cancer based on their strong oxidative effect. However, although many of the existing anticancer therapies aim to increase ROS levels and selectively kill cancer cells, they cannot modulate effectively their concentration and composition and destroy completely cancer cells. Therefore, the capacity of this novel treatment method, to control and therapeutically administer ROS/RNS molecules would overcome the limitations of many ROS based treatment therapies and selectively kill cancer cells. This mechanism creates a powerful killing synergy against cancer cells where both external and internal reactive oxygen species from two sources will synergize inside treated cells. The treatment method is selective, meaning tunable between damage to cancer cells without damage to the normal cells which makes it more attractive and efficient for the treatment. This combination takes advantage of different strengths of each of the two technologies and provides an unprecedented grand opportunity for cancer treatment. In addition, this method can be a good alternative to treat cancer hypoxia which contributes to the malignant phenotype and aggressive tumor progression [12]. In fact, hypoxia is a crucial mediator of chemo and radioresistance and a major reason for treatment failure in cancer patients. Intratumoral hypoxia prevents ROS formation, resulting in inefficient DNA strand breaks and IR resistance [13]. Results have shown that ROS level in the resistant cancer cells is usually lower than that in their parental sensitive cells [14, 15]. The limited reactive oxygen radicals generated during hypoxia by using some of the existing methods may cause other adaptive responses like up-regulation of antioxidants within tumor cells that confer resistance to apoptosis. All of this up-regulation of anti-ROS defenses may eliminate ROS induced cytotoxicity and apoptosis to increase the detoxification ability (resistance) of tumor cells to such treatment therapies. Fortunately, this new proposal can meet such requirements. Further increase of ROS stress in cancer cells using external ROS provided with this treatment strategy will cause elevation of ROS above the threshold level, leading to cell death. This treatment strategy will provide the critical amount of ROS that enables the continuity of the toxic effect of reactive species until a new synergetic reaction will happen. Indeed, this strategy can be used also as a supplementary treatment to assist some existing therapies during hypoxic conditions. A typical example is photodynamic therapy where the integration of these potentially complementary techniques provides new opportunities to improve cancer treatments. Photodynamic therapy has already transformed the standard-of-care for several malignancies. However, additional insights into the effects of external and internal radicals (generated by these two technologies) on the induction of cell death will help to advance the design of combination strategies. Conclusions This award winning treatment proposed is a promising therapeutic alternative for various cancer types. Scientific evidence show that this proposed strategy provides several advantages compared with existing treatment methods. Moreover, considering the fact that reactive oxygen species (ROS) are well known as diseases associated agents, implicated in cancer, immune diseases, infection, hart, etc, this approach, could ultimately lead to devising alternative tools for: for cancer therapy as well as applications in hospital hygiene, dental care, skin diseases, antifungal care, chronic wounds and cosmetics treatments. Combined treatment will target different key pathways in cancer cells and therefore enhance the overall therapeutic effect. Novel molecular mechanisms for modulating the concentration and subcelular activity of ROS and RNS species will be revealed. The treatment method is quite selective, meaning tunable between damage to cancer cells without damage to the normal cells which makes them safe and feasible for cancer treatment. This innovative approach allows a very accurate and a precise treatment. This treatment provides a powerful synergy in terms of reactivity, selectivity, and safety that go well beyond the simple combination of two technologies. The amount and composition of the reactive species can be completely controlled which is one of the main limitations of existing treatment methods. This novel treatment method was introduced recently and won the first price for Innovation (30.000$) at International Competition held in US, 2016.   References: Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov. 2009;8:579–91. Zhang R, et al. 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Monitoring singlet oxygen and hydroxyl radical formation with fluorescent probes during photodynamic therapy. Photochemistry and Photobiology. 2009; 85: 1177-1181.  Wang HW, Rickter E, Yuan M, Wileyto EP, Glatstein E, Yodh A, Busch TM. Effect of photosensitizer dose on fluence rate responses to photodynamic therapy. Photochemistry and Photobiology. 2007;83: 1040-1048. Frank J, Flaccus A, Schwarz C, Lambert C, Biesalski HK. Ascorbic acid suppresses cell death in rat DS-sarcoma cancer cells induced by 5-aminolevulinic acid-based photodynamic therapy. Free Radical Biology and Medicine. 2006;40: 827-836. Hadjur C, Richard MJ, Parat MO, Jardon P, Favier A. Photodynamic effects of hypericin on lipid peroxidation and antioxidant status in melanoma cells. Photochem Photobiol. 1996;64: 375-381. Laroussi M, Dobbs FC. Effects of nonequilibrium plasmas on eukaryotic cells. Report, 2009;1-18. Dewhirst MW, Cao Y, Moeller B. Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat Rev Cancer. 2008;8(6):425–37. Pani G, et al. Redox-based escape mechanism from death: the cancer lesson. Antioxid Redox Signal. 2009;11:2791–806. Harris AL. Hypoxia--a key regulatory factor in tumour growth. Nat Rev Cancer. 2002;2:38–47. Brown JM, Wilson WR. Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer. 2004;437–447. Boldogh I, Roy G, Lee MS, Bacsi A, Hazra TK, Bhakat KK, et al. Reduced DNA double strand breaks in chlorambucil resistant cells are related to high DNA-PKcs activity and low oxidative stress. Toxicology. 2003;193:137-152.   Chen J, Adikari M, Pallai R, Parekh HK, Simpkins H. Dihydrodiol dehydrogenases regulate the generation of reactive oxygen species and the development of cisplatin resistance in human ovarian carcinoma cells. Cancer Chemother Pharmacol. 2008;61: 979-987.  

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