1,721,179 research outputs found
An update on promising agents for the treatment of cancer cachexia
No full textPURPOSE OF REVIEW: There are no published conclusive phase III controlled clinical trials nor general consensus about treatment approaches despite several years of coordinated efforts in basic and clinical research. Consequently, practice guidelines for the prevention and treatment of cancer-related muscle wasting are lacking. The purpose of this review is to supply an update on the promising agents and/or combined approaches for the treatment of cancer cachexia.
RECENT FINDINGS: The choice for cancer cachexia treatment in clinical practice is very limited: the only approved drugs in Europe are progestagens. Several drugs with a strong rationale have failed or have not shown univocal results in clinical trials: they include eicosapentaenoic acid, cannabinoids, bortezomib and anti-tumor necrosis factor (TNF)-alpha monoclonal antibody. Several emerging drugs have shown promising results but are still under clinical investigation [thalidomide, selective cyclooxygenase (COX)-2 inhibitors, ghrelin mimetics, oxandrolone, olanzapine]. Moreover, increasing knowledge of cachexia pathophysiology and preliminary clinical findings seem to suggest that a combined treatment approach may be the most effective option.
SUMMARY: A number of promising new agents are currently being developed but are not as yet regarded as standard of care. They include: selective COX-2 inhibitors, ghrelin mimetics, oxandrolone, selective androgen receptor modulators (ostarine), olanzapine, anti-IL-6 antibody and an innovative approach of multitargeted combined treatment. The data reported seem to suggest that the most effective treatment for cancer cachexia may be a combination regimen rather than single-agent treatments. This is in keeping with the general consensus that cancer cachexia is a multifactorial process and, hence, a potentially effective approach should be multimoda
Cyclooxygenase-2 inhibitors and antioxidants in the treatment of cachexia
No full textPURPOSE OF REVIEW: Cancer cachexia is increasingly becoming a critical component in the comprehensive approach to cancer patients influencing morbidity, mortality and quality of life. Therefore its pathophysiology and the main contributing factors have been investigated with the aim of developing effective therapies. Reported findings highlight the role of chronic inflammation and oxidative stress in the onset of cancer cachexia.
RECENT FINDINGS: Chronic inflammation, one of the main features of cancer cachexia, triggers the overproduction of proinflammatory cytokines playing a major role in the pathogenesis of systemic symptoms of cachexia; therefore, antiinflammatory drugs such as cyclooxygenase-2 inhibitors could break the 'vicious circle' leading to the onset and worsening of this devastating syndrome. Likewise, oxidative stress, almost always accompanying cancer cachexia, may be counteracted by effective antioxidant treatments. The most relevant recent clinical approaches addressing these targets are reported.
SUMMARY: Fairly advanced clinical data on efficacy of cyclooxygenase-2 inhibitors and antioxidants in advanced cancer patients are promising, but the best way to administer and combine them with other agents, the optimal dose and timing remain uncertain. However, because cachexia is a multifactorial syndrome, therapeutic approaches targeting a single contributing factor may be inadequate. A rational treatment should thus be multitargeted addressing all key contributing factors
Cisplatin : an old drug with a newfound efficacy -- from mechanisms of action to cytotoxicity
No full textIntroduction: Cisplatin is a highly effective antineoplastic drug with an extremely current mechanism of action. Cisplatin-induced side effects are dose-dependent and limit the administration of increased dosages, thus compromising its therapeutic efficacy. Areas covered: This review aims to describe the emerging knowledge about the biochemical mechanisms that mediate cisplatin cytotoxicity and side effects. A specific section is devoted to discuss the pathogenesis of cisplatin-related toxicities and the potential measures to counteract them. Expert opinion: Although cisplatin has been used for a long time, only recently its exact mechanism of action has been better defined. The cytotoxic activity of cisplatin is largely dependent on the glycolytic metabolism of tumor cells: cisplatin redirects cancer cells to oxidative phosphorylation from the 'Warburg effect', which is considered one of the most important mechanisms of tumor cell survival. The interference of cisplatin with glucose metabolism is also a cause of its relevant toxicities. The emerging knowledge on the complex mechanisms, which mediate cisplatin cytotoxicity and side effect, may lead to a more appropriate and safe use of this drug. Further studies are warranted to define and implement its effectiveness in combination with targeted drugs able to interfere with cellular energy metabolism, such as mTOR inhibitors
Cancer is not a guest
Full text linkIn a recent article titled "Embracing Cancer Complexity: Hallmarks of Systemic Disease" published in Cell, Swaton et al. propose the idea of cancer as a guest that develops within a host. They discuss the possible causes and events of neoplastic cell dysregulations within an organism, highlighting events such as cachexia and thrombosis. However, we believe that to understand cancer-associated phenomena better, cancer cannot be considered a guest. In reality, cancer is born, develops, and spreads within its environment. It does not come from outside but instead uses the same system in which it lives to promote its death plan. Indeed, today we know that cancer not only causes local symptoms in the affected organ but also leads to systemic symptoms, which are evidence of inflammation associated with cancer. Inflammation is vital in controlling oncogenesis and neoplastic proliferation during the resistance phase, which is a critical moment for the immune system to demonstrate its effectiveness. However, if the immune system causes immunopathological damage, it may lead to necrosis and eventually to the tolerance phase, which can result in systemic symptoms. Understanding these phenomena thoroughly explains thrombophilia, anemia, sarcopenia, and iron metabolism disruption in advanced-stage neoplastic patients. The concept of the microenvironment takes on a different meaning in this context. The same cells that should oppose cancer in the tolerance phase now participate in a process that self-maintains, favoring the growth of the cancer and its death plan. The exact knowledge of these mechanisms is a more modern translational approach to treating cancer and its related symptoms
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