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Posted by in Uncategorized. Copyright Procycleclothing All rights reserved. Contact Us. Buy Cheap Hydroxychloroquine Australia reviews stars based on reviews. In addition, the ideal dose, route of administration, and therapeutic schedule that should be applied in anti-cancer therapy was explored. The vast majority of preclinical studies on the effect of CQ monotherapy in cancer have reported a positive therapeutic effect, but the study parameters, doses, animal models and tumour types differ strongly between studies, complicating the interpretation of the results.

Preclinical studies investigating the effect of HCQ in cancer are limited. Therefore, follow-up in vivo studies are warranted. A risk of publication bias exists so we cannot guarantee that all negative results have been reported. Combination therapy with CQ or HCQ and existing anti-cancer therapies has been extensively studied in preclinical research, both in vitro and in vivo. The majority of these studies have reported an improved therapeutic efficacy as compared with monotherapy with existing anti-cancer drugs.

Most studies hypothesise that CQ and HCQ could increase the efficacy of other anti-cancer drugs by blocking pro-survival autophagy. Because not all studies measured autophagy levels in vivo, it is difficult to determine to what extent the other proposed mechanisms play a role. Table 2 is limited to studies that tested CQ or HCQ in combination with conventional anti-cancer agents in vivo , but there are many other combinations that have only been tested in vitro.

Finally, multiple clinical trials have investigated, or are going to investigate, the use of CQ and HCQ in different cancer types, always in combination with other anti-cancer drugs. The availability of clinical results is limited now, as most trials are still recruiting or ongoing, and those that have been completed focused primarily on safety and tolerability of CQ and HCQ in cancer. In short, these drugs have been found safe and tolerable in all completed studies and the anti-cancer effect of both compounds is promising.

However, as many clinical trials are still ongoing, a definite conclusion on the repurposing intent of CQ and HCQ in anti-cancer therapy is pending.

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Still, data from first clinical trials and additional preclinical data point to a potential positive implementation of these drugs in anti-cancer treatment. In preclinical experiments, varying CQ and HCQ doses have been used, but most of the applied doses can be extrapolated to human doses. However, whether the dose to achieve autophagy inhibition, induction of apoptosis and tumour normalisation is achievable in humans remains an open question that would require collecting additional data in humans [ ].

Clinical trials have shown that daily doses between and mg for CQ and daily doses between and mg for HCQ are safe and well tolerated, but two studies identified mg HCQ daily as the MTD. HCQ is often administered twice daily to limit plasma fluctuations and toxicity. Pascolo also suggests that timing of administration is of great importance. CQ must be administered after chemotherapy and not before, which is supported by data in a mouse model of colorectal cancer treated with gemcitabine [ ].

HCQ has been reported to have less side effects than CQ e. Currently it is not clear yet whether there are differences in anti-cancer treatment efficacy between CQ and HCQ. The clinical trials that have already been completed suggest that CQ might be more efficacious than HCQ. However, no comparative clinical trial has been set up to confirm this hypothesis. Yet, based on chemical structure, the altered safety and efficacy can be ascribed to the additional hydroxyl group in HCQ, causing pharmacokinetic differences that are essential for the working mechanism of the drugs e.

More than 30 clinical trials are currently ongoing Feb The results of these trials may indicate which tumour types are most sensitive to CQ and HCQ treatment, and which combination therapies can be beneficial. Additional preclinical studies could further characterise the most relevant mechanisms of action and their individual importance in anti-cancer therapy.

Finally, CQ analogues and other more specific autophagy inhibitory agents are also under investigation for the treatment of cancer patients e. Lys05 [ — ].

More questions?

CQ and HCQ have been studied in multiple preclinical cancer models and have demonstrated activity on several cancer-supporting pathways and in combination with a broad range of other therapies. Our review has highlighted the interesting multi-faceted actions of CQ and HCQ against cancer, making these drugs attractive for this complex disease [ , ].