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Oxidative stress results from a persistent imbalance in oxidation levels that promotes oxidants, playing a crucial role in the early and sustained phases of DNA damage and genomic and epigenetic instability, both of which are intricately linked to the development of tumors. The molecular pathways contributing to carcinogenesis in this context, particularly those related to double-strand and single-strand breaks in DNA, serve as indicators of DNA damage due to oxidation in cancer cases, as well as factors contributing to epigenetic instability through ectopic expressions. Oxidative stress has been considered a therapeutic target for many years, and an increasing number of studies have highlighted the promising effectiveness of natural products in cancer treatment. In this regard, we present significant research on the therapeutic targeting of oxidative stress using natural molecules and underscore the essential role of oxidative stress in cancer. The consequences of stress, especially epigenetic instability, also offer significant therapeutic prospects. In this context, the use of natural epi-drugs capable of modulating and reorganizing the epigenetic network is beginning to emerge remarkably. In this review, we emphasize the close connections between oxidative stress, epigenetic instability, and tumor transformation, while highlighting the role of natural substances as antioxidants and epi-drugs in the anti-tumoral context., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Panobinostat, also known as Farydak®, LBH589, PNB, or panobinostat lactate, is a hydroxamic acid that has been approved by the Food and Drug Administration (FDA) for its anti-cancer properties. This orally bioavailable drug is classified as a non-selective histone deacetylase inhibitor (pan-HDACi) that inhibits class I, II, and IV HDACs at nanomolar levels due to its significant histone modifications and epigenetic mechanisms. A mismatch between histone acetyltransferases (HATs) and HDACs can negatively affect the regulation of the genes concerned, which in turn can contribute to tumorigenesis. Indeed, panobinostat inhibits HDACs, potentially leading to acetylated histone accumulation, re-establishing normal gene expression in cancer cells, and helping to drive multiple signaling pathways. These pathways include induction of histone acetylation and cytotoxicity for the majority of tested cancer cell lines, increased levels of p21 cell cycle proteins, enhanced amounts of pro-apoptotic factors (such as caspase-3/7 activity and cleaved poly (ADP-ribose) polymerase (PARP)) associated with decreased levels of anti-apoptotic factors [B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra-large (Bcl-XL)], as well as regulation of immune response [upregulated programmed death-ligand 1 (PD-L1) and interferon gamma receptor 1 (IFN-γR1) expression] and other events. The therapeutic outcome of panobinostat is therefore mediated by sub-pathways involving proteasome and/or aggresome degradation, endoplasmic reticulum, cell cycle arrest, promotion of extrinsic and intrinsic processes of apoptosis, tumor microenvironment remodeling, and angiogenesis inhibition. In this investigation, we aimed to pinpoint the precise molecular mechanism underlying panobinostat's HDAC inhibitory effect. A more thorough understanding of these mechanisms will greatly advance our knowledge of cancer cell aberrations and, as a result, provide an opportunity for the discovery of significant new therapeutic perspectives through cancer therapeutics., Competing Interests: Declaration of Competing Interest Please declare any financial or personal interests that might be potentially viewed to influence the work presented. Interests could include consultancies, honoraria, patent ownership or other. If there are none state ‘there are none’., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Breakthrough pain is an exacerbation of pain occurring in patients with chronic pain who receive opioid therapy every day. Breakthrough pain has not been routinely recognized, evaluated and treated. This study aimed to analyze the utilization of opiates analgesics, including dose regimentation, frequency of use, and the actual adverse effects in cancer patients with breakthrough pain., Methods: Data were collected by the retrospective method in the period from January to December 2017. Patients involved received opioids around the clock for treating background pain and rescue medication for treating breakthrough pain. The percentage of the rescue medication dose was calculated based on the total daily opioid dose to treat background pain. Descriptive analysis was used., Results: From 335 visits, there were 334 of patient visit where the patient received immediate-release morphine as a rescue medication with a dose percentage between 6.67-60%, and 1 visit where the patient received codeine with a dose percentage of 16.67%. Of 335 visits, 233 patient visits received the right proportion of opioid rescue medication doses, while 102 patient visits received a greater dose proportion than the recommended dose of 5-20%., Conclusions: Immediate-release morphine is the most commonly prescribed analgesic to treat breakthrough pain and used at 6.67-60% of daily dose with the frequency of use between 2 to 6 times a day. There were 189 (56.42%) patient visits when the patient experienced the adverse effects of the opioid. The identified actual adverse effects are constipation, nausea, and vomiting.