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Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Oxaliplatin by itself has modest activity against advanced metastatic colorectal cancer and as an adjuvant treatment for colon cancer after resection of the primary tumor. However, in combination with fluorouracil and folinic acid (a combination known as FOLFOX) there is evidence that it improves progression-free survival, although not necessarily overall survival. This benefit is clinically relevant when cancer has spread to the locoregional lymph nodes (i.e., Stage III, Dukes C); otherwise benefit of chemotherapy is marginal.
Adjuvant Therapy of Colon Cancer
Published in Peter Sagar, Andrew G. Hill, Charles H. Knowles, Stefan Post, Willem A. Bemelman, Patricia L. Roberts, Susan Galandiuk, John R.T. Monson, Michael R.B. Keighley, Norman S. Williams, Keighley & Williams’ Surgery of the Anus, Rectum and Colon, 2019
Treatment with oxaliplatin can be considered safe according to the results of the MOSAIC study. Nevertheless, 92% of the patients suffered from a peripheral, sensitive neuropathy, and 12% of the patients were severely affected. However, the data show a complete or partial reversibility of the neuropathy in most patients. One year after the end of chemotherapy, for example, only 1% of the patients still exhibited symptoms of severe sensory neuropathy.30 However, patient information about the risk of sensitive neuropathy is crucial before adjuvant therapy with oxaliplatin is initiated. The period during which an improvement in neuropathic symptoms may occur has been described to be at least 18 months.32
Systemic therapy for appendiceal cancer
Published in Wim P. Ceelen, Edward A. Levine, Intraperitoneal Cancer Therapy, 2015
Oxaliplatin is another commonly used antineoplastic agent utilized in the systemic treatment of colorectal cancer and, therefore, commonly seen in the treatment of appendiceal cancer [23]. It is a third-generation platinum analog and a member of the alkylating agents. As an alkylating agent, oxaliplatin lends its cytotoxicity to the platinum compound that covalently binds to DNA, forming both inter- and intraplatinum–DNA cross-links. This inhibits both DNA replication and transcription, ultimately resulting in cell death [23].
Utilizing network pharmacological analysis to investigate the key targets and mechanisms of kaempferol against oxaliplatin-induced neurotoxicity
Published in Toxicology Mechanisms and Methods, 2023
Hongxing Wang, Jing Quan, Youming Deng, Jie Chen, Ke Zhang, Zhan Qu
Chemotherapy-induced peripheral neuropathic pain is a serious adverse observed in up to 80% of patients during anti-cancer drug therapy (Sisignano et al. 2014). Colorectal carcinoma is common cancer in the world. Oxaliplatin is a third-generation platinum-based anti-cancer drug, which was widely applied to treat colorectal carcinoma. Although oxaliplatin is well known for its efficacy in the treatment of colorectal cancer, it can induce severe peripheral neurotoxicity (Graham et al. 2004). This neurotoxicity can be hazardous because it could disrupt treatment plans by decreasing doses or interrupting treatment (Han et al. 2016). Neuroinflammation, glial activation, oxidative stress, mitochondrial injury, and nuclear DNA injury were considered the major mechanisms of chronic peripheral neuropathy (Xu et al. 2018; Gui et al. 2020; Kang et al. 2021). Growing evidence indicated that the activation of astrocytes plays a pro-inflammatory effect in the pathological process of neurotoxicity (Ji et al. 2014). It has been reported that the pro-inflammatory cytokine and PI3K-mTOR signal pathways lead to oxaliplatin-induced neurotoxicity (Duan et al. 2018). Besides, curcumin could improve oxaliplatin-induced neurotoxicity by mitigating neuroinflammation (Zhang et al. 2020). Astragaloside IV alleviated oxaliplatin-induced neuropathic pain via the regulation of oxidative stress and neuroinflammation (Xu et al. 2021). Therefore, suppression of neuroinflammation may be a novel treatment strategy for oxaliplatin-induced neurotoxicity.
The role of the microbiome in drug resistance in gastrointestinal cancers
Published in Expert Review of Anticancer Therapy, 2021
Ingrid Garajová, Rita Balsano, Heling Wang, Francesco Leonardi, Elisa Giovannetti, Dongmei Deng, Godefridus J. Peters
Oxaliplatin is a platinum derivative that is used in conventional chemotherapy of gastrointestinal tumors such as in the combination regimens FOLFOX (colorectal cancer) and FOLFIRINOX (pancreatic cancer). Similar to other platinum-based compounds, oxaliplatin exerts its major therapeutic effect through formation of DNA adducts resulting in DNA damage, which leads to apoptosis. Apoptosis of cancer cells can be caused by formation of these DNA lesions, arrest of DNA synthesis, inhibition of RNA synthesis, and triggering of immunologic reactions [59]. Ida et al. [60] investigated how gut microbiota influenced the efficacy of anticancer agents oxaliplatin and cisplatin in MC38 and B16 tumor-bearing mice. The researchers discovered that a healthy microbiota could enhance the efficacy of these two agents by inducing reactive oxygen species (ROS) release from myeloid cells, thereby enhancing inflammatory cytokine production and tumor regression. However, when the microbiota was eliminated by antibiotics, the efficacy of oxaliplatin was largely impaired. A similar reduction in efficacy due to the absence of resident flora was also observed in germ-free mice [60]. These results underline that cancer treatment could be improved by the modulation of human gut microbiota.
Clinical Impact of PD-L1 Expression for Survival in Curatively Resected Colon Cancer
Published in Cancer Investigation, 2020
Dong Hae Jung, Hyun Jung Park, Ho Hee Jang, Se-Hee Kim, YunJae Jung, Won-Suk Lee
We demonstrated that PD-L1 expression is associated with less aggressive cancer biology in colon cancer, which may result in better overall survival. Due to the small sample size our study did not reach statistical significance regarding overall survival. However, we demonstrated tendency toward better outcome (p = 0.175; Figure 3). This is in line with previous finding in colon cancer (32,33). The prognostic value of PD-L1 expression in colon cancer is highly debated. While some studies demonstrated with better outcome (32), others have shown a worse outcome (9,31). Although our study is in agreement with Drosser et al. (32), survival data should be interpreted with caution. In order to have a uniform study samples, we only included colon cancer and excluded rectal cancer. We believe rectal cancer is a difference disease with different tumor biology, treatment plan and prognosis. The discrepancy regarding overall survival with Masugi et al. (9) may be also due to the time of patient recruitment. This study population was enrolled between 2011 and 2014. During this time, a considerable improvement in outcome was possible with addition of oxaliplatin. This contrast with Masugi et al. (9) where more than 50% of patient population was diagnosed before 1999 and 5-FU was the main chemotherapeutic regimen at the time.