Toxicity Of Anticancer Therapy Research Articles

Targeting Nrf2 Signaling Pathway in Cancer Prevention and Treatment: The Role of Cannabis Compounds.

The development and progression of cancer are associated with the dysregulation of multiple pathways involved in cell proliferation and survival, as well as dysfunction in redox balance, immune response, and inflammation. The master antioxidant pathway, known as the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, regulates the cellular defense against oxidative stress and inflammation, making it a promising cancer prevention and treatment target. Cannabinoids have demonstrated anti-tumor and anti-inflammatory properties, affecting signaling pathways, including Nrf2. Increased oxidative stress following exposure to anti-cancer therapy prompts cancer cells to activate antioxidant mechanisms. This indicates the dual effect of Nrf2 in cancer cells-influencing proliferation and apoptotic processes and protecting against the toxicity of anti-cancer therapy. Therefore, understanding the complex role of cannabinoids in modulating Nrf2 might shed light on its potential implementation as an anti-cancer support. In this review, we aim to highlight the impact of cannabinoids on Nrf2-related factors, with a focus on cancer prevention and treatment. Additionally, we have presented the results of several research studies that combined cannabidiol (CBD) with other compounds targeting Nrf2. Further studies should be directed toward exploring the anti-inflammatory effects of cannabinoids in the context of cancer prevention and therapy.

Microbial Architects of Malignancy: Exploring the Gut Microbiome’s Influence in Cancer Initiation and Progression

The gut microbiome, a complex community of microorganisms residing in the gastrointestinal tract, has emerged as a critical player in cancer initiation and progression. This review provides an overview of the intricate interactions between the gut microbiome and cancer, exploring the underlying mechanisms and potential therapeutic implications. The gut microbiome exerts profound effects on the immune system, modulating immune responses, and chronic inflammation, which are pivotal in cancer development. In addition, it influences metabolism by altering nutrient metabolism and producing metabolites that can directly impact cellular processes related to cancer progression. Furthermore, certain gut bacteria can induce DNA damage or modify DNA repair mechanisms, contributing to the initiation and promotion of cancer. Moreover, the gut microbiome can significantly influence the effectiveness and toxicity of anticancer therapies, potentially affecting treatment outcomes. Understanding these complex interactions holds promise for the development of strategies that target the gut microbiome to prevent and treat cancer more effectively. This review emphasizes the clinical relevance of the gut microbiome in cancer, including the identification of microbial biomarkers for cancer diagnosis and prognosis. Furthermore, it discusses potential challenges and future directions for research in this rapidly evolving field. Overall, unraveling the role of the gut microbiome in cancer initiation and progression provides valuable insights for advancing personalized cancer treatment and improving patient outcomes.

Influence of chemical structure and mechanism of hydrolysis on pharmacological activity and toxicological profile of approved platinum drugs

The problems with platinum complexes are resistance and toxicity of anticancer therapy. The aim of current study is the comparison of the influence of chemical structure and mechanism of hydrolysis on pharmacological activity and toxicological profile of approved in platinum drugs: Cisplatin, Carboplatin, Oxaliplatin, Nedaplatin, Lobaplatin, Heptaplatin, Satraplatin. Hydrolysis of Carboplatin and Nedaplatin occurs by double step hydration, to obtain the same active products as with Cisplatin: diaqudiamine-platinum. The similarity in mechanisms of hydrolysis of Oxaliplatin, Lobaplatin Heptaplatin, and Satraplatin is that the first part of the hydrolysis corresponds to the ring-opening and addition of the first water molecule, and in the second step of reaction occur the loss of the ligand and the formation of the di-aquated product by the addition of a second water molecule. Cisplatin, Carboplatin, and Oxaliplatin are nephrotoxic. Cisplatin and Heptaplatin are nephrotoxic. The similar dose-limiting effects of Carboplatin, Oxaliplatin, Nedaplatin, Lobaplatin, and Satraplatin is myelosuppression.

Sex and Gender Differences in Anticancer Treatment Toxicity: A Call for Revisiting Drug Dosing in Oncology.

The practice of oncology has dramatically changed in the last decade with the introduction of molecular tumor profiling into routine tumor diagnostics and the extraordinary progress in immunotherapies. However, there remains an unmet need to explore personalized dosing strategies that take into account the patient’s sex and gender to optimize the balance between efficacy and toxicity for each individual patient. In this mini-review, we summarize the evidence on sex and gender differences in toxicity of anticancer therapies and present data on dose reduction and dose discontinuation rates for selected chemotherapies and targeted therapies. Finally, we propose the investigation of body composition (specifically fat-free muscle mass) as a viable approach for personalized treatment dosage.

Precision Oncology and Gender Medicine – Moving Forward, Slowly but Surely

Sex and gender aspects are gaining attention in oncology. Epidemiological studies show that women have reduced risk and better outcome than men in a wide range of cancer types. Melanoma is a prime example of cancer with significant female survival advantage across different stages and independent of various prognostic factors. In addition, accumulating evidence shows that women are more susceptible to the toxicity of different types of drugs. Also, considering their differences in body composition, sex-specific dosing strategies, taking into account a patient’s fat-free body mass could improve the balance between efficacy and toxicity of anticancer therapies in men and women.

Systemic Treatment of Gastroesophageal Cancer during SARS-CoV2

The SARS-CoV2 pandemic has its implications on the science and art of oncology. The morbidity and mortality associated with SARS-CoV2 are much higher compared to the general population.[1] Data regarding the toxicity of anticancer therapies and their long-term impact are emerging. We have been pushed to a point where we have to weigh the risk–benefit ratio about a particular treatment regimen. To complicate the issue, the world has gone into significant travel restrictions both at the global and local levels. With massive lockdowns affecting multiple countries, there are restrictions on travel at the domestic level and local transport facilities are not available. Hospitals are overburdened with SARS-CoV2 patients, and triaging has taken a front seat in high-volume centers. In a situation like this, many governing bodies have come up with guidelines that cater to the needs and Do's and Don'ts for cancer patients. Here, we apply our collective wisdom and formulate guidelines for treatment recommendations of gastroesophageal cancer that might be applicable for our country where there is a possibility of SARS-CoV2 cases increasing with time.

Gut microbiota, chemotherapy and the host: the influence of the gut microbiota on cancer treatment.

The gut microbiota exists in a dynamic balance between symbiosis and pathogenesis and can influence almost any aspect of host physiology. Growing evidence suggests that the gut microbiota not only plays a key role in carcinogenesis but also influences the efficacy and toxicity of anticancer therapy. The microbiota modulates the host response to chemotherapy via numerous mechanisms, including immunomodulation, xenometabolism and alteration of community structure. Furthermore, exploitation of the microbiota offers opportunities for the personalisation of chemotherapeutic regimens and the development of novel therapies. In this article, we explore the host-chemotherapeutic microbiota axis, from basic science to clinical research, and describe how it may change the face of cancer treatment.

Pulmonary toxicity of anticancer therapy from childhood Hodgkin’s lymphoma

Pulmonary toxicity is one of serious complications of combined modality treatment for malignant tumors. Issues of pulmonary toxicity after radiation therapy and bleomycin-included chemotherapy are considered in article. Pneumonitis developed after treatment divided into early and late, causing the deterioration of respiratory function. The article examines the emergence of pulmonary toxicity after radiotherapy and chemotherapy, especially with the inclusion of bleomycin. The most significant adverse effect of the bleomycin using is interstitial pneumonitis followed by pulmonary fibrosis, which is diagnosed in 46 % patients. The mortality of patients with bleomycin-induced pulmonitis is 3 %. The article describes the clinical manifestations of complications and methods of diagnosis. Bleomycin-associated pneumonitis diagnosed in 3-5 % patients receiving doses of ≤300 mg, and in 20 % patients after total doses ≥500 mg. In addition to the study of pulmonary function tests in the article the technique of performing CT of the chest with the construction of three-dimensional reconstructions using applications “Volume rendering”, allow to diagnose early and late pulmonary toxicity. The diagnostics of the late pulmonary toxicity are difficult because clinical symptoms are usually absent or expressed at moderate and low level. For timely diagnosis of this condition should be carefully controlled to an annual survey of laboratory tests, including spirometry and measurement of carbon monooxide diffusing capacity, as well as the control radiography and CT of the chest. The density gradient of the lung tissue is relatively small for the visual assessment of moderate diffuse pulmonary fibrosis, and the use of three-dimensional image allows you to improve the perception of the data, without the need for additional scanning study area.

Genetic Alteration of Keap1 Confers Constitutive Nrf2 Activation and Resistance to Chemotherapy in Gallbladder Cancer

Biliary tract cancer (BTC) is a highly malignant tumor, and identification of effective therapeutic targets to improve prognosis is urgently required. Oncogenic activation of survival genes is important for cancer cells to overcome oxidative stresses induced by their microenvironments that include chronic inflammation or exposure to anticancer drugs. We attempted to examine whether deregulation of Nrf2, a master transcriptional factor of various cytoprotective genes against oxidative stress, plays a role in the carcinogenesis of BTC. We screened genetic alteration of Keap1, a negative regulator of Nrf2, in BTC including tumors originated from gallbladder and extra- and intrahepatic bile ducts. Functional analysis of cancer-related mutant Keap1 in Nrf2 repression and the association between Nrf2 activation and resistance to 5-fluorouracil (5-FU) were investigated. Recurrent (in 1/11 cell lines and 6/53 primary tumors) Keap1 gene alterations were observed in BTC and were especially frequent (4/13, 30.7%) in gallbladder cancer (GBC). These alterations led to a considerable loss of Nrf2 repression activity, caused constitutive activation of Nrf2, and promoted cell proliferation. Down-regulation of Nrf2 activity by either Keap1 complementation or Nrf2 short interference RNA increased sensitivity to 5-FU in Keap1-altered BTC cells. Keap1 mutation occurs frequently in GBC. Aberrant Nrf2 activation provoked by Keap1 alteration is one of the molecular mechanisms for chemotherapeutic resistance in GBC and will be a novel therapeutic target as an enhancer of sensitivity to 5-FU-based regimens.

Chemotherapy in the elderly: how and for whom?

Management of cancer in the older-aged patient is an increasingly common problem in our occidental societies. Cancer is a disease primarily of older persons: over 60% of all cases of cancer are diagnosed after age 65 - an age group that constitutes less than 20% of the western population and the risk of persons over 65 years of age developing cancer is at least 10 times that of those under 65. Cancer in older persons may be considered a different disease from cancer in the younger in that way that biology of the host could influence the growth of cancer, that the management of the disease deserved an individualized approach. Indeed, the normal process of aging is associated with a progressive age-related reduction in function of many organs, including losses such as renal, pulmonary, cardiac, immune, hepatic, haematological, muscles, osseous, sight, hearing and brain functions. The consequences of these changes with age, added to comorbid diseases, have major implications on toxicities of anti-cancer therapies, surgery, radiotherapy as well as chemotherapy. However chronologic age should not be used as a guide to cancer therapy. Performance status and physiologic performance of the older patient are of prime importance to decide and conduct chemotherapy.

Restoration of wild-type conformation to full-length and truncated p53 proteins: Specific effects of ATP and ADP

Mutations in the core domain of the tumor suppressor p53 gene occur in over 50% of human cancers and are not present in normal cells hence p53 protein is a prime target for anti-cancer therapy. In full-length p53 protein, mutations have been shown to destabilise protein structure from wild-type to mutant conformation resulting in differential exposure of conformational epitopes PAb1620, PAb240 and PAb246 in murine p53 protein. In recent studies, putative anti-cancer agents have been designed for rescuing wild-type p53 conformation and function. Using full-length and truncated murine p53 proteins derived from the baculoviral system, we analysed the recovery of PAb246 and PAb1620 epitopes and have identified regions of p53 required for optimal renaturation in vitro to wild-type. The influence of ATP and ADP on the process was also determined. We demonstrate a difference in the dose-dependent effect of ATP and ADP on renaturation of full-length wildtype and monomeric p53 proteins. Putative ATP binding sites were identified at residues 1- 67 and 98-303 in conjunction with a putative ADP binding site at residues 98-303 and negative regulation of ATP/ADP binding by the proline-rich region. Improved efficacy and reduced toxicity of anti-cancer therapy may depend upon compounds engineered to rescue hot-spot core mutations in the context of full-length p53.