Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.0
4.5
Journals
Cancers
Special Issues
Efforts to Mitigate the Toxicity of Cancer Therapeutics
share announcement

Efforts to Mitigate the Toxicity of Cancer Therapeutics

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 January 2021) | Viewed by 17056

Special Issue Editor

Prof. Dr. David A. Gewirtz

E-Mail Website
Guest Editor
Department of Pharmacology and Toxicology and Medicine, Virginia Commonwealth University, Richmond, VA 23284, USA
Interests: cancer chemotherapy; radiotherapy; autophagy; senescence; apoptosis

Special Issue Information

With improvements in cancer therapeutics that have extended the lives of cancer patients, it becomes critical to also consider the impact of these treatments on patient quality of life. The toxicities of both cancer chemotherapeutic drugs and radiation therapy include peripheral neuropathy (vinca alkaloids, taxanes, platinum compounds and bortezomib), chemobrain (various drugs alone and in combination), arthralgia (aromatase inhibitors), delayed cardiotoxicity (doxorubicin), renal injury (platinum compounds), fibrosis (radiation) and severe delayed onset diarrhea (irinotecan), among others. With some exceptions, the basis for these toxicities is uncertain and there are few, if any, useful approaches for preventing or treating these “side effects”. The goals of this special issue are to explore the progress of current research efforts to mitigate the toxic and often severe and persistent impact of current standard of care therapies in cancer.

Prof. Dr. David A. Gewirtz
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cancer therapeutics
  • radiation therapy
  • peripheral neuropathy
  • arthralgia
  • renal injury
  • chemobrain
  • cardiotoxicity
  • fibrosis

Published Papers (5 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

12 pages, 1621 KiB  
Article
Predicting Radiotherapy Impact on Late Bladder Toxicity in Prostate Cancer Patients: An Observational Study
by Francesco Catucci, Anna Rita Alitto, Carlotta Masciocchi, Nicola Dinapoli, Roberto Gatta, Antonella Martino, Ciro Mazzarella, Bruno Fionda, Vincenzo Frascino, Antonio Piras, Andrea D’Aviero, Francesco Preziosi, Giovanni Palazzoni, Vincenzo Valentini and Giovanna Mantini
Cancers 2021, 13(2), 175; https://doi.org/10.3390/cancers13020175 - 6 Jan 2021
Cited by 9 | Viewed by 2458
Abstract
Background and purpose: The aim of our study was to elaborate a suitable model on bladder late toxicity in prostate cancer (PC) patients treated by radiotherapy with volumetric technique. Materials and methods: PC patients treated between September 2010 and April 2017 were included [...] Read more.
Background and purpose: The aim of our study was to elaborate a suitable model on bladder late toxicity in prostate cancer (PC) patients treated by radiotherapy with volumetric technique. Materials and methods: PC patients treated between September 2010 and April 2017 were included in the analysis. An observational study was performed collecting late toxicity data of any grade, according to RTOG and CTCAE 4.03 scales, cumulative dose volumes histograms were exported for each patient. Vdose, the value of dose to a specific volume of organ at risk (OAR), impact was analyzed through the Mann–Whitney rank-sum test. Logistic regression was used as the final model. The model performance was estimated by taking 1000 samples with replacement from the original dataset and calculating the AUC average. In addition, the calibration plot (Hosmer–Lemeshow goodness-of-fit test) was used to evaluate the performance of internal validation. RStudio Software version 3.3.1 and an in house developed software package “Moddicom” were used. Results: Data from 175 patients were collected. The median follow-up was 39 months (min–max 3.00–113.00). We performed Mann–Whitney rank-sum test with continuity correction in the subset of patients with late bladder toxicity grade ≥ 2: a statistically significant p-value with a Vdose of 51.43 Gy by applying a logistic regression model (coefficient 4.3, p value 0.025) for the prediction of the development of late G ≥ 2 GU toxicity was observed. The performance for the model’s internal validation was evaluated, with an AUC equal to 0.626. Accuracy was estimated through the elaboration of a calibration plot. Conclusions: Our preliminary results could help to optimize treatment planning procedures and customize treatments. Full article
(This article belongs to the Special Issue Efforts to Mitigate the Toxicity of Cancer Therapeutics)
►▼ Show Figures

Figure 1

21 pages, 4981 KiB  
Article
A Fenofibrate Diet Prevents Paclitaxel-Induced Peripheral Neuropathy in Mice
by Martial Caillaud, Nipa H. Patel, Wisam Toma, Alyssa White, Danielle Thompson, Jared Mann, Tammy H. Tran, Jane L. Roberts, Justin L. Poklis, John W. Bigbee, Xianjun Fang, David A. Gewirtz and M. Imad Damaj
Cancers 2021, 13(1), 69; https://doi.org/10.3390/cancers13010069 - 29 Dec 2020
Cited by 14 | Viewed by 3826
Abstract
Background: Paclitaxel-induced peripheral neuropathy (PIPN) is a major adverse effect of this chemotherapeutic agent that is used in the treatment of a number of solid malignancies. PIPN leads notably to burning pain, cold and mechanical allodynia. PIPN is thought to be a consequence [...] Read more.
Background: Paclitaxel-induced peripheral neuropathy (PIPN) is a major adverse effect of this chemotherapeutic agent that is used in the treatment of a number of solid malignancies. PIPN leads notably to burning pain, cold and mechanical allodynia. PIPN is thought to be a consequence of alterations of mitochondrial function, hyperexcitability of neurons, nerve fiber loss, oxidative stress and neuroinflammation in dorsal root ganglia (DRG) and spinal cord (SC). Therefore, reducing neuroinflammation could potentially attenuate neuropathy symptoms. Peroxisome proliferator-activated receptor-α (PPAR-α) nuclear receptors that modulate inflammatory responses can be targeted by non-selective agonists, such as fenofibrate, which is used in the treatment of dyslipidemia. Methods: Our studies tested the efficacy of a fenofibrate diet (0.2% and 0.4%) in preventing the development of PIPN. Paclitaxel (8 mg/kg) was administered via 4 intraperitoneal (i.p.) injections in C57BL/6J mice (both male and female). Mechanical and cold hypersensitivity, wheel running activity, sensory nerve action potential (SNAP), sciatic nerve histology, intra-epidermal fibers, as well as the expression of PPAR-α and neuroinflammation were evaluated in DRG and SC. Results: Fenofibrate in the diet partially prevented the development of mechanical hypersensitivity but completely prevented cold hypersensitivity and the decrease in wheel running activity induced by paclitaxel. The reduction in SNAP amplitude induced by paclitaxel was also prevented by fenofibrate. Our results indicate that suppression of paclitaxel-induced pain by fenofibrate involves the regulation of PPAR-α expression through reduction in neuroinflammation. Finally, co-administration of paclitaxel and the active metabolite of fenofibrate (fenofibric acid) did not interfere with the suppression of tumor cell growth or clonogenicity by paclitaxel in ovarian and breast cancer cell lines. Conclusions: Taken together, our results show the therapeutic potential of fenofibrate in the prevention of PIPN development. Full article
(This article belongs to the Special Issue Efforts to Mitigate the Toxicity of Cancer Therapeutics)
►▼ Show Figures

Figure 1

20 pages, 12268 KiB  
Article
Fertility Preservation in Childhood Cancer: Endocrine Activity in Prepubertal Human Testis Xenografts Exposed to a Pubertal Hormone Environment
by Marsida Hutka, Prashant Kadam, Dorien Van Saen, Natalie Z. M. Homer, Jaime Onofre, W. Hamish B. Wallace, Lee B. Smith, Jan-Bernd Stukenborg, Ellen Goossens and Rod T. Mitchell
Cancers 2020, 12(10), 2830; https://doi.org/10.3390/cancers12102830 - 30 Sep 2020
Cited by 8 | Viewed by 3675
Abstract
Survivors of childhood cancer are at risk for long-term treatment-induced health sequelae, including gonadotoxicity and iatrogenic infertility. At present, for prepubertal boys there are no viable clinical options to preserve future reproductive potential. We investigated the effect of a pubertal induction regimen with [...] Read more.
Survivors of childhood cancer are at risk for long-term treatment-induced health sequelae, including gonadotoxicity and iatrogenic infertility. At present, for prepubertal boys there are no viable clinical options to preserve future reproductive potential. We investigated the effect of a pubertal induction regimen with gonadotrophins on prepubertal human testis xenograft development. Human testis tissue was obtained from patients with cancer and non-malignant haematological disorders (n = 6; aged 1–14 years) who underwent testis tissue cryopreservation for fertility preservation. Fresh and frozen-thawed testis fragments were transplanted subcutaneously or intratesticularly into immunocompromised mice. Graft-bearing mice received injections of vehicle or exogenous gonadotrophins, human chorionic gonadotrophin (hCG, 20 IU), and follicle-stimulating hormone (FSH, 12.5 IU) three times a week for 12 weeks. The gross morphology of vehicle and gonadotrophin-exposed grafts was similar for both transplantation sites. Exposure of prepubertal human testis tissue xenografts to exogenous gonadotrophins resulted in limited endocrine function of grafts, as demonstrated by the occasional expression of the steroidogenic cholesterol side-chain cleavage enzyme (CYP11A1). Plasma testosterone concentrations (0.13 vs. 0.25 ng/mL; p = 0.594) and seminal vesicle weights (10.02 vs. 13.93 mg; p = 0.431) in gonadotrophin-exposed recipient mice were comparable to vehicle-exposed controls. Regardless of the transplantation site and treatment, initiation and maintenance of androgen receptor (AR) expression were observed in Sertoli cells, indicating commitment towards a more differentiated status. However, neither exogenous gonadotrophins (in castrated host mice) nor endogenous testosterone (in intact host mice) were sufficient to repress the expression of markers associated with immature Sertoli cells, such as anti-Müllerian hormone (AMH) and Ki67, or to induce the redistribution of junctional proteins (connexin 43, CX43; claudin 11, CLDN11) to areas adjacent to the basement membrane. Spermatogonia did not progress developmentally but remained the most advanced germ cell type in testis xenografts. Overall, these findings demonstrate that exogenous gonadotrophins promote partial activation and maturation of the somatic environment in prepubertal testis xenografts. However, alternative hormone regimens or additional factors for pubertal induction are required to complete the functional maturation of the spermatogonial stem cell (SSC) niche. Full article
(This article belongs to the Special Issue Efforts to Mitigate the Toxicity of Cancer Therapeutics)
►▼ Show Figures

Figure 1

17 pages, 3845 KiB  
Article
Supplementary Oral Anamorelin Mitigates Anorexia and Skeletal Muscle Atrophy Induced by Gemcitabine Plus Cisplatin Systemic Chemotherapy in a Mouse Model
by Makito Miyake, Shunta Hori, Yoshitaka Itami, Yuki Oda, Takuya Owari, Tomomi Fujii, Sayuri Ohnishi, Yosuke Morizawa, Daisuke Gotoh, Yasushi Nakai, Satoshi Anai, Kazumasa Torimoto, Nobumichi Tanaka and Kiyohide Fujimoto
Cancers 2020, 12(7), 1942; https://doi.org/10.3390/cancers12071942 - 17 Jul 2020
Cited by 14 | Viewed by 3343
Abstract
Chemotherapy-induced adverse effects can reduce the relative dose intensity and quality of life. In this study, we investigated the potential benefit of supplementary anamorelin and 5-aminolevulinic acid (5-ALA) as preventive interventions against a gemcitabine and cisplatin (GC) combination chemotherapy-induced adverse effects in a [...] Read more.
Chemotherapy-induced adverse effects can reduce the relative dose intensity and quality of life. In this study, we investigated the potential benefit of supplementary anamorelin and 5-aminolevulinic acid (5-ALA) as preventive interventions against a gemcitabine and cisplatin (GC) combination chemotherapy-induced adverse effects in a mouse model. Non-cancer-bearing C3H mice were randomly allocated as follows and treated for 2 weeks—(1) non-treated control, (2) oral anamorelin alone, (3) oral 5-ALA alone, (4) gemcitabine and cisplatin (GC) chemotherapy, (5) GC plus anamorelin, and (6) GC plus 5-ALA. GC chemotherapy significantly decreased body weight, food intake, skeletal muscle mass and induced severe gastric mucositis, which resulted in decreased ghrelin production and blood ghrelin level. The supplementation of oral anamorelin to GC chemotherapy successfully mitigated decrease of food intake during the treatment period and body weight loss at day 8. In addition, analysis of the resected muscles and stomach revealed that anamorelin suppressed chemotherapy-induced skeletal muscle atrophy by mediating the downregulation of forkhead box protein O-1 (FOXO1)/atrogin-1 signaling and gastric damage. Our findings suggest the preventive effect of anamorelin against GC combination chemotherapy, which was selected for patients with some types of advanced malignancies in clinical practice. Full article
(This article belongs to the Special Issue Efforts to Mitigate the Toxicity of Cancer Therapeutics)
►▼ Show Figures

Figure 1

Review

Jump to: Research

21 pages, 276 KiB  
Review
Renal and Cardiovascular Toxicities by New Systemic Treatments for Prostate Cancer
by Giuseppe Saltalamacchia, Mara Frascaroli, Antonio Bernardo and Erica Quaquarini
Cancers 2020, 12(7), 1750; https://doi.org/10.3390/cancers12071750 - 1 Jul 2020
Cited by 10 | Viewed by 3027
Abstract
Prostate cancer (PC) is the most common male cancer in Western Countries. In recent years, the treatment of relapsed or metastatic disease had benefited by the introduction of a variety of new different drugs. In consideration of the relative long survival of PC [...] Read more.
Prostate cancer (PC) is the most common male cancer in Western Countries. In recent years, the treatment of relapsed or metastatic disease had benefited by the introduction of a variety of new different drugs. In consideration of the relative long survival of PC patients, side effects of these drugs must be considered and monitored. In this review, we analyzed the newly developed therapies for PC treatment, describing the mechanism of action, the metabolism and latest clinical trials that led to the approval of these drugs in clinical practice. We then evaluated the cardiovascular and renal side effects from pivotal phase III and II studies and meta-analyses. Cardiovascular side effects are the most frequent, in particular hypertension, while renal toxicity is rarer and not well described in literature. Therefore, there is a need to better define the effects of these therapies, in order to personalize patient treatment on the basis of their comorbidities and preferences, in addition to their symptoms and disease load. Full article
(This article belongs to the Special Issue Efforts to Mitigate the Toxicity of Cancer Therapeutics)
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-5
Back to TopTop