The Link between Conventional and Novel Anti-Cancer Therapeutics with Thrombotic Microangiopathy

2021 ◽  
Vol 14 ◽  
Author(s):  
Carmen Elena Cervantes ◽  
Sam Kant ◽  
Mohamed Atta
Keyword(s):  
Kidney Disease ◽  
Thrombotic Microangiopathy ◽  
Cancer Therapeutics ◽  
Chemotherapeutic Agents ◽  
Cancer Therapies ◽  
Drug Induced ◽  
Anti Cancer ◽  
Poor Nutritional Status ◽  
Dose Dependent ◽  
Pathophysiologic Mechanisms

Background: Kidney disease associated with cancer and anti-cancer therapies has been increasingly recognized in the field of Onco-nephrology. In particular, drug-induced nephrotoxicity has necessary implications since most chemotherapeutic agents have nephrotoxic potential. Also, standard creatinine clearance methods used to measure kidney function have been questioned in cancer patients due to factors like low muscle mass and poor nutritional status. Overestimations of the glomerular filtration rate not only increase the nephrotoxic potential of different agents but also can further limit the use of first-line therapies. Objective: This review covers drug-induced thrombotic microangiopathy explicitly. It has two pathophysiologic mechanisms, including immune or idiosyncratic reactions and non-immune or dose-dependent ones. Conclusion: As novel cancer therapies are developed, it is paramount to understand better conventional and novel chemotherapeutic agents and their role in kidney disease.

scholarly journals Potential Role of Ginseng in the Treatment of Colorectal Cancer

2008 ◽  
Vol 36 (06) ◽  
pp. 1019-1028 ◽  
Author(s):  
Chong-Zhi Wang ◽  
Chun-Su Yuan
Keyword(s):  
Colorectal Cancer ◽  
Cancer Therapeutics ◽  
Chemotherapeutic Agents ◽  
Cancer Therapies ◽  
Chemical Structures ◽  
Time Treatment ◽  
Anti Cancer ◽  
The Us ◽  
Pharmacologically Active

Colorectal cancer remains one of the most prevalent cancer and a leading cause of cancer related death in the US. Many currently used chemotherapeutic agents are derived from botanicals. Identifying herbal sources, including those from ginseng family, to develop better anti-cancer therapies remains an essential step in advancing the treatment of the cancer. In this article, potential roles of ginseng herbs, especially American ginseng and notoginseng, in colorectal cancer therapeutics are presented. The major pharmacologically active constituents of ginsengs are ginsenosides, which can be mainly classified as protopanaxadiol and protopanaxatriol groups. Structure-activity relationship between their chemical structures and pharmacological activities are discussed. In addition, various steaming temperature and time treatment of the ginseng herbs can change ginsenoside profiles, and enhance their anti-cancer activities. This heat treatment process may increase the role of ginseng in treating colorectal cancer.

Breast Cancer Therapeutics Based on Fusarochromanone and EGFR Inhibitors

2021 ◽  
Author(s):  
Natalie Carroll ◽  
Alena Smith ◽  
Brian A. Salvatore ◽  
Elahe Mahdavian
Keyword(s):  
Breast Cancer ◽  
Mode Of Action ◽  
Cancer Therapeutics ◽  
Egfr Inhibitors ◽  
Cancer Therapies ◽  
Racemic Form ◽  
Combination Treatments ◽  
Anti Cancer ◽  
Cancer Agent ◽  
Cancer Activity

Abstract Background: Fusarochromanone (FC101) is a small molecule with potent anti-cancer activity. It was originally derived from the fungal plant pathogen, Fusarium equiseti, and it has also been synthesized in non-racemic form in our lab. Numerous studies reveal the promising biological activity of FC101, including potent anti-angiogenic and anti-cancer activity. While FC101 is potent as a single drug treatment across many cancer cell lines, current cancer therapies often incorporate a combination of drugs in order to increase efficacy and decrease the development of drug resistance. In this study, we leverage drug combinations and cellular phenotypic screens to address important questions about FC101’s mode of action and its potential synergies as an anti-cancer therapeutic agent in triple negative breast cancer (TNBC).Method: We hypothesized that FC101’s activity against TNBC is similar to the known mTOR inhibitor, everolimus, because FC101 reduces the phosphorylation of two key mTOR substrates, S6K and S6. Since everolimus synergistically enhances the anti-cancer activities of known EGFR inhibitors (erlotinib or lapatinib) in TNBC, we performed analogous studies with FC101. Phenotypic cellular assays helped assess whether FC101 (in both single and combination treatments) acts similarly to everolimus.Results: FC101 outperformed all other single treatments in both cell proliferation and viability assays. Unlike everolimus, however, FC101 brought about a sustained decrease in cell viability in drug washout studies. None of the other drugs were able to maintain comparable effects upon removal of the treatment agents. Although we observed slightly additive effects when the TNBC cells were treated with FC101 and either EGFR inhibitor, those effects were not truly synergistic in the manner displayed with everolimus. Conclusion: Our results rule out direct inhibition of mTOR by FC101 and suggest that FC101 acts through a different mechanism than everolimus. This lays the foundation for the refinement of our hypothesis in order to better understand FC101’s mode of action as a novel anti-cancer agent.

The Complex Cancer Care Coverage Environment — What is the Role of Legislation?

2020 ◽  
Vol 48 (3) ◽  
pp. 538-551 ◽  
Author(s):  
Christine Leopold ◽  
Rebecca L. Haffajee ◽  
Christine Y. Lu ◽  
Anita K. Wagner
Keyword(s):  
Cancer Care ◽  
Insurance Coverage ◽  
Cancer Therapeutics ◽  
Health Insurance Coverage ◽  
Cancer Therapies ◽  
Cancer Treatments ◽  
Difficult Situation ◽  
Cell Therapies ◽  
State Laws ◽  
Anti Cancer

Over the past decades, anti-cancer treatments have evolved rapidly from cytotoxic chemotherapies to targeted therapies including oral targeted medications and injectable immunooncology and cell therapies. New anti-cancer medications come to markets at increasingly high prices, and health insurance coverage is crucial for patient access to these therapies. State laws are intended to facilitate insurance coverage of anti-cancer therapies.Using Massachusetts as a case study, we identified five current cancer coverage state laws and interviewed experts on their perceptions of the relevance of the laws and how well they meet the current needs of cancer care given rapid changes in therapies. Interviewees emphasized that cancer therapies, as compared to many other therapeutic areas, are unique because insurance legislation targets their coverage. They identified the oral chemotherapy parity law as contributing to increasing treatment costs in commercial insurance. For commercial insurers, coverage mandates combined with the realities of new cancer medications — including high prices and often limited evidence of efficacy at approval — compound a difficult situation. Respondents recommended policy approaches to address this challenging coverage environment, including the implementation of closed formularies, the use of cost-effectiveness studies to guide coverage decisions, and the application of value-based pricing concepts. Given the evolution of cancer therapeutics, it may be time to evaluate the benefits and challenges of cancer coverage mandates.

scholarly journals An in vitro quantitative systems pharmacology approach for deconvolving mechanisms of drug-induced, multilineage cytopenias

2019 ◽  
Author(s):  
Jennifer L. Wilson ◽  
Dan Lu ◽  
Nick Corr ◽  
Aaron Fullerton ◽  
James Lu
Keyword(s):  
Blood Cell ◽  
Drug Effects ◽  
Cell Killing ◽  
Cancer Therapies ◽  
Systems Pharmacology ◽  
Drug Induced ◽  
Quantitative Systems Pharmacology ◽  
Cell Lineages ◽  
Anti Cancer

AbstractMyelosuppression is one of the most common and severe adverse events associated with anti-cancer therapies and can be a source of drug attrition. Current mathematical modeling methods for assessing cytopenia risk rely on indirect measurements of drug effects and primarily focus on single lineage responses to drugs. However, anti-cancer therapies have diverse mechanisms with varying degrees of effect across hematopoietic lineages. To improve predictive understanding of drug-induced myelosuppression, we developed a quantitative systems pharmacology (QSP) model of hematopoiesis in vitro for quantifying the effects of anti-cancer agents on multiple hematopoietic cell lineages. We calibrated the system parameters of the model to cell kinetics data without treatment and then validated the model by showing that the inferred mechanisms of anti-proliferation and/or cell-killing are consistent with the published mechanisms for three classes of drugs with different mechanisms of action. Using a set of compounds as a sample set, we then analyzed novel compounds to predict their mechanisms and magnitude of myelosuppression. Further, these quantitative mechanisms are valuable for the development of translational in vivo models to predict clinical cytopenia effects.Author SummaryReduced bone marrow activity and levels of mature blood cells is an undesirable side effect of many anti-cancer therapies. Selecting promising lead compounds for further development requires understanding of potential myelosuppressive effects. However, existing preclinical experiments and modeling formulations fail to consider drug effects on multiple blood cell types or the mechanistic differences between how drugs induced myelosuppression. Here we developed a quantitative systems pharmacology (QSP) model that estimates a drug candidate’s effect on multiple precursor and mature blood cell lineages and further distinguishes how the drug affects these populations - through cell-killing or anti-proliferation mechanisms. This modeling formalism is valuable for vetting compounds for therapeutic development and for further translational modeling to anticipate the clinical effects of compounds.

scholarly journals DNA Repair Pathways in Cancer Therapy and Resistance

2021 ◽  
Vol 11 ◽  
Author(s):  
Lan-ya Li ◽  
Yi-di Guan ◽  
Xi-sha Chen ◽  
Jin-ming Yang ◽  
Yan Cheng
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Mammalian Cells ◽  
Chemotherapeutic Agents ◽  
Cancer Therapies ◽  
Exogenous Dna ◽  
Dna Damaging Agents ◽  
Anti Cancer ◽  
Mitochondria Dna ◽  
Repair Pathways

DNA repair pathways are triggered to maintain genetic stability and integrity when mammalian cells are exposed to endogenous or exogenous DNA-damaging agents. The deregulation of DNA repair pathways is associated with the initiation and progression of cancer. As the primary anti-cancer therapies, ionizing radiation and chemotherapeutic agents induce cell death by directly or indirectly causing DNA damage, dysregulation of the DNA damage response may contribute to hypersensitivity or resistance of cancer cells to genotoxic agents and targeting DNA repair pathway can increase the tumor sensitivity to cancer therapies. Therefore, targeting DNA repair pathways may be a potential therapeutic approach for cancer treatment. A better understanding of the biology and the regulatory mechanisms of DNA repair pathways has the potential to facilitate the development of inhibitors of nuclear and mitochondria DNA repair pathways for enhancing anticancer effect of DNA damage-based therapy.

scholarly journals Cancer Treatment Goes Viral: Using Viral Proteins to Induce Tumour-Specific Cell Death

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1975 ◽  
Author(s):  
Jasmine Wyatt ◽  
Manuel M. Müller ◽  
Mahvash Tavassoli
Keyword(s):  
Cell Death ◽  
Cancer Treatment ◽  
Current Knowledge ◽  
Cancer Therapeutics ◽  
Viral Proteins ◽  
Chemotherapeutic Agents ◽  
Tumour Cells ◽  
Specific Cell ◽  
Cancer Therapies ◽  
The Past

Cell death is a tightly regulated process which can be exploited in cancer treatment to drive the killing of the tumour. Several conventional cancer therapies including chemotherapeutic agents target pathways involved in cell death, yet they often fail due to the lack of selectivity they have for tumour cells over healthy cells. Over the past decade, research has demonstrated the existence of numerous proteins which have an intrinsic tumour-specific toxicity, several of which originate from viruses. These tumour-selective viral proteins, although from distinct backgrounds, have several similar and interesting properties. Though the mechanism(s) of action of these proteins are not fully understood, it is possible that they can manipulate several cell death modes in cancer exemplifying the intricate interplay between these pathways. This review will discuss our current knowledge on the topic and outstanding questions, as well as deliberate the potential for viral proteins to progress into the clinic as successful cancer therapeutics.

scholarly journals Chemoprotective and chemosensitizing effects of apigenin on cancer therapy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zahra Nozhat ◽  
Shabnam Heydarzadeh ◽  
Zahra Memariani ◽  
Amirhossein Ahmadi
Keyword(s):  
Drug Resistance ◽  
Clinical Trials ◽  
Side Effects ◽  
Combination Therapy ◽  
Molecular Mechanisms ◽  
Cancer Therapeutics ◽  
Therapeutic Index ◽  
Chemotherapeutic Agents ◽  
Potential Candidate ◽  
Anti Cancer

Abstract Background Therapeutic resistance to radiation and chemotherapy is one of the major obstacles in cancer treatment. Although synthetic radiosensitizers are pragmatic solution to enhance tumor sensitivity, they pose concerns of toxicity and non-specificity. In the last decades, scientists scrutinized novel plant-derived radiosensitizers and chemosensitizers, such as flavones, owing to their substantial physiological effects like low toxicity and non-mutagenic properties on the human cells. The combination therapy with apigenin is potential candidate in cancer therapeutics. This review explicates the combinatorial strategies involving apigenin to overcome drug resistance and boost the anti-cancer properties. Methods We selected full-text English papers on international databases like PubMed, Web of Science, Google Scholar, Scopus, and ScienceDirect from 1972 up to 2020. The keywords included in the search were: Apigenin, Chemoprotective, Chemosensitizing, Side Effects, and Molecular Mechanisms. Results In this review, we focused on combination therapy, particularly with apigenin augmenting the anti-cancer effects of chemo drugs on tumor cells, reduce their side effects, subdue drug resistance, and protect healthy cells. The reviewed research data implies that these co-therapies exhibited a synergistic effect on various cancer cells, where apigenin sensitized the chemo drug through different pathways including a significant reduction in overexpressed genes, AKT phosphorylation, NFκB, inhibition of Nrf2, overexpression of caspases, up-regulation of p53 and MAPK, compared to the monotherapies. Meanwhile, contrary to the chemo drugs alone, combined treatments significantly induced apoptosis in the treated cells. Conclusion Briefly, our analysis proposed that the combination therapies with apigenin could suppress the unwanted toxicity of chemotherapeutic agents. It is believed that these expedient results may pave the path for the development of drugs with a high therapeutic index. Nevertheless, human clinical trials are a prerequisite to consider the potential use of apigenin in the prevention and treatment of various cancers. Conclusively, the clinical trials to comprehend the role of apigenin as a chemoprotective agent are still in infancy. Graphical Abstract

scholarly journals Two Targets, One Hit: new Anticancer Therapeutics to Prevent Tumorigenesis Without Cardiotoxicity

2021 ◽  
Vol 11 ◽  
Author(s):  
Zoltán Szabó ◽  
Lilla Hornyák ◽  
Márton Miskei ◽  
Lóránt Székvölgyi
Keyword(s):  
Adverse Effect ◽  
Cell Proliferation ◽  
Antineoplastic Agents ◽  
Cancer Therapeutics ◽  
Therapeutic Interventions ◽  
Cancer Therapies ◽  
Cancer Cell Proliferation ◽  
Cardiovascular Toxicity ◽  
Allosteric Inhibitors ◽  
Anti Cancer

A serious adverse effect of cancer therapies is cardiovascular toxicity, which significantly limits the widespread use of antineoplastic agents. The promising new field of cardio-oncology offers the identification of potent anti-cancer therapeutics that effectively inhibit cancer cell proliferation without causing cardiotoxicity. Future introduction of recently identified cardio-safe compounds into clinical practice (including ERK dimerization inhibitors or BAX allosteric inhibitors) is expected to help oncologists avoid unwanted cardiological complications associated with therapeutic interventions.

scholarly journals Reversible renal-limited thrombotic microangiopathy due to gemcitabine-dexamethasone-cisplatin therapy: a case report

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Masashi Nishikubo ◽  
Yoshimitsu Shimomura ◽  
Nobuhiro Hiramoto ◽  
Naohiko Sawamura ◽  
Takako Yamaguchi ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Thrombotic Microangiopathy ◽  
Systemic Disease ◽  
Calcineurin Inhibitors ◽  
Chemotherapeutic Agents ◽  
Combination Drug ◽  
Drug Induced ◽  
Classical Triad ◽  
Cisplatin Therapy ◽  
Gemcitabine And Cisplatin

Abstract Background Gemcitabine and cisplatin are chemotherapeutic agents used for treating multiple cancers, and these agents are sometimes used in combination. Drug-induced thrombotic microangiopathy (TMA) is a rare but potentially fatal complication. It typically presents as a systemic disease with the classical triad of hemolytic anemia, thrombocytopenia, and organ damage. In contrast to systemic TMA, cases of renal-limited TMA, defined as biopsy-proven renal TMA without the classical triad, have been reported with relatively good prognosis. Most cases of renal-limited TMA are associated with calcineurin inhibitors, and cases of drug-induced renal-limited TMA due to gemcitabine-dexamethasone-cisplatin therapy have been rarely reported. Case presentation A 43-year-old woman with lymphoma developed acute kidney injury with marked proteinuria, microhematuria, and abnormal urinary casts after receiving one cycle of gemcitabine-dexamethasone-cisplatin therapy. Although she did not show hemolytic anemia and thrombocytopenia, renal biopsy showed diffuse injury to the glomerular endothelial cells, supporting the diagnosis of renal-limited TMA. Her condition improved only with the cessation of gemcitabine and cisplatin treatment. She received another chemotherapy without gemcitabine and platinum agents, and no recurrence of renal-limited TMA was observed. Conclusions Drug-induced TMA occurs early after gemcitabine and cisplatin use in renal-limited form and is reversible when detected and managed in a timely manner. Urinalysis, which is simple and inexpensive and can be easily performed, is a beneficial screening tool for early-onset drug-induced TMA among patients who receive gemcitabine-dexamethasone-cisplatin therapy.

scholarly journals Doxorubicin hydrochloride liposome and albumin-bound paclitaxel in cancer: a nanotechnology perspective

2021 ◽  
pp. 59-65
Author(s):  
Rajib Hossain ◽  
Rasel Ahmed Khan ◽  
Muhammad Torequl Islam ◽  
Divya Jain ◽  
Pracheta Janmeda ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Active Sites ◽  
Biosynthetic Pathway ◽  
Chemotherapeutic Agents ◽  
Cancer Therapies ◽  
Tumor Cell Membrane ◽  
Routes Of Administration ◽  
Anti Cancer ◽  
Specific Reactions ◽  
Cancerous Cells

Nanoparticles (1-100 nanometres in size), products of nanotechnology, offer a modern way to transport anti-cancer drugs by acting as transporters of drugs into tumor cells, hence quenching tumor cell proliferation. Such nanoparticles may be formulated to bind to the tumor cell membrane or inhibit specific reactions of tumor biosynthetic pathway by gene repression, or directly bind to the active sites of essential enzymes in the biosynthetic pathway. Consequently, drugs are completely delivered to the desired cancerous cells without system interference. Liposomal doxorubicin and albumin-bound paclitaxel are two examples of nanotechnologically developed drugs for treating cancer. Modern knowledge of nanotechnology opens up new opportunities for innovative research on cancer therapies and administration and helps minimize harm to healthy cells. This review focuses on the doses and routes of administration of these chemotherapeutic agents used in treating cancers.

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