scholarly journals Engineering Nanoplatform for Combined Cancer Therapeutics via Complementary Autophagy Inhibition

2022 ◽  
Vol 23 (2) ◽  
pp. 657
Author(s):  
Xuan Wang ◽  
Yunhao Li ◽  
Jianqing Lu ◽  
Xiongwei Deng ◽  
Yan Wu
Keyword(s):  
Cancer Therapeutics ◽  
Current Treatment ◽  
Cancer Therapies ◽  
Alternative Source ◽  
Anti Cancer ◽  
Treatment Paradigm ◽  
Potential Strategy ◽  
Turn Over ◽  
Druggable Targets ◽  
Autophagy Inhibition

Despite advances in the development of tumor treatments, mortality from cancer continues to increase. Nanotechnology is expected to provide an innovative anti-cancer therapy, to combat challenges such as multidrug resistance and tumor recurrence. Nevertheless, tumors can greatly rely on autophagy as an alternative source for metabolites, and which desensitizes cancer cells to therapeutic stress, hindering the success of any current treatment paradigm. Autophagy is a conserved process by which cells turn over their own constituents to maintain cellular homeostasis. The multistep autophagic pathway provides potentially druggable targets to inhibit pro-survival autophagy under various therapeutic stimuli. In this review, we focus on autophagy inhibition based on functional nanoplatforms, which may be a potential strategy to increase therapeutic sensitivity in combinational cancer therapies, including chemotherapy, radiotherapy, phototherapy, sonodynamic therapy, and immunotherapy.

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 Microbes as Medicines: Harnessing the Power of Bacteria in Advancing Cancer Treatment

2020 ◽  
Vol 21 (20) ◽  
pp. 7575 ◽  
Author(s):  
Shruti S. Sawant ◽  
Suyash M. Patil ◽  
Vivek Gupta ◽  
Nitesh K. Kunda
Keyword(s):  
Cancer Therapy ◽  
Cancer Treatment ◽  
Treatment Options ◽  
Current Treatment ◽  
Genetically Engineered ◽  
Cancer Therapies ◽  
Anti Cancer ◽  
Tumor Environment ◽  
Systemic Side Effects ◽  
Hypoxic Tumor

Conventional anti-cancer therapy involves the use of chemical chemotherapeutics and radiation and are often non-specific in action. The development of drug resistance and the inability of the drug to penetrate the tumor cells has been a major pitfall in current treatment. This has led to the investigation of alternative anti-tumor therapeutics possessing greater specificity and efficacy. There is a significant interest in exploring the use of microbes as potential anti-cancer medicines. The inherent tropism of the bacteria for hypoxic tumor environment and its ability to be genetically engineered as a vector for gene and drug therapy has led to the development of bacteria as a potential weapon against cancer. In this review, we will introduce bacterial anti-cancer therapy with an emphasis on the various mechanisms involved in tumor targeting and tumor suppression. The bacteriotherapy approaches in conjunction with the conventional cancer therapy can be effective in designing novel cancer therapies. We focus on the current progress achieved in bacterial cancer therapies that show potential in advancing existing cancer treatment options and help attain positive clinical outcomes with minimal systemic side-effects.

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 Hypoxia-Inducible Factors as an Alternative Source of Treatment Strategy for Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Musbau Adewumi Akanji ◽  
Damilare Rotimi ◽  
Oluyomi Stephen Adeyemi
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Critical Role ◽  
Treatment Strategies ◽  
Cancer Therapeutics ◽  
Cancer Therapies ◽  
Hypoxia Inducible Factors ◽  
Low Oxygen ◽  
Alternative Source ◽  
Patient Prognosis

Hypoxia-inducible factors (HIFs) are transcription factors that activate the transcription of genes necessary to circumvent to hypoxic (low oxygen level) environments. In carcinogenesis, HIFs play a critical role. Indeed, HIF-1α has been validated as a promising target for novel cancer therapeutics, even as clinical investigations have linked increased levels of HIF-1α with aggressive cancer progression as well as poor patient prognosis. More so, inhibiting HIF-1 activity restricted cancer progression. Therefore, HIF-1 is a viable target for cancer therapy. This may be expected considering the fact that cancer cells are known to be hypoxic. In order to survive the hypoxic microenvironment, cancer cells activate several biochemical pathways via the HIF-1α. Additionally, cellular and molecular insights have proved prospects of the HIF-1α pathway for the development of novel anticancer treatment strategies. The biochemical importance of hypoxia-inducible factors (HIFs) cannot be overemphasized as carcinogenesis, cancer progression, and HIFs are intricately linked. Therefore, this review highlights the significance of these linkages and also the prospects of HIFs as an alternative source of cancer therapies.

scholarly journals Oligonucleotides and microRNAs Targeting Telomerase Subunits in Cancer Therapy

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2337
Author(s):  
Adam Eckburg ◽  
Joshua Dein ◽  
Joseph Berei ◽  
Zachary Schrank ◽  
Neelu Puri
Keyword(s):  
Cancer Therapeutics ◽  
Telomerase Activity ◽  
Cancer Therapies ◽  
Human Telomerase Reverse Transcriptase ◽  
Conceptual Foundation ◽  
Telomerase Inhibitors ◽  
Current State ◽  
Anti Cancer ◽  
Cancer Types ◽  
Human Telomerase

Telomerase provides cancer cells with replicative immortality, and its overexpression serves as a near-universal marker of cancer. Anti-cancer therapeutics targeting telomerase have garnered interest as possible alternatives to chemotherapy and radiotherapy. Oligonucleotide-based therapies that inhibit telomerase through direct or indirect modulation of its subunits, human telomerase reverse transcriptase (hTERT) and human telomerase RNA gene (hTERC), are a unique and diverse subclass of telomerase inhibitors which hold clinical promise. MicroRNAs that play a role in the upregulation or downregulation of hTERT and respective progression or attenuation of cancer development have been effectively targeted to reduce telomerase activity in various cancer types. Tumor suppressor miRNAs, such as miRNA-512-5p, miRNA-138, and miRNA-128, and oncogenic miRNAs, such as miRNA-19b, miRNA-346, and miRNA-21, have displayed preclinical promise as potential hTERT-based therapeutic targets. Antisense oligonucleotides like GRN163L and T-oligos have also been shown to uniquely target the telomerase subunits and have become popular in the design of novel cancer therapies. Finally, studies suggest that G-quadruplex stabilizers, such as Telomestatin, preserve telomeric oligonucleotide architecture, thus inhibiting hTERC binding to the telomere. This review aims to provide an adept understanding of the conceptual foundation and current state of therapeutics utilizing oligonucleotides to target the telomerase subunits, including the advantages and drawbacks of each of these approaches.

scholarly journals The RARγ Oncogene: An Achilles Heel for Some Cancers

2021 ◽  
Vol 22 (7) ◽  
pp. 3632
Author(s):  
Geoffrey Brown ◽  
Kevin Petrie
Keyword(s):  
Stem Cells ◽  
Metastatic Disease ◽  
Retinoic Acid Receptor ◽  
Cancer Therapies ◽  
Anti Cancer ◽  
Dividing Cells ◽  
Bona Fide ◽  
Potential Strategy ◽  
Related Mortality

Cancer “stem cells” (CSCs) sustain the hierarchies of dividing cells that characterize cancer. The main causes of cancer-related mortality are metastatic disease and relapse, both of which originate primarily from CSCs, so their eradication may provide a bona fide curative strategy, though there maybe also the need to kill the bulk cancer cells. While classic anti-cancer chemotherapy is effective against the dividing progeny of CSCs, non-dividing or quiescent CSCs are often spared. Improved anti-cancer therapies therefore require approaches that target non-dividing CSCs, which must be underpinned by a better understanding of factors that permit these cells to maintain a stem cell-like state. During hematopoiesis, retinoic acid receptor (RAR) γ is selectively expressed by stem cells and their immediate progeny. It is overexpressed in, and is an oncogene for, many cancers including colorectal, renal and hepatocellular carcinoma, cholangiocarcinomas and some cases of acute myeloid leukemia that harbor RARγ fusion proteins. In vitro studies suggest that RARγ-selective and pan-RAR antagonists provoke the death of CSCs by necroptosis and point to antagonism of RARγ as a potential strategy to treat metastatic disease and relapse, and perhaps provide a cure for some cancers.

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.

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