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.

Variations in patient-reported outcome (PRO) collection and reporting in novel FDA approved anticancer therapies.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18202-e18202
Author(s):  
Surbhi Singhal ◽  
Evan Thomas Hall ◽  
Brooke Peterson Gabster ◽  
James Dickerson ◽  
Lidia Schapira
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Cancer Treatment ◽  
Treatment Options ◽  
Patient Reported Outcome ◽  
Cancer Therapies ◽  
Clinical Trial Registry ◽  
Fda Approval ◽  
Patient Reported ◽  
Anti Cancer

e18202 Background: Patient-reported outcomes (PROs) are increasingly valued as a key tool in patient-focused treatment decisions. However, a lack of standardization leads to significant variability in PRO collection and reporting in ground-breaking clinical trials of novel agents. We sought to characterize the mechanisms of assessment and variability by which PROs are reported for newly approved anti-cancer therapies. Methods: We reviewed the U.S. Food and Drug Administration (FDA) approvals between 2011 and 2017 for anti-cancer new molecular entities (NMEs) and new biologic approvals (BLAs). For each therapy, the pivotal clinical trial leading to FDA approval was identified using the national clinical trial (NCT) number and assessed for inclusion of PROs. A separate PubMed search was conducted to evaluate for PRO publication distinct from the original trial based on national clinical trial registry number. Results: From 2011 to 2017, the FDA approved 66 NMEs/BLAs based on 74 clinical trials for cancer treatment. Of the 74 clinical trial publications, 21 (28%) of the trials published PRO data in their original clinical publication, 18 (24%) published a separate PRO analysis, and 35 (47%) did not publish PRO data in either format. Among the 32 clinical trials (43%) that listed PROs as pre-specified outcomes, 72% published PROs (23/32). The separate PRO analyses (N = 18) were published considerably later following FDA approval (mean 605 days) than the original clinical trials (mean 20 days, N = 74, P < 0.001). Conclusions: As cancer treatment options expand, therapy decisions become increasingly nuanced. PROs assist decision-making by providing detailed information on important aspects of quality of life and tolerability. Our research has identified a significant lag in the publication of companion studies of PRO data associated with pivotal clinical trials, representing a meaningful gap in information critical to patients and oncologists in the process of making informed decisions.

scholarly journals MiR-144 overexpression as a promising therapeutic strategy to overcome glioblastoma cell invasiveness and resistance to chemotherapy

2019 ◽  
Vol 28 (16) ◽  
pp. 2738-2751 ◽  
Author(s):  
Ana M S Cardoso ◽  
Madalena Sousa ◽  
Catarina M Morais ◽  
Liliana R Oancea-Castillo ◽  
Anne Régnier-Vigouroux ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Cell Metabolism ◽  
Combined Therapy ◽  
Treatment Options ◽  
Primary Brain Tumor ◽  
Current Treatment ◽  
Cancer Therapies ◽  
Current Standard ◽  
Aberrant Expression ◽  
Post Surgery

Abstract Glioblastoma (GB) is the most aggressive and common form of primary brain tumor, characterized by fast proliferation, high invasion, and resistance to current standard treatment. The average survival rate post-diagnosis is only of 14.6 months, despite the aggressive standard post-surgery treatment approaches of radiotherapy concomitant with chemotherapy with temozolomide. Altered cell metabolism has been identified as an emerging cancer hallmark, including in GB, thus offering a new target for cancer therapies. On the other hand, abnormal expression levels of miRNAs, key regulators of multiple molecular pathways, have been correlated with pathological manifestations of cancer, such as chemoresistance, proliferation, and resistance to apoptosis. In this work, we hypothesized that gene therapy based on modulation of a miRNA with aberrant expression in GB and predicted to target crucial metabolic enzymes might impair tumor cell metabolism. We found that the increase of miR-144 levels, shown to be downregulated in U87 and DBTRG human GB cell lines, as well as in GB tumor samples, promoted the downregulation of mRNA of enzymes involved in bioenergetic pathways, with consequent alterations in cell metabolism, impairment of migratory capacity, and sensitization of DBTRG cells to a chemotherapeutic drug, the dichloroacetate (DCA). Taken together, our findings provide evidence that the miR-144 plus DCA combined therapy holds promise to overcome GB-acquired chemoresistance, therefore deserving to be explored toward its potential application as a complementary therapeutic approach to the current treatment options for this type of brain tumor.

scholarly journals Epigenetic Research in Stem Cell Bioengineering—Anti-Cancer Therapy, Regenerative and Reconstructive Medicine in Human Clinical Trials

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1016 ◽  
Author(s):  
Claudia Dompe ◽  
Krzysztof Janowicz ◽  
Greg Hutchings ◽  
Lisa Moncrieff ◽  
Maurycy Jankowski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trials ◽  
Stem Cell ◽  
Cancer Therapy ◽  
Regulation Of Gene Expression ◽  
Epigenetic Modifications ◽  
Transcriptional Level ◽  
Cancer Therapies ◽  
Stem Cell Engineering ◽  
Anti Cancer

The epigenome denotes all the information related to gene expression that is not contained in the DNA sequence but rather results from chemical changes to histones and DNA. Epigenetic modifications act in a cooperative way towards the regulation of gene expression, working at the transcriptional or post-transcriptional level, and play a key role in the determination of phenotypic variations in cells containing the same genotype. Epigenetic modifications are important considerations in relation to anti-cancer therapy and regenerative/reconstructive medicine. Moreover, a range of clinical trials have been performed, exploiting the potential of epigenetics in stem cell engineering towards application in disease treatments and diagnostics. Epigenetic studies will most likely be the basis of future cancer therapies, as epigenetic modifications play major roles in tumour formation, malignancy and metastasis. In fact, a large number of currently designed or tested clinical approaches, based on compounds regulating epigenetic pathways in various types of tumours, employ these mechanisms in stem cell bioengineering.

scholarly journals Targeting ERK-Hippo Interplay in Cancer Therapy

2020 ◽  
Vol 21 (9) ◽  
pp. 3236 ◽  
Author(s):  
Karel Vališ ◽  
Petr Novák
Keyword(s):  
Cancer Therapy ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Cross Talk ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Cancer Therapies ◽  
Anti Cancer ◽  
Targeted Inhibition

Extracellular signal-regulated kinase (ERK) is a part of the mitogen-activated protein kinase (MAPK) signaling pathway which allows the transduction of various cellular signals to final effectors and regulation of elementary cellular processes. Deregulation of the MAPK signaling occurs under many pathological conditions including neurodegenerative disorders, metabolic syndromes and cancers. Targeted inhibition of individual kinases of the MAPK signaling pathway using synthetic compounds represents a promising way to effective anti-cancer therapy. Cross-talk of the MAPK signaling pathway with other proteins and signaling pathways have a crucial impact on clinical outcomes of targeted therapies and plays important role during development of drug resistance in cancers. We discuss cross-talk of the MAPK/ERK signaling pathway with other signaling pathways, in particular interplay with the Hippo/MST pathway. We demonstrate the mechanism of cell death induction shared between MAPK/ERK and Hippo/MST signaling pathways and discuss the potential of combination targeting of these pathways in the development of more effective anti-cancer therapies.

scholarly journals Polymeric Co-Delivery Systems in Cancer Treatment: An Overview on Component Drugs’ Dosage Ratio Effect

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1035 ◽  
Author(s):  
Jiayi Pan ◽  
Kobra Rostamizadeh ◽  
Nina Filipczak ◽  
Vladimir Torchilin
Keyword(s):  
Cancer Therapy ◽  
Cancer Treatment ◽  
Therapeutic Agent ◽  
Polymeric Nanoparticles ◽  
Therapeutic Agents ◽  
Delivery Systems ◽  
Individual Therapy ◽  
Multiple Factors ◽  
Therapeutic Outcomes ◽  
Anti Cancer

Multiple factors are involved in the development of cancers and their effects on survival rate. Many are related to chemo-resistance of tumor cells. Thus, treatment with a single therapeutic agent is often inadequate for successful cancer therapy. Ideally, combination therapy inhibits tumor growth through multiple pathways by enhancing the performance of each individual therapy, often resulting in a synergistic effect. Polymeric nanoparticles prepared from block co-polymers have been a popular platform for co-delivery of combinations of drugs associated with the multiple functional compartments within such nanoparticles. Various polymeric nanoparticles have been applied to achieve enhanced therapeutic efficacy in cancer therapy. However, reported drug ratios used in such systems often vary widely. Thus, the same combination of drugs may result in very different therapeutic outcomes. In this review, we investigated polymeric co-delivery systems used in cancer treatment and the drug combinations used in these systems for synergistic anti-cancer effect. Development of polymeric co-delivery systems for a maximized therapeutic effect requires a deeper understanding of the optimal ratio among therapeutic agents and the natural heterogenicity of tumors.

scholarly journals Combinatorial Therapeutic Approaches with Nanomaterial-Based Photodynamic Cancer Therapy

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 120
Author(s):  
Yang Hao ◽  
Chih Kit Chung ◽  
Zhenfeng Yu ◽  
Ruben V. Huis in ‘t Veld ◽  
Ferry A. Ossendorp ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Treatment Options ◽  
Great Promise ◽  
Cancer Therapies ◽  
Multiple Cancer ◽  
Primary Tumors ◽  
Minimal Invasiveness ◽  
Combination Strategies ◽  
Therapeutic Drugs ◽  
Local Cell

Photodynamic therapy (PDT), in which a light source is used in combination with a photosensitizer to induce local cell death, has shown great promise in therapeutically targeting primary tumors with negligible toxicity and minimal invasiveness. However, numerous studies have shown that noninvasive PDT alone is not sufficient to completely ablate tumors in deep tissues, due to its inherent shortcomings. Therefore, depending on the characteristics and type of tumor, PDT can be combined with surgery, radiotherapy, immunomodulators, chemotherapy, and/or targeted therapy, preferably in a patient-tailored manner. Nanoparticles are attractive delivery vehicles that can overcome the shortcomings of traditional photosensitizers, as well as enable the codelivery of multiple therapeutic drugs in a spatiotemporally controlled manner. Nanotechnology-based combination strategies have provided inspiration to improve the anticancer effects of PDT. Here, we briefly introduce the mechanism of PDT and summarize the photosensitizers that have been tested preclinically for various cancer types and clinically approved for cancer treatment. Moreover, we discuss the current challenges facing the combination of PDT and multiple cancer treatment options, and we highlight the opportunities of nanoparticle-based PDT in cancer therapies.

scholarly journals MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 29 ◽  
Author(s):  
Hyun Ah Seo ◽  
Sokviseth Moeng ◽  
Seokmin Sim ◽  
Hyo Jeong Kuh ◽  
Soo Young Choi ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Therapeutic Resistance ◽  
Cancer Therapies ◽  
Anti Cancer ◽  
Different Types ◽  
Therapeutic Responses

The susceptibility of cancer cells to different types of treatments can be restricted by intrinsic and acquired therapeutic resistance, leading to the failure of cancer regression and remission. To overcome this problem, a combination therapy has been proposed as a fundamental strategy to improve therapeutic responses; however, resistance is still unavoidable. MicroRNA (miRNAs) are associated with cancer therapeutic resistance. The modulation of dysregulated miRNA levels through miRNA-based therapy comprising a replacement or inhibition approach has been proposed to sensitize cancer cells to other anti-cancer therapies. The combination of miRNA-based therapy with other anti-cancer therapies (miRNA-based combinatorial cancer therapy) is attractive, due to the ability of miRNAs to target multiple genes associated with the signaling pathways controlling therapeutic resistance. In this article, we present an overview of recent findings on the role of therapeutic resistance-related miRNAs in different types of cancer. We review the feasibility of utilizing dysregulated miRNAs in cancer cells and extracellular vesicles as potential candidates for miRNA-based combinatorial cancer therapy. We also discuss innate properties of miRNAs that need to be considered for more effective combinatorial cancer therapy.

Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Adjuvant Cancer Therapy, to Complement Immune Checkpoint Therapy and Other Traditional Cancer Therapies, with Least Auto-immune Side Effects through Eco-balance of Human Microbiome

2018 ◽  
Vol 11 (6) ◽  
pp. 4295-4317
Author(s):  
Malireddy S Reddy
Keyword(s):  
Side Effects ◽  
Cancer Therapy ◽  
Adjuvant Therapy ◽  
Cancer Treatment ◽  
Nosocomial Infections ◽  
Immune Checkpoint ◽  
Great Promise ◽  
Cancer Therapies ◽  
Immunological Mechanisms ◽  
Probiotic Strains

This paper describes a novel serendipitous discovery to successfully treat cancer with improved efficiency emerged while using Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy (originally discovered to prevent or treat nosocomial infections) as an adjuvant therapy along with the immune checkpoint therapy and other conventional cancer therapies. This new discovery is named as “Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Adjuvant Cancer Therapy”. Cancer is rising as a global epidemic, currently killing over 9 million people every year. This figure is supposed to get up to 13 million by the year 2030.  The cancer epidemic is more prevalent in the Western countries than Eastern countries. The cost of treating cancer was $290 billion in the year 2010 and it is supposed to get up to $458 billion/year by the year 2030.  Recently checkpoint immune therapy is showing great promise as a treatment tool. Yet the global success in treating the cancer is only 20% or slightly higher, with all the advancements and discoveries.  A new paradigm shift in cancer treatment has been discovered as serendipitous discovery to enhance the efficiency of the existing cancer therapies significantly. This serendipitous discovery came as a surprise while running community based clinical trials using the novel discovery of Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy to prevent or cure the hospital acquired or nosocomial infections, which are affecting over six million people with severe mortality.  Several physicians have observed that Dr. Reddy’s Probiotic therapy given for prevention or control of nosocomial infections significantly helped the recovery of cancer patients who were also receiving standard cancer therapies.  This article outlines the mechanism by which Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy assist to cure cancer at a much faster pace, with the least side effects, when used as adjuvant therapy along with the immune checkpoint therapy, and other standard cancer therapies.  Details are presented how the PD-1 and CTLA-4 blockade therapy works to reduce cancer and also the possible scientific explanations why such an immune checkpoint therapy only works on limited cancer cases.  The effect of Multiple Mixed Strain Probiotics on establishing the immune tolerance through reduction of local or systemic inflammation is also outlined. The possible biological and immunological mechanisms of how Multiple Mixed Strain Probiotic Therapy significantly enhances the immune checkpoint therapy (PD-1 and CTLA-4 blockade) has been presented with explicit details. The details are also presented showing how Multiple Mixed Strain Adjuvant Therapy can minimize or significantly reduce the unpleasant side effects of the current conventional and immune checkpoint cancer therapies. Practical clinical and experimental data presented to show the significance of Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy, as an adjuvant therapy, along with the standard cancer therapies to improve the cancer treatment efficiencies by up to 60%. Evidence is presented to illustrate and point out that the current FDA regulations will allow the use of Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic (Therapy) as nutritional supplement, since the probiotic strains used are categorized as food grade and GRAS (Generally Regarded as Safe), as per the 21 Code of Federal Regulations of the Food and Drug Administration.  Details are presented with genus and species identification of individual probiotic strains used in the Multiple Mixed Strain Probiotic Therapy. Thus special and formal FDA approval is not required to use them as adjuvants to improve the efficiency of traditional cancer therapies. Finally the scientific reasoning is presented with evidence to illustrate the utmost urgency and necessity of using Dr. M.S. Reddy’s “Multiple Mixed Strain Probiotic Therapy” along with the immune checkpoint therapy and other traditional cancer therapies to protect the lives of millions of people dying with cancer annually.  

scholarly journals A Promising Biocompatible Platform: Lipid-Based and Bio-Inspired Smart Drug Delivery Systems for Cancer Therapy

2018 ◽  
Vol 19 (12) ◽  
pp. 3859 ◽  
Author(s):  
Min Kim ◽  
Seung-Hae Kwon ◽  
Jung Choi ◽  
Aeju Lee
Keyword(s):  
Drug Delivery ◽  
Cancer Therapy ◽  
Drug Delivery Systems ◽  
Controlled Drug Release ◽  
Research Area ◽  
Delivery Systems ◽  
Cancer Therapies ◽  
Smart Systems ◽  
Tumor Microenvironments ◽  
Anti Cancer

Designing new drug delivery systems (DDSs) for safer cancer therapy during pre-clinical and clinical applications still constitutes a considerable challenge, despite advances made in related fields. Lipid-based drug delivery systems (LBDDSs) have emerged as biocompatible candidates that overcome many biological obstacles. In particular, a combination of the merits of lipid carriers and functional polymers has maximized drug delivery efficiency. Functionalization of LBDDSs enables the accumulation of anti-cancer drugs at target destinations, which means they are more effective at controlled drug release in tumor microenvironments (TMEs). This review highlights the various types of ligands used to achieve tumor-specific delivery and discusses the strategies used to achieve the effective release of drugs in TMEs and not into healthy tissues. Moreover, innovative recent designs of LBDDSs are also described. These smart systems offer great potential for more advanced cancer therapies that address the challenges posed in this research area.

scholarly journals Photodynamic Therapy and Hyperthermia in Combination Treatment—Neglected Forces in the Fight against Cancer

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1147
Author(s):  
Aleksandra Bienia ◽  
Olga Wiecheć-Cudak ◽  
Aleksandra Anna Murzyn ◽  
Martyna Krzykawska-Serda
Keyword(s):  
Photodynamic Therapy ◽  
Combination Therapy ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Combination Treatment ◽  
Therapeutic Agent ◽  
Diagnostic Methods ◽  
Cancer Therapies ◽  
Treatment Side Effects ◽  
Anti Cancer

Cancer is one of the leading causes of death in humans. Despite the progress in cancer treatment, and an increase in the effectiveness of diagnostic methods, cancer is still highly lethal and very difficult to treat in many cases. Combination therapy, in the context of cancer treatment, seems to be a promising option that may allow minimizing treatment side effects and may have a significant impact on the cure. It may also increase the effectiveness of anti-cancer therapies. Moreover, combination treatment can significantly increase delivery of drugs to cancerous tissues. Photodynamic therapy and hyperthermia seem to be ideal examples that prove the effectiveness of combination therapy. These two kinds of therapy can kill cancer cells through different mechanisms and activate various signaling pathways. Both PDT and hyperthermia play significant roles in the perfusion of a tumor and the network of blood vessels wrapped around it. The main goal of combination therapy is to combine separate mechanisms of action that will make cancer cells more sensitive to a given therapeutic agent. Such an approach in treatment may contribute toward increasing its effectiveness, optimizing the cancer treatment process in the future.

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