scholarly journals Development of Glypican-3 Targeting Immunotoxins for the Treatment of Liver Cancer: An Update

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 934
Author(s):  
Bryan D. Fleming ◽  
Mitchell Ho
Keyword(s):  
Liver Cancer ◽  
Half Life ◽  
Potential Role ◽  
Cancer Therapeutics ◽  
Bacterial Toxin ◽  
T Cell Epitopes ◽  
Cancer Treatments ◽  
Liver Cancers ◽  
Global Demand ◽  
High Immunogenicity

Hepatocellular carcinoma (HCC) accounts for most liver cancers and represents one of the deadliest cancers in the world. Despite the global demand for liver cancer treatments, there remain few options available. The U.S. Food and Drug Administration (FDA) recently approved Lumoxiti, a CD22-targeting immunotoxin, as a treatment for patients with hairy cell leukemia. This approval helps to demonstrate the potential role that immunotoxins can play in the cancer therapeutics pipeline. However, concerns have been raised about the use of immunotoxins, including their high immunogenicity and short half-life, in particular for treating solid tumors such as liver cancer. This review provides an overview of recent efforts to develop a glypican-3 (GPC3) targeting immunotoxin for treating HCC, including strategies to deimmunize immunotoxins by removing B- or T-cell epitopes on the bacterial toxin and to improve the serum half-life of immunotoxins by incorporating an albumin binding domain.

scholarly journals The role of the bacterial microbiome in the treatment of cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zi-Kun Yu ◽  
Rui-Ling Xie ◽  
Rui You ◽  
You-Ping Liu ◽  
Xu-Yin Chen ◽  
...  
Keyword(s):  
Potential Role ◽  
Human Microbiome ◽  
Cancer Therapeutics ◽  
Future Research ◽  
Host Immune System ◽  
Cancer Therapies ◽  
Cancer Treatments ◽  
Bacterial Microbiota ◽  
Bacterial Microbiome

AbstractThe human microbiome is defined as the microorganisms that reside in or on the human body, such as bacteria, viruses, fungi, and protozoa, and their genomes. The human microbiome participates in the modulation of human metabolism by influencing several intricate pathways. The association between specific bacteria or viruses and the efficacy of cancer treatments and the occurrence of treatment-related toxicity in cancer patients has been reported. However, the understanding of the interaction between the host microbiome and the cancer treatment response is limited, and the microbiome potentially plays a greater role in the treatment of cancer than reported to date. Here, we provide a thorough review of the potential role of the gut and locally resident bacterial microbiota in modulating responses to different cancer therapeutics to demonstrate the association between the gut or locally resident bacterial microbiota and cancer therapy. Probable mechanisms, such as metabolism, the immune response and the translocation of microbiome constituents, are discussed to promote future research into the association between the microbiome and other types of cancer. We conclude that the interaction between the host immune system and the microbiome may be the basis of the role of the microbiome in cancer therapies. Future research on the association between host immunity and the microbiome may improve the efficacy of several cancer treatments and provide insights into the cause of treatment-related side effects.

scholarly journals Tumor-Intrinsic Mechanisms Regulating Immune Exclusion in Liver Cancers

2021 ◽  
Vol 12 ◽  
Author(s):  
Katherine E. Lindblad ◽  
Marina Ruiz de Galarreta ◽  
Amaia Lujambio
Keyword(s):  
Liver Cancer ◽  
Rational Design ◽  
Immune Escape ◽  
Current Knowledge ◽  
Treatment Options ◽  
Health Concern ◽  
Patient Stratification ◽  
Tumor Immune Evasion ◽  
Advanced Hcc ◽  
Liver Cancers

Representing the fourth leading cause of cancer-related mortality worldwide, liver cancers constitute a major global health concern. Hepatocellular carcinoma (HCC), the most frequent type of liver cancer, is associated with dismal survival outcomes and has traditionally had few treatment options available. In fact, up until 2017, treatment options for advanced HCC were restricted to broad acting tyrosine kinase inhibitors, including Sorafenib, which has been the standard of care for over a decade. Since 2017, a multitude of mono- and combination immunotherapies that include pembrolizumab, nivolumab, ipilumumab, atezolizumab, and bevacizumab have been FDA-approved for the treatment of advanced HCC with unprecedented response rates ranging from 20 to 30% of patients. However, this also means that ~70% of patients do not respond to this treatment and currently very little is known regarding mechanisms of action of these immunotherapies as well as predictors of response to facilitate patient stratification. With the recent success of immunotherapies in HCC, there is a pressing need to understand mechanisms of tumor immune evasion and resistance to these immunotherapies in order to identify biomarkers of resistance or response. This will enable better patient stratification as well as the rational design of combination immunotherapies to restore sensitivity in resistant patients. The aim of this review is to summarize the current knowledge to date of tumor-intrinsic mechanisms of immune escape in liver cancer, specifically in the context of HCC.

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 Gene Therapy for Liver Cancers: Current Status from Basic to Clinics

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1865 ◽  
Author(s):  
Kenya Kamimura ◽  
Takeshi Yokoo ◽  
Hiroyuki Abe ◽  
Shuji Terai
Keyword(s):  
Gene Therapy ◽  
Liver Cancer ◽  
Liver Diseases ◽  
Malignant Tumors ◽  
Therapeutic Options ◽  
Endocrine Function ◽  
Current Status ◽  
Congenital Disease ◽  
Gene Therapies ◽  
Liver Cancers

The liver is a key organ for metabolism, protein synthesis, detoxification, and endocrine function, and among liver diseases, including hepatitis, cirrhosis, malignant tumors, and congenital disease, liver cancer is one of the leading causes of cancer-related deaths worldwide. Conventional therapeutic options such as embolization and chemotherapy are not effective against advanced-stage liver cancer; therefore, continuous efforts focus on the development of novel therapeutic options, including molecular targeted agents and gene therapy. In this review, we will summarize the progress toward the development of gene therapies for liver cancer, with an emphasis on recent clinical trials and preclinical studies.

scholarly journals Roles of Lysyl Oxidase Family Members in the Tumor Microenvironment and Progression of Liver Cancer

2020 ◽  
Vol 21 (24) ◽  
pp. 9751
Author(s):  
Hung-Yu Lin ◽  
Chia-Jung Li ◽  
Ya-Ling Yang ◽  
Ying-Hsien Huang ◽  
Ya-Tze Hsiau ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Liver Cancer ◽  
Lysyl Oxidase ◽  
Primary Liver Cancer ◽  
Target Therapy ◽  
Family Members ◽  
Clinical Value ◽  
Ecm Remodeling ◽  
Liver Cancers ◽  
Advanced Stages

The lysyl oxidase (LOX) family members are secreted copper-dependent amine oxidases, comprised of five paralogues: LOX and LOX-like l-4 (LOXL1-4), which are characterized by catalytic activity contributing to the remodeling of the cross-linking of the structural extracellular matrix (ECM). ECM remodeling plays a key role in the angiogenesis surrounding tumors, whereby a corrupt tumor microenvironment (TME) takes shape. Primary liver cancer includes hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), ranked as the seventh most common cancer globally, with limited therapeutic options for advanced stages. In recent years, a growing body of evidence has revealed the key roles of LOX family members in the pathogenesis of liver cancer and the shaping of TME, indicating their notable potential as therapeutic targets. We herein review the clinical value and novel biological roles of LOX family members in tumor progression and the TME of liver cancers. In addition, we highlight recent insights into their mechanisms and their potential involvement in the development of target therapy for liver cancer.

SU-FF-T-70: A Treatment Planning Study of Liver Cancer Treatments with a Flattening Filter Free Linear Accelerator

2006 ◽  
Vol 33 (6Part7) ◽  
pp. 2064-2065 ◽  
Author(s):  
O Vassiliev ◽  
A Beddar ◽  
S Krishnan ◽  
T Briere ◽  
M Gillin ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Treatment Planning ◽  
Linear Accelerator ◽  
Planning Study ◽  
Cancer Treatments ◽  
Flattening Filter Free ◽  
Flattening Filter

scholarly journals Predicting Clinical Efficacy of Vascular Disrupting Agents in Rodent Models of Primary and Secondary Liver Cancers: An Overview with Imaging-Histopathology Correlation

Diagnostics ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 78 ◽  
Author(s):  
Yewei Liu ◽  
Shuncong Wang ◽  
Xiaohui Zhao ◽  
Yuanbo Feng ◽  
Guy Bormans ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Liver Cancer ◽  
Human Liver ◽  
Cellular Differentiation ◽  
Liver Tumors ◽  
Pancreatic Tumors ◽  
Imaging Biomarkers ◽  
Vascular Disrupting Agents ◽  
Liver Cancers ◽  
Vascular Disrupting

Vascular disrupting agents (VDAs) have entered clinical trials for over 15 years. As the leading VDA, combretastatin A4 phosphate (CA4P) has been evaluated in combination with chemotherapy and molecular targeting agents among patients with ovarian cancer, lung cancer and thyroid cancer, but still remains rarely explored in human liver cancers. To overcome tumor residues and regrowth after CA4P monotherapy, a novel dual targeting pan-anticancer theragnostic strategy, i.e., OncoCiDia, has been developed and shown promise previously in secondary liver tumor models. Animal model of primary liver cancer is time consuming to induce, but of value for more closely mimicking human liver cancers in terms of tumor angiogenesis, histopathological heterogeneity, cellular differentiation, tumor components, cancer progression and therapeutic response. Being increasingly adopted in VDA researches, multiparametric magnetic resonance imaging (MRI) provides imaging biomarkers to reflect in vivo tumor responses to drugs. In this article as a chapter of a doctoral thesis, we overview the construction and clinical relevance of primary and secondary liver cancer models in rodents. Target selection for CA4P therapy assisted by enhanced MRI using hepatobiliary contrast agents (CAs), and therapeutic efficacy evaluated by using MRI with a non-specific contrast agent, dynamic contrast enhanced (DCE) imaging, diffusion weighted imaging (DWI) are also described. We then summarize diverse responses among primary hepatocellular carcinomas (HCCs), secondary liver and pancreatic tumors to CA4P, which appeared to be related to tumor size, vascularity, and cellular differentiation. In general, imaging-histopathology correlation studies allow to conclude that CA4P tends to be more effective in secondary liver tumors and in more differentiated HCCs, but less effective in less differentiated HCCs and implanted pancreatic tumor. Notably, cirrhotic liver may be responsive to CA4P as well. All these could be instructive for future clinical trials of VDAs.

scholarly journals Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2134 ◽  
Author(s):  
Lynda Wyld ◽  
Ilaria Bellantuono ◽  
Tamara Tchkonia ◽  
Jenna Morgan ◽  
Olivia Turner ◽  
...  
Keyword(s):  
Malignant Disease ◽  
Potential Role ◽  
Disease Recurrence ◽  
Bioactive Molecules ◽  
Cancer Therapies ◽  
Cancer Cell Proliferation ◽  
Cancer Treatments ◽  
Telomere Shortening ◽  
After Cancer ◽  
Active Investigation

Cellular senescence is a key component of human aging that can be induced by a range of stimuli, including DNA damage, cellular stress, telomere shortening, and the activation of oncogenes. Senescence is generally regarded as a tumour suppressive process, both by preventing cancer cell proliferation and suppressing malignant progression from pre-malignant to malignant disease. It may also be a key effector mechanism of many types of anticancer therapies, such as chemotherapy, radiotherapy, and endocrine therapies, both directly and via bioactive molecules released by senescent cells that may stimulate an immune response. However, senescence may contribute to reduced patient resilience to cancer therapies and may provide a pathway for disease recurrence after cancer therapy. A new group of drugs, senotherapies, (drugs which interact with senescent cells to interfere with their pro-aging impacts by either selectively destroying senescent cells (senolytic drugs) or inhibiting their function (senostatic drugs)) are under active investigation to determine whether they can enhance the efficacy of cancer therapies and improve resilience to cancer treatments. Senolytic drugs include quercetin, navitoclax, and fisetin and preclinical and early phase clinical data are emerging of their potential role in cancer treatments, although none are yet in routine use clinically. This article provides a review of these issues.

scholarly journals Revisiting the Concept of Stress in the Prognosis of Solid Tumors: A Role for Stress Granules Proteins?

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2470
Author(s):  
Anaïs Aulas ◽  
Pascal Finetti ◽  
Shawn M. Lyons ◽  
François Bertucci ◽  
Daniel Birnbaum ◽  
...  
Keyword(s):  
Stress Response ◽  
Patient Outcomes ◽  
Potential Role ◽  
Stress Granules ◽  
Cancer Treatments ◽  
Development Of Resistance ◽  
Therapeutic Drugs ◽  
Improve Patient ◽  
Survival Mechanisms

Cancer treatments are constantly evolving with new approaches to improve patient outcomes. Despite progresses, too many patients remain refractory to treatment due to either the development of resistance to therapeutic drugs and/or metastasis occurrence. Growing evidence suggests that these two barriers are due to transient survival mechanisms that are similar to those observed during stress response. We review the literature and current available open databases to study the potential role of stress response and, most particularly, the involvement of Stress Granules (proteins) in cancer. We propose that Stress Granule proteins may have prognostic value for patients.

Sign in / Sign up

Export Citation Format

Share Document