Role of Biomarkers in Clinical Development of Cancer Therapies

2013 ◽  
pp. 59-75
Author(s):  
Helen Chen
Keyword(s):  
Clinical Development ◽  
Cancer Therapies

Potential of Mesenchymal Stem Cells in Anti-Cancer Therapies

2020 ◽  
Vol 15 (6) ◽  
pp. 482-491 ◽  
Author(s):  
Milena Kostadinova ◽  
Milena Mourdjeva
Keyword(s):  
Cancer Cells ◽  
Small Population ◽  
Tumor Formation ◽  
Bioactive Molecules ◽  
Cancer Therapies ◽  
New Methods ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Blocking Mechanisms

Mesenchymal stem/stromal cells (MSCs) are localized throughout the adult body as a small population in the stroma of the tissue concerned. In injury, tissue damage, or tumor formation, they are activated and leave their niche to migrate to the site of injury, where they release a plethora of growth factors, cytokines, and other bioactive molecules. With the accumulation of data about the interaction between MSCs and tumor cells, the dualistic role of MSCs remains unclear. However, a large number of studies have demonstrated the natural anti-tumor properties inherent in MSCs, so this is the basis for intensive research for new methods using MSCs as a tool to suppress cancer cell development. This review focuses specifically on advanced approaches in modifying MSCs to become a powerful, precision- targeted tool for killing cancer cells, but not normal healthy cells. Suppression of tumor growth by MSCs can be accomplished by inducing apoptosis or cell cycle arrest, suppressing tumor angiogenesis, or blocking mechanisms mediating metastasis. In addition, the chemosensitivity of cancer cells may be increased so that the dose of the chemotherapeutic agent used could be significantly reduced.

scholarly journals Roles of pRB in the Regulation of Nucleosome and Chromatin Structures

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Chiharu Uchida
Keyword(s):  
Target Genes ◽  
Chromosome Instability ◽  
Cancer Therapies ◽  
Induce Cell Cycle Arrest ◽  
Cellular Events ◽  
Cycle Arrest ◽  
Histone Modifiers ◽  
Physical Interactions ◽  
Functional Inactivation

Retinoblastoma protein (pRB) interacts with E2F and other protein factors to play a pivotal role in regulating the expression of target genes that induce cell cycle arrest, apoptosis, and differentiation. pRB controls the local promoter activity and has the ability to change the structure of nucleosomes and/or chromosomes via histone modification, epigenetic changes, chromatin remodeling, and chromosome organization. Functional inactivation of pRB perturbs these cellular events and causes dysregulated cell growth and chromosome instability, which are hallmarks of cancer cells. The role of pRB in regulation of nucleosome/chromatin structures has been shown to link to tumor suppression. This review focuses on the ability of pRB to control nucleosome/chromatin structures via physical interactions with histone modifiers and chromatin factors and describes cancer therapies based on targeting these protein factors.

scholarly journals Update on the role of pembrolizumab in patients with unresectable or metastatic colorectal cancer

2021 ◽  
Vol 14 ◽  
pp. 175628482110244
Author(s):  
Vanessa Wookey ◽  
Axel Grothey
Keyword(s):  
Colorectal Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Standard Of Care ◽  
Cancer Type ◽  
Cancer Therapies ◽  
Multiple Cancer ◽  
Multiple Treatment

Colorectal cancer (CRC) is the third most common cancer type in both men and women in the USA. Most patients with CRC are diagnosed as local or regional disease. However, the survival rate for those diagnosed with metastatic disease remains disappointing, despite multiple treatment options. Cancer therapies for patients with unresectable or metastatic CRC are increasingly being driven by particular biomarkers. The development of various immune checkpoint inhibitors has revolutionized cancer therapy over the last decade by harnessing the immune system in the treatment of cancer, and the role of immunotherapy continues to expand and evolve. Pembrolizumab is an anti-programmed cell death protein 1 immune checkpoint inhibitor and has become an essential part of the standard of care in the treatment regimens for multiple cancer types. This paper reviews the increasing evidence supporting and defining the role of pembrolizumab in the treatment of patients with unresectable or metastatic CRC.

scholarly journals Targeting macrophages in cancer immunotherapy

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zhaojun Duan ◽  
Yunping Luo
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Therapeutic Strategies ◽  
Cellular Immunotherapy ◽  
Cancer Therapies ◽  
Tumor Vaccines ◽  
Development And Differentiation ◽  
Promising Treatment ◽  
Cancer Immunotherapies

AbstractImmunotherapy is regarded as the most promising treatment for cancers. Various cancer immunotherapies, including adoptive cellular immunotherapy, tumor vaccines, antibodies, immune checkpoint inhibitors, and small-molecule inhibitors, have achieved certain successes. In this review, we summarize the role of macrophages in current immunotherapies and the advantages of targeting macrophages. To better understand and make better use of this type of cell, their development and differentiation characteristics, categories, typical markers, and functions were collated at the beginning of the review. Therapeutic strategies based on or combined with macrophages have the potential to improve the treatment efficacy of cancer therapies.

scholarly journals PARP Power: A Structural Perspective on PARP1, PARP2, and PARP3 in DNA Damage Repair and Nucleosome Remodelling

2021 ◽  
Vol 22 (10) ◽  
pp. 5112
Author(s):  
Lotte van Beek ◽  
Éilís McClay ◽  
Saleha Patel ◽  
Marianne Schimpl ◽  
Laura Spagnolo ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Binding ◽  
Parp Inhibitors ◽  
Covalent Modification ◽  
Activation Mechanism ◽  
Cancer Therapies ◽  
Damage Repair ◽  
Complementary Role ◽  
Functional Understanding

Poly (ADP-ribose) polymerases (PARP) 1-3 are well-known multi-domain enzymes, catalysing the covalent modification of proteins, DNA, and themselves. They attach mono- or poly-ADP-ribose to targets using NAD+ as a substrate. Poly-ADP-ribosylation (PARylation) is central to the important functions of PARP enzymes in the DNA damage response and nucleosome remodelling. Activation of PARP happens through DNA binding via zinc fingers and/or the WGR domain. Modulation of their activity using PARP inhibitors occupying the NAD+ binding site has proven successful in cancer therapies. For decades, studies set out to elucidate their full-length molecular structure and activation mechanism. In the last five years, significant advances have progressed the structural and functional understanding of PARP1-3, such as understanding allosteric activation via inter-domain contacts, how PARP senses damaged DNA in the crowded nucleus, and the complementary role of histone PARylation factor 1 in modulating the active site of PARP. Here, we review these advances together with the versatility of PARP domains involved in DNA binding, the targets and shape of PARylation and the role of PARPs in nucleosome remodelling.

scholarly journals WEE1 Inhibitor: Clinical Development

2021 ◽  
Vol 23 (9) ◽  
Author(s):  
Anthony Kong ◽  
Hisham Mehanna
Keyword(s):  
Clinical Trials ◽  
Tp53 Mutation ◽  
Predictive Biomarker ◽  
Concurrent Chemotherapy ◽  
Clinical Development ◽  
Novel Agents ◽  
The Novel ◽  
Grade 3 ◽  
Chemotherapy Agents

Abstract Purpose of Review WEE1 inhibitor has been shown to potential chemotherapy or radiotherapy sensitivity in preclinical models, particularly in p53-mutated or deficient cancer cells although not exclusively. Here, we review the clinical development of WEE1 inhibitor in combination with chemotherapy or radiotherapy with concurrent chemotherapy as well as its combination with different novel agents. Recent Findings Although several clinical trials have shown that WEE1 inhibitor can be safely combined with different chemotherapy agents as well as radiotherapy with concurrent chemotherapy, its clinical development has been hampered by the higher rate of grade 3 toxicities when added to standard treatments. A few clinical trials had also been conducted to test WEE1 inhibitor using TP53 mutation as a predictive biomarker. However, TP53 mutation has not been shown to be the most reliable predictive biomarker and the benefit of adding WEE1 inhibitor to chemotherapy has been modest, even in TP53 biomarker-driven studies. Summary There are ongoing clinical trials testing WEE1 inhibitor with novel agents such as ATR and PAPR inhibitors as well as anti-PDL1 immunotherapy, which may better define the role of WEE1 inhibitor in the future if any of the novel treatment combination will show superior anti-tumor efficacy with a good safety profile compared to monotherapy and/or standard treatment.

scholarly journals The Role of Herbal Bioactive Components in Mitochondria Function and Cancer Therapy

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Fangfang Tao ◽  
Yanrong Zhang ◽  
Zhiqian Zhang
Keyword(s):  
Cancer Therapy ◽  
Cancer Cell ◽  
Apoptotic Cell ◽  
Redox Status ◽  
Cancer Therapies ◽  
Bioactive Components ◽  
Atp Production

Mitochondria are highly dynamic double-membrane organelles which play a well-recognized role in ATP production, calcium homeostasis, oxidation-reduction (redox) status, apoptotic cell death, and inflammation. Dysfunction of mitochondria has long been observed in a number of human diseases, including cancer. Targeting mitochondria metabolism in tumors as a cancer therapeutic strategy has attracted much attention for researchers in recent years due to the essential role of mitochondria in cancer cell growth, apoptosis, and progression. On the other hand, a series of studies have indicated that traditional medicinal herbs, including traditional Chinese medicines (TCM), exert their potential anticancer effects as an effective adjunct treatment for alleviating the systemic side effects of conventional cancer therapies, for reducing the risk of recurrence and cancer mortality and for improving the quality of patients’ life. An amazing feature of these structurally diverse bioactive components is that majority of them target mitochondria to provoke cancer cell-specific death program. The aim of this review is to summarize the in vitro and in vivo studies about the role of these herbs, especially their bioactive compounds in the modulation of the disturbed mitochondrial function for cancer therapy.

scholarly journals Understanding the Redox Biology of Selenium in the Search of Targeted Cancer Therapies

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 420 ◽  
Author(s):  
Jeffrey M. Stolwijk ◽  
Rohan Garje ◽  
Jessica C. Sieren ◽  
Garry R. Buettner ◽  
Yousef Zakharia
Keyword(s):  
Selenium Deficiency ◽  
Vital Role ◽  
High Dose ◽  
Specific Cell ◽  
Cancer Therapies ◽  
Selenium Compounds ◽  
Redox Biology ◽  
Selenium Treatment ◽  
Prevention Of Cancer

Selenium (Se) is an essential trace nutrient required for optimal human health. It has long been suggested that selenium has anti-cancer properties. However, clinical trials have shown inconclusive results on the potential of Se to prevent cancer. The suggested role of Se in the prevention of cancer is centered around its role as an antioxidant. Recently, the potential of selenium as a drug rather than a supplement has been uncovered. Selenium compounds can generate reactive oxygen species that could enhance the treatment of cancer. Transformed cells have high oxidative distress. As normal cells have a greater capacity to meet oxidative challenges than tumor cells, increasing the flux of oxidants with high dose selenium treatment could result in cancer-specific cell killing. If the availability of Se is limited, supplementation of Se can increase the expression and activities of Se-dependent proteins and enzymes. In cell culture, selenium deficiency is often overlooked. We review the importance of achieving normal selenium biology and how Se deficiency can lead to adverse effects. We examine the vital role of selenium in the prevention and treatment of cancer. Finally, we examine the properties of Se-compounds to better understand how each can be used to address different research questions.

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