Bio-vehicles of cytotoxic drugs for delivery to tumor specific targets for cancer precision therapy

Background: The Human Genome Project has unleashed the power of genomics in clinical practice as a choice of individualized therapy, particularly in cancer treatment. Pharmacogenomics is an interdisciplinary field of genomics that deals with drug response, based on individual genetic makeup. Objective: The main genetic events associated with carcinogenesis activate oncogenes or inactivate tumor-suppressor genes. Therefore, drugs should be specific to inactivate or regulate these mutant genes and their protein products for effective cancer treatment. In this review, we summarize how polymedication decisions in cancer treatments based on the evaluation of cytochrome P450 (CYP450) polymorphisms are applied for pharmacogenetic assessment of anticancer therapy outcomes. Results: However, multiple genetic events linked, inactivating a single mutant gene product, may be insufficient to inhibit tumor progress. Thus, genomics and pharmacogenetics directly influence a patient’s response and aid in guiding clinicians to select the safest and most effective combination of medications for a cancer patient from the initial prescription. Conclusion: This review outlines the roles of oncogenes, the importance of cytochrome P450 (CYP450) in cancer susceptibility, and its impact on drug metabolism, proposing combined approaches to achieve precision therapy.

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Two drug combinations vs combinations of 3 or more cytotoxic drugs for metastatic breast cancer

10.1002/14651858.cd003369.pub2 ◽

2009 ◽

Author(s):

Davina Ghersi ◽

John Simes ◽

I Craig Henderson ◽

Russell Basser ◽

Christine Brunswick ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Metastatic Breast ◽

Drug Combinations ◽

Cytotoxic Drugs

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The Blockade of Tumoral IL1β-Mediated Signaling in Normal Colonic Fibroblasts Sensitizes Tumor Cells to Chemotherapy and Prevents Inflammatory CAF Activation

International Journal of Molecular Sciences ◽

10.3390/ijms22094960 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4960

Author(s):

Natalia Guillén Díaz-Maroto ◽

Gemma Garcia-Vicién ◽

Giovanna Polcaro ◽

María Bañuls ◽

Nerea Albert ◽

...

Keyword(s):

Cancer Cells ◽

Tumor Cells ◽

Cell Types ◽

Colorectal Tumor ◽

Cytotoxic Drugs ◽

Differential Sensitivity ◽

Paracrine Signaling ◽

Inflammatory Phenotype ◽

Heterotypic Interactions ◽

Carcinoma Associated Fibroblasts

Heterotypic interactions between newly transformed cells and normal surrounding cells define tumor’s fate in incipient carcinomas. Once homeostasis has been lost, normal resident fibroblasts become carcinoma-associated fibroblasts, conferring protumorogenic properties on these normal cells. Here we describe the IL1β-mediated interplay between cancer cells and normal colonic myofibroblasts (NCFs), which bestows differential sensitivity to cytotoxic drugs on tumor cells. We used NCFs, their conditioned media (CM), and cocultures with tumor cells to characterize the IL1β-mediated crosstalk between both cell types. We silenced IL1β in tumor cells to demonstrate that such cells do not exert an influence on NCFs inflammatory phenotype. Our results shows that IL1β is overexpressed in cocultured tumor cells. IL1β enables paracrine signaling in myofibroblasts, converting them into inflammatory-CAFs (iCAF). IL1β-stimulated-NCF-CM induces migration and differential sensitivity to oxaliplatin in colorectal tumor cells. Such chemoprotective effect has not been evidenced for TGFβ1-driven NCFs. IL1β induces the loss of a myofibroblastic phenotype in NCFs and acquisition of iCAF traits. In conclusion, IL1β-secreted by cancer cells modify surrounding normal fibroblasts to confer protumorogenic features on them, particularly tolerance to cytotoxic drugs. The use of IL1β-blocking agents might help to avoid the iCAF traits acquisition and consequently to counteract the protumorogenic actions these cells.

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Smart Nanoparticles for Chemo-Based Combinational Therapy

Pharmaceutics ◽

10.3390/pharmaceutics13060853 ◽

2021 ◽

Vol 13 (6) ◽

pp. 853

Author(s):

Binita Shrestha ◽

Lijun Wang ◽

Eric M. Brey ◽

Gabriela Romero Uribe ◽

Liang Tang

Keyword(s):

Cancer Treatment ◽

Cancer Biology ◽

Complex Disease ◽

Rapid Development ◽

Acquired Resistance ◽

Therapeutic Index ◽

Chemotherapeutic Agents ◽

Combinational Therapy ◽

Precision Therapy ◽

External Stimuli

Cancer is a heterogeneous and complex disease. Traditional cancer therapy is associated with low therapeutic index, acquired resistance, and various adverse effects. With the increasing understanding of cancer biology and technology advancements, more strategies have been exploited to optimize the therapeutic outcomes. The rapid development and application of nanomedicine have motivated this progress. Combinational regimen, for instance, has become an indispensable approach for effective cancer treatment, including the combination of chemotherapeutic agents, chemo-energy, chemo-gene, chemo-small molecules, and chemo-immunology. Additionally, smart nanoplatforms that respond to external stimuli (such as light, temperature, ultrasound, and magnetic field), and/or to internal stimuli (such as changes in pH, enzymes, hypoxia, and redox) have been extensively investigated to improve precision therapy. Smart nanoplatforms for combinational therapy have demonstrated the potential to be the next generation cancer treatment regimen. This review aims to highlight the recent advances in smart combinational therapy.

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Comprehensive Analysis of SFRP Family Members Prognostic Value and Immune Infiltration in Gastric Cancer

Life ◽

10.3390/life11060522 ◽

2021 ◽

Vol 11 (6) ◽

pp. 522

Author(s):

Dehua Liu ◽

Chenyu Sun ◽

Nahyun Kim ◽

Chandur Bhan ◽

John Pocholo Whitaker Tuason ◽

...

Keyword(s):

Gastric Cancer ◽

Wnt Signaling ◽

Signaling Pathway ◽

Prognostic Value ◽

Immune Cell ◽

System Development ◽

Wnt Signaling Pathway ◽

Immune System Development ◽

Precision Therapy ◽

Gastric Cancer Patients

Gastric cancer (GC) is the fifth most common cancer globally. Secreted frizzled-related proteins (SFRP) are important elements associated with the Wnt signaling pathway, and its dysregulated expression is found in multiple cancers. However, the function of distinct SFRPs in GC remains poorly understood. We investigated the differential expression, prognostic value, and immune cell infiltration of SFRPs in gastric cancer patients from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan–Meier plotter, cBioPortal, STRING, Gene-MANIA, DAVID, MethSurv, and TIMER databases. We found that the expression levels of SFRP2 and SFRP4 were significantly increased in GC tissues, whereas the SFRP1 and SFRP5 expressions were reduced. SFRP1, SFRP2, and SFRP5 were significantly correlated with the clinical cancer stage in GC patients. Higher expression of SFRPs was associated with short overall survival (OS) in GC patients. Besides, high SFRPs methylation showed favorable OS in GC patients. The functions of SFRPs were primarily related to the Wnt signaling pathway, immune system development, and basal cell carcinoma. The expression of SFRPs was strongly correlated with immune infiltrating cells, including CD4+ T cells and macrophages in GC. Our study indicated that SFRPs could be potential targets of precision therapy and prognostic biomarkers for the survival of GC patients.

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Physical Resilience as a Determinant of Healthspan and Lifespan in Mice

Innovation in Aging ◽

10.1093/geroni/igaa057.3031 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 829-829

Author(s):

Nathan LeBrasseur

Keyword(s):

Middle Ages ◽

Interest Group ◽

Later Life ◽

Cytotoxic Drugs ◽

Geriatric Syndromes ◽

Age Related ◽

Fundamental Biology ◽

Dynamic Measures ◽

Biology Of Aging ◽

Insight Into

Abstract Dynamic measures of physical resilience—the ability to resist and recover from a challenge—may be informative of biological age far prior to overt manifestations such as age-related diseases and geriatric syndromes (i.e., frailty). If true, physical resilience at younger or middle ages may be predictive of future healthspan and lifespan, and provide a unique paradigm in which interventions targeting the fundamental biology of aging can be tested. This seminar will discuss research on the development of clinically-relevant measures of physical resilience in mice, including anesthesia, surgery, and cytotoxic drugs. It will further highlight how these measures compare between young, middle-aged, and older mice, and how mid-life resilience relates to later-life healthspan. Finally, it will provide insight into whether interventions targeting the biology of aging can modify physical resilience in mice. Part of a symposium sponsored by Epidemiology of Aging Interest Group.

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Decision theory for precision therapy of breast cancer

Scientific Reports ◽

10.1038/s41598-021-82418-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Michael Kenn ◽

Dan Cacsire Castillo-Tong ◽

Christian F. Singer ◽

Rudolf Karch ◽

Michael Cibena ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Decision Theory ◽

Data Science ◽

Gene Expression Omnibus ◽

Hormone Receptor Status ◽

Breast Cancer Patients ◽

Receptor Status ◽

Kaplan Meier ◽

Precision Therapy

AbstractCorrectly estimating the hormone receptor status for estrogen (ER) and progesterone (PGR) is crucial for precision therapy of breast cancer. It is known that conventional diagnostics (immunohistochemistry, IHC) yields a significant rate of wrongly diagnosed receptor status. Here we demonstrate how Dempster Shafer decision Theory (DST) enhances diagnostic precision by adding information from gene expression. We downloaded data of 3753 breast cancer patients from Gene Expression Omnibus. Information from IHC and gene expression was fused according to DST, and the clinical criterion for receptor positivity was re-modelled along DST. Receptor status predicted according to DST was compared with conventional assessment via IHC and gene-expression, and deviations were flagged as questionable. The survival of questionable cases turned out significantly worse (Kaplan Meier p < 1%) than for patients with receptor status confirmed by DST, indicating a substantial enhancement of diagnostic precision via DST. This study is not only relevant for precision medicine but also paves the way for introducing decision theory into OMICS data science.

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Correction to: Precision Therapy for Brain Tumors in Hereditary Syndromes

Current Treatment Options in Oncology ◽

10.1007/s11864-021-00902-8 ◽

2021 ◽

Vol 22 (9) ◽

Author(s):

Gerald C. Wallace ◽

Madeleine Tjoelker ◽

Kaitlyn Bartley ◽

John W. Henson

Keyword(s):

Brain Tumors ◽

Hereditary Syndromes ◽

Precision Therapy

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