Research Techniques Made Simple: Preclinical Development of Combination Antitumor Targeted Therapies in Dermatology.

The Journal of Investigative Dermatology
Sara YumeenMichael Girardi

Abstract

The identification and application of targeted therapies that inhibit critical pathways in malignant cells have shown tremendous promise for improving clinical outcomes for patients with advanced cutaneous malignancies. However, tumor cell heterogeneity, development of drug resistance, and risks of off-target effects remain barriers to prolonged remission and definitive cure. Herein, we describe the potential that combinations of antitumor targeted agents may offer in overcoming these challenges and detail techniques whereby promising combination regimens can be identified and further evaluated preclinically. Cancer cell lines and primary patient-derived malignant cells can be utilized to perform dose-response screenings in vitro for individual targeted agents before moving toward the evaluation of potential synergistic combinations. Mathematical analyses, including the Chou-Talalay method, determine combination indices and Hill slopes that permit relative comparisons among various drug combinations by quantification of synergistic activities. Further preclinical in vivo evaluation of promising single versus combination regimens may be studied in relevant mouse models of cutaneous malignancy. Ultimately, the formulation of comb...Continue Reading

References

Nov 28, 2012·Cancer Metastasis Reviews·Michael D GoberJohn T Seykora
Feb 26, 2013·Journal of the National Cancer Institute·Jean-Pierre GilletMichael M Gottesman
Feb 5, 2014·Journal of Biomolecular Screening·Wei ZhaoHarry Yang
Mar 13, 2014·The Journal of Investigative Dermatology·Monique E VerhaegenAndrzej A Dlugosz
Nov 17, 2015·The Journal of Investigative Dermatology·Russell L GriffinSherrie J Divito
Jan 12, 2016·Therapeutic Advances in Medical Oncology·Zeynep Eroglu, Antoni Ribas
Sep 12, 2017·The New England Journal of Medicine·Georgina V LongJohn M Kirkwood
Oct 28, 2019·The Journal of Investigative Dermatology·Mark BellAndrew Woodland
Nov 13, 2019·Nature Reviews. Drug Discovery·Alan HuangBarbara Weber

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Annals of the New York Academy of Sciences
Shannon Decker, Edward A Sausville
Expert Opinion on Drug Discovery
Nicholas C NicolaidesLuigi Grasso
© 2021 Meta ULC. All rights reserved