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Peripheral Blood Mononuclear Cells (PBMCs) in Cancer Drug Discovery and Development

Jan 30, 2014 3:00:06 PM / by Maria

In Part II of this series we discussed how peripheral blood mononuclear cells can be used to screen for drugs responses in healthy and infected cells. Here we discuss other measurements that are particularly useful in the context of cancer drug discovery and development.

Cancer is a complex disease and the effects of chemotherapeutics only add to the complexity in making decisions for patient treatment plans.  Unfortunately, the risk of being diagnosed with cancer at some point during your lifetime is estimated at 40.8% based on recent data.[1]  This is a problem too big to avoid that demands continued research in to disease and drug mechanisms.

Peripheral blood mononuclear cells (PBMCs) are a convenient human sample that can be used to screen and study the effects of different small molecules in the context of cancer.

Cytotoxicity of Drugs

Chemotherapeutics are well known yet notorious for their toxic activity on cancer cells and other naturally renewing human cells, respectively. PBMCs can be used to investigate these drugs that target rapidly dividing cells in cancer [2] and in infectious diseases (e.g. parasites) to help understand the expected clinical results later on.

Nanoparticles

In addition to the cytotoxicity of drugs, PBMCs are also a convenient source of cells to study nanoparticles! [3] Like chemotherapeutic small molecules, some of these nanoparticles may have intriguing immunologic or antitumor activity. By comparing the activity of these drugs or nanoparticles in healthy PBMCs and disease state cells, groups like Premanathan, et al. can identify selective therapy options that will be most beneficial for the patient, limiting the unnecessary off-target effects and toxicities.

Gene Expression

Are you more interested in studying cancer drug effects on the genetic or DNA level? PBMCs are great for that, too! Researchers are already using them to investigate how inhibitors influence gene expression [4] and to detect DNA damage, like dangerous double stranded breaks (DSB) that can lead to cell death or tumor formation [5]. One way DSBs are identified is through recognition of phosphorylated histone protein H2AX (γH2AX) foci, a biomarker for cancer and aging.

Aging

Brace yourself for another staggering statistic: we are all getting older, every hour of every day. The good news is that there are many groups studying how we age by looking at everything from DNA strand break repair [6] to telomere length and telomerase activity [7] or even age-related alterations in immune response [8] within PBMCs. So there may be hope for finding ways to beat cancer and slow down the inevitable aging process!  When looking for a supplier of PBMCs - think HemaCare!  We've been providing high quality blood products to researchers for over 35 years.

Don’t miss Part IV of this series, covering an exciting new approach that increases the efficiency and further improves the advantages of drug development with PBMCs on a systems level.

 

References:

[1] SEER Stat Fact Sheets: All Cancer Sites.  http://seer.cancer.gov/statfacts/html/all.html

[2] Correale, P. et al.  Journal of Clinical Oncology 23, no. 35 (2005): 8950-8958.

[3] Premanathan, M. et al.   Nanomedicine: Nanotechnology, Biology and Medicine 7, no. 2 (2011): 184-192.

[4] Yilmaz, S et al. Genomics 96, no. 1 (2010): 57-65.

[5] Willitzki, A. et al.  Cytometry Part A 83, no. 11 (2013): 1017-1026.

[6] Garm, C. et al.  Aging Cell 12, no. 1 (2013): 58-66.

[7] Invernizzi, P. et al. Digestive and Liver Disease (2013).

[8] Longo, D. et al.  The Journal of Immunology 188, no. 4 (2012): 1717-1725.

Topics: Cancer, Drug Discovery, PBMCs, Basic Research

Maria

Written by Maria

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