Featured Research

from universities, journals, and other organizations

Epigenetic Drugs: Promising For Breast Cancer Treatment

Date:
December 26, 2006
Source:
Public Library of Science
Summary:
Worldwide, cancer persists as one of the most important diseases that affect the human being. The knowledge on the molecular bases of cancer generated during the last decades has been successfully translated into small but significant gains in overall cancer survival rates due to better primary prevention measures, improved diagnostic methods and the development of more effective and specific therapies, collectively termed "molecular targeted therapies." In the context of these new forms of treatment, epigenetic or transcriptional cancer therapy is clearly promising.

Worldwide, cancer persists as one of the most important diseases that affect the human being. The knowledge on the molecular bases of cancer generated during the last decades has been successfully translated into small but significant gains in overall cancer survival rates due to better primary prevention measures, improved diagnostic methods and the development of more effective and specific therapies, collectively termed "molecular targeted therapies". In the context of these new forms of treatment, epigenetic or transcriptional cancer therapy is clearly promising.

Epigenetics refers to the function of DNA that does not depend on the coding DNA sequence itself but on the accessory molecules and mechanisms affected by DNA. It is known that epigenetic alterations are equally if not more important than classical genetic alterations to disrupt the function of tumour suppressor genes.The two most studied epigenetic aberrations common to all types of cancer are DNA hypermethylation and histone deacetylation, which cooperate to silence the expression of tumour suppressor genes, just as gene mutations and gene deletions do. The big difference between these two alternative ways that tumour cells use to inactivate tumour suppressor genes is that, while the reversal of genetic alterations is technically almost unfeasible in clinical scenarios, the function of these epigenetically inactivated suppressor genes is easily reactivated by pharmacological means.In this inaugural issue of PLoS ONE, Dr. Dueñas-Gonzalez's group from the Instituto de Investi gaciones Biomédicas of the Universidad Nacional Autónoma de México and the Instituto Nacional de Cancerología, Mexico, demonstrate, for the first time, that a combination of a DNA methylation and a histone deacetylase inhibitor, can reactivate the expression of more than a thousand genes in primary tumours of breast cancer patients.

Among these reactivated genes are those implicated in the regulation of cell proliferation, cell differentiation, programmed cell death, invasion, metastasis and immune recognition of tumour cells, such as p53, p21, eighteen members of the oxidative phosphorylation pathway, interferon-regulatory factors, NM23, negative regulators of Wnt signalling and Major Histocompatibility Complex Class-I and --II genes.In addition, these drugs down-regulate genes such as ABCB5, a recently identified member of the ABC transporter family implicated in multidrug resistance, which is predominantly expressed by tumour "stem" cells. Moreover, in this proof-of-principle study, the Mexican researchers demonstrate that this combination of epigenetic drugs can be safely administered concurrently with classical cytotoxic agents such as doxorubicin and cyclophosphamide, a common drug combination employed in the primary treatment of breast cancer.

Although this study is suggestive of increased anti-tumour effects no definitive conclusions can be drawn from it regarding the clinical efficacy of this therapy, because the study is single arm and the number of patients small; however, it is clearly suggestive that the epigenetic "principle" works and calls for increased preclinical and clinical efforts toward epigenetic cancer therapy.

Researchers used "epigenetic" drugs routinely employed for non-malignant conditions

One important aspect of this study, considers Dr Dueñas-Gonzalez, is that the "epigenetic" drugs used, are "very-well known" and have been routinely employed for almost 30 years to treat non-malignant conditions: the antihypertensive hydralazine and the antiepileptic valproic acid. Advocacy groups are claiming that "big pharma" companies are not interested in pursuing the preclinical and clinical development of this type of drugs --regardless of their potential antitumour efficacy-- simply because they cannot be protected by patents and in consequence huge revenues cannot be expected. If the antitumour efficacy of these epigenetic drugs is eventually demonstrated, they would not only be added to the current anticancer armamentarium, but they will surely be affordable to the vast majority of cancer patients living in low and middle income countries, who find the newer anticancer agents prohibitively expensive. Dr Dueñas-Gonzalez's group has recently completed a couple of single arm studies of this therapy with similar results and launched three placebo-controlled randomised trials in breast, ovarian and cervical cancer patients.

Citation: Arce C, Pérez-Plasencia C, González-Fierro A, de la Cruz-Hernández E, Revilla-Vázquez A, et al (2006) A Proof-Of-Principle Study of Epigenetic Therapy Added to Neoadjuvant Doxorubicin Cyclophosphamide for Locally Advanced Breast Cancer. PLoS ONE 1(1): e98. doi:10.1371/journal.pone.0000098 (http://dx.doi.org/10.1371/journal.pone.0000098)


Story Source:

The above story is based on materials provided by Public Library of Science. Note: Materials may be edited for content and length.


Cite This Page:

Public Library of Science. "Epigenetic Drugs: Promising For Breast Cancer Treatment." ScienceDaily. ScienceDaily, 26 December 2006. <www.sciencedaily.com/releases/2006/12/061221074633.htm>.
Public Library of Science. (2006, December 26). Epigenetic Drugs: Promising For Breast Cancer Treatment. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2006/12/061221074633.htm
Public Library of Science. "Epigenetic Drugs: Promising For Breast Cancer Treatment." ScienceDaily. www.sciencedaily.com/releases/2006/12/061221074633.htm (accessed July 25, 2014).

Share This




More Health & Medicine News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) — The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) — Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com
Condemned Man's US Execution Takes Nearly Two Hours

Condemned Man's US Execution Takes Nearly Two Hours

AFP (July 24, 2014) — America's death penalty debate raged Thursday after it took nearly two hours for Arizona to execute a prisoner who lost a Supreme Court battle challenging the experimental lethal drug cocktail. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
Can Watching TV Make You Feel Like A Failure?

Can Watching TV Make You Feel Like A Failure?

Newsy (July 24, 2014) — A study by German researchers claims watching TV while you're stressed out can make you feel guilty and like a failure. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

    Health News

      Environment News

        Technology News



          Save/Print:
          Share:  

          Free Subscriptions


          Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

          Get Social & Mobile


          Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

          Have Feedback?


          Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
          Mobile iPhone Android Web
          Follow Facebook Twitter Google+
          Subscribe RSS Feeds Email Newsletters
          Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins