Cancer Forums and News by PhD's


News | Forums Register

Go Back   Cancer Forums and News by PhD's > Liver Cancer Forum

Reply
 
Thread Tools Display Modes
  #1  
Old 04-14-2008, 08:03 AM
admin admin is offline
Administrator
 
Join Date: Nov 2006
Posts: 68
Default Penn researchers find targeted therapy combination overcomes treatment resistance in

A new story entry has been added:

Penn researchers find targeted therapy combination overcomes treatment resistance in liver cancer

[quote]SAN DIEGO ?? Researchers at the University of Pennsylvania School of Medicine and Abramson Cancer Center reported today at the annual meeting of the American Association for Cancer Research that combining two targeted therapies overcomes treatment resistance in liver cancer cell lines. The team is currently designing a trial to test the combination in patients. Liver cancer is resistant to many chemotherapies and to cell-death inducing agents. Last year, however, the U.S. Food and Drug Administration approved sorafenib (Nexavar
Reply With Quote
  #2  
Old 04-23-2008, 07:56 PM
gdpawel gdpawel is offline
Moderator
 
Join Date: Feb 2007
Location: Pennsylvania
Posts: 4,354
Default True Synergy

True synergy is rather uncommon in most adult solid tumors. Most drug combinations in diseases such as lung cancer, breast cancer, and ovarian cancer are merely additive, where the whole equals the sum of its parts, and not synergistic.

In hematologic neoplasms (leukemia, lymphoma, multiple myeloma), true synergy is very common. In cases where drugs are only additive and not synergistic, nothing is learned by testing the drugs in combination over what is learned by testing them separately. So drugs in combination are only tested in cases where there is the realistic possiblity of seeing true synergy.

The best combinations are those in which there is true synergy and in which the toxicities of the drugs in the combination are non-overlapping, so that full doses of each drug may be given safely.

The theory behind combination chemotherapy is that you can't give full doses of all drugs when you give them together. They have overlapping toxicity, which means you need to cut the doses when you give them together, so you get down to "homeopathic" dose levels.

Pharmaceutical companies have been attracted to studies looking at the maximum tolerated dose of any treatments. Cancer sufferers have been taking doses of expensive and potentially toxic treatments that are possibly well in excess of what they need.

Many of the highly expensive targeted cancer drugs may be just as effective and produce fewer side effects if taken over shorter periods and in lower doses. The search for minimum effective doses of treatments should be one of the key goals of cancer research.

Molecular testing methods detect the presence or absence of selected gene mutations which theoretically correlate with single agent drug activity. Tests are performed using material from dead, fixed or frozen cancer cells.

Cell culture methods assess the net effect of all inter-cellular and intra-cellular processes occurring in real-time when cells are exposed to anti-cancer agents. Tests are performed using intact, living cancer cells plated in microclusters.

Cell culture methods allow for testing of different drugs within the same class and drug combinations to detect drug synergy and drug antagonism.

Last edited by gdpawel : 02-20-2011 at 02:24 PM. Reason: additional info
Reply With Quote
  #3  
Old 02-20-2011, 02:25 PM
gdpawel gdpawel is offline
Moderator
 
Join Date: Feb 2007
Location: Pennsylvania
Posts: 4,354
Default Combination Targeted Therapy

A targeted drug agent refers to an antibody (chemical structure) that is only supposed to interact with one type of molecule in the body. The idea that a targeted drug can interact with only one pathway and work only on one cellular pathway is unlikely. Molecular pathways inside cells have an incredible amount of cross-talk. So blocking one molecule precisely is like keeping one person from talking and expecting that the rumor won't spread just as fast.

Targeted therapy halts the growth of certain cancers by zeroing in on a signaling molecule critical to the survival of those cancer cells. The drugs work specifically in patients whose cancers contain mutations in a gene that encodes the epidermal growth factor receptor (EGFR), vascular endothelial growth factor VEGF, or some other pathway. Although these targeted therapies are initially effective in a subset of patients, the drugs eventually stop working, and the tumors begin to grow again.

All the VEGF/EGFR mutation or amplification studies can tell us is whether or not the cells are potentially susceptible to this mechanism of attack. They don't tell you if one targeted drug is better or worse than some other drug which may target a specific pathway. There are differences. The drug has to get inside the cells in order to target anything.

The "cell" is a system, an integrated, interacting network of genes, proteins and other cellular constituents that produce functions. You need to analyze the systems' response to drug treatments, not just one or a few pathways. The cell "function" methodology measures the net effect of all processes within the cancer, acting with and against each other in real time, and it tests living cells actually exposed to drugs and drug combinations of interest.

The ultimate driver of the functional assay is the cell, composed of hundreds of complex molecules that regulate the pathways necessary for vital cellular functions. If a targeted drug could perturb any one of these pathways, it is important to examine the effects of the drug within the context of the cell. It allows for testing of different drugs within the same class and drug combinations to detect drug synergy and drug antagonism.

VEGF/EGFR-targeted drugs are poorly-predicted by measuring the ostansible targets, but can be well-predicted by measuring the effect of the drug on the function of live cells. True synergy is rather uncommon in most adult solid tumors. Most drug combinations in diseases are merely additive, where the whole equals the sum of its parts, and not synergistic.

The best combinations are those in which there is true synergy and in which the toxicities of the drugs in the combination are non-overlapping, so that full doses of each drug may be given safely.
__________________
Gregory D. Pawelski

Last edited by gdpawel : 03-19-2011 at 03:58 AM. Reason: revise
Reply With Quote
Sponsored Links
Advertisement
Reply


Thread Tools
Display Modes

Posting Rules
You may not post new threads
You may not post replies
You may not post attachments
You may not edit your posts

vB code is On
Smilies are On
[IMG] code is On
HTML code is Off
Forum Jump


All times are GMT -5. The time now is 05:46 PM.