Targeted Vs Chemo - and targeted wins!

['lizbeth]

Well . . . I had typed up a long response and the system logged me out - as usual.

I don't quite agree with this:

Targeted therapies are typically not very effective when used singularly or even in combination with conventional chemotherapies. The targets of many of these drugs are so narrow that cancer cells are likely to eventually find ways to bypass them.

Physicians may have to combine several targeted treatments to try an achieve cures or durable responses for more complicated tumors like those that occur in the breast, colon and lung.

These targeted therapies produce limited results because they can help a relatively small subgroup of cancer patients. But when they work, they produce very good responses. With targeted therapy, the trick is figuring out which patients will respond. Tests to pinpoint those patients cannot be accomplished with genetic testing.

I feel comparatively to the success of chemotherapy, targeted treatments have significantly changed the treatments, disease free progression and overall survival for many cancer patient subgroups.

I understand about single use therapies. My good friend failed miserably on a PARP inhibitor. But she had gone through numerous treatments, alternatives. In fact, she is one of the only patients I know that was tested at Rational Therapeutics.

Part of the issue that might come up from functional profiling is to have the physician and patient on board to follow the best recommendation.

When the patient has to switch medical teams frequently to try and get the needed treatments to stay ahead of cancer and they are stage IV, stressed and ill, important decision making information seems to get lost or forgotten. Not everyone has an advocate, or a medical team that is vested in them beating cancer.

[gdpawel]

From what I remember, dopamine receptor antagonists inhibit the class of receptors that binds dopamine, a hormone and neurotransmitter. Dopamine is an emetic and can induce nausea, hence blocking dopamine receptors is another treatment of controlling chemotherapy-induced nausea and vomiting. Domperidone (commercially called Motilium) and metoclopramide (Reglan) are the two main dopamine receptor antagonists used for antiemetic treatment. Here is an excellent review on the pharmacokenetics of dopamine receptor antagonists.

http://www.pharmacorama.com/en/Secti...amines_7_4.php

I know there has been some concern about the potential for significant cardiovascular effects of the newer biologic therapies like the tyrosine kinase inhibitor sunitinib (Sutent). Patients and doctors need to get more information and they need to know the potential side effects down the road (a.k.a. tighter monitoring).

In regards to tyrosine kinase, these are very specific enzymes and therefore specific enzyme inhibitors. Most proteins in the body contain tyrosine. But tyrosine is only phosphorylated by a specific tyrosine kinase. Tyrosine is a very general amino acid. It is present everywhere. There are many, many, many tyrosine kinase inhibitors. The effects of these inhibitors is very specific. Therefore, I would not expect that most of the pharmaceutical tyrosine kinase inhibitors would have any effects at all on the neurotransmitter dopamine.

[gdpawel]

In regards to diagnostics in cancer treatment, some phenotype profiling labs, in addition to testing your tumor against a number of chemotherapeutics, can also test the effectiveness of molecularly targeted agents in treating cancer.

Scientists have come to realize that cancer biology is driven by signaling pathways. Cells speak to each other and the messages they send are interpreted via intracellular pathways known as signal transduction. Picture these pathways as if they were phone lines, linking one cell to another.

Many of these pathways are activated or deactivated by chemical reactions. In some cases, programmed cell death is inhibited when these pathways are disrupted. When the cell does not die, as it should normally, cancer forms.

In recent years, research has lead to the creation of “small molecules” to regulate these chemical reactions. Hundreds of these “targeted" agents are currently in development for cancer treatment.

While some physicians are using genomic or proteomic testing to detect mutations in these pathways, phenotype analysis labs have taken a different approach. Using functional profiling, they measure the end result of pathway activation or deactivation in the individual. They can then predict whether the "individual" cancer patient will "actually" respond to a targeted agent.

To date, their results have exceeded the reported results of those who have based treatment regimens on DNA profiles (Arienti et al. Journal of Translational Medicine 2011, 9:94).