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gdpawel
06-24-2005, 02:07 PM
Targeted treatments like Iressa and Tarceva, take advantage of the biologic differences between cancer cells and healthy cells by "targeting" faulty genes or proteins that contribute to the growth and development of cancer. Many times these drugs are combined with chemotherapy, biologic therapy (immunotherapy), or other targeted treatments.

Clinicians have learned that the same enzymes and pathways are involved in many types of cancer. However, understanding targeted treatments begins with understanding the cancer "cell." In order for cells to grow, divide, or die, they send and receive chemical messages. These messages are transmitted along specific pathways that involve various genes and proteins in the cell.

Cancer cells often have many mutations in many different pathways, so even if one route is shut down by a targeted treatment, the cancer cell may be able to use other routes.

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.

All the gene amplification studies, via genetic testing, tell us is whether or not the cancer cells are potentially susceptible to a mechanism/pathway of attack. They don't tell you if one drug (Iressa) is better or worse than another drug (Tarceva) which may target a certain mechanism/pathway. Cell-based functional analysis can accomplish this, or the physician can "trial-and-error" what will work. That's up to the patient.

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 target or pathway, or even a few targets/pathways.

Literature Citation:

Functional profiling with cell culture-based assays for kinase and anti-angiogenic agents Eur J Clin Invest 37 (suppl. 1):60, 2007

Functional Profiling of Human Tumors in Primary Culture: A Platform for Drug Discovery and Therapy Selection (AACR: Apr 2008-AB-1546)

gdpawel
02-28-2011, 05:28 PM
Gefitinib Improves Progression-free Survival for Metastatic Lung Cancers with EGFR Mutations

Patients newly diagnosed with metastatic non-small cell lung cancer (NSCLC) who received gefitinib (Iressa) had significantly higher response rates and longer progression-free survival compared with patients who received carboplatin plus paclitaxel (73.7 percent versus 30.7 percent and 10.8 months versus 5.4 months, respectively), according to results of a phase III trial conducted in Japan. The results were published in the June 24, 2010 New England Journal of Medicine.

All patients enrolled in the study had epidermal growth factor receptor (EGFR) mutations that were sensitive to the tyrosine kinase inhibitor (TKI) gefitinib. The patients did not have the resistant EGFR mutation T790M, and they had not been previously treated with chemotherapy.

The researchers, led by Dr. Makoto Maemondo of the Miyagi Cancer Center in Miyagi, Japan, believe that this study establishes the clinical benefit of an EGFR tyrosine kinase inhibitor as first-line therapy in patients with NSCLC and sensitive EGFR mutations.“If gefitinib is administered as second-line or third-line treatment,” he and his colleagues wrote, “patients may miss the opportunity to receive treatment because of rapidly progressive disease during or after first-line treatment.”

The trial was stopped early in 2009 after a planned interim analysis of the first 200 patients revealed a 70 percent reduction in disease progression or death in patients receiving gefitinib. Ultimately, 230 patients from 43 institutions in Japan were enrolled and analyzed. At 1 year, 42.1 percent of patients receiving gefitinib had not progressed, compared with 3.2 percent of those receiving chemotherapy; after 2 years, all chemotherapy patients had progressed, while 8.4 percent of those receiving gefitinib still had not. Women had significantly longer progression-free survival than men.

Patients who completed their first-line therapy or whose disease progressed while receiving chemotherapy were allowed to cross over and receive gefitinib, and 106 out of 112 did so. Fifty-nine percent of these patients responded to second-line therapy with gefitinib. This crossover, the researchers wrote, may have affected the overall survival difference between the two study arms, which was not statistically significant.

Gefitinib fell out of favor in the United States after a 2005 clinical trial indicated the drug had little benefit in unselected patients, and the drug currently has a very restricted label in this country, where erlotinib (Tarceva) is the approved second-line EGFR TKI of choice. Both gefitinib and erlotinib work in a similar way, and patients with sensitive EGFR mutations are also very responsive to erlotinib treatment.

http://www.cancer.gov/clinicaltrials/results/gefitinib-NSCLC0810

gdpawel
02-28-2011, 05:30 PM
New data presented at ASCO 2008 from TRUST1, the largest non-small cell lung cancer (NSCLC) Phase IV trial ever conducted, show that a broad range of NSCLC patients treated with Tarceva (erlotinib) experience clinical benefits including longer survival, better quality of life, control of disease symptoms and control of cancer progression. NSCLC is the most common and deadly form of lung cancer suffered by over one million people worldwide.

http://www.medicalnewstoday.com/articles/109387.php

Realizing Tarceva's Potential

Targeted treatments like Tarceva, take advantage of the biologic differences between cancer cells and healthy cells by "targeting" faulty genes or proteins that contribute to the growth and development of cancer. Many times these drugs are combined with chemotherapy, biologic therapy (immunotherapy), or other targeted treatments.

Clinicians consider the biology of the tumor cell along with the site of the tumor when determining treatment. They are learning that the same enzymes and pathways are involved in many types of cancer. However, understanding targeted treatments begins with understanding the cancer cell. In order for cells to grow, divide, or die, they send and receive chemical messages. These messages are transmitted along specific pathways that involve various genes and proteins in a cell.

Targeted treatments fight cancer by correcting or modifying defective pathways in a cancer cell. In healthy cells, each pathway is tightly controlled. In cancerous cells, certain points in the pathway become disrupted, usually through a genetic mutation (change in form).

Serious consequences to the cell may result from these mutations, depending on which pathway is affected. For example, suppose a cell develops a mutation that causes it to continue dividing into new cells? In other words, the signal is always on. If the signal never turns off, the cells that keep growing may eventually form a tumor.

Because many cancer cells use similar pathways, the same drug could be used to treat one person's breast cancer and another person's lung cancer, as long as each tumor contained similar targets. This is why many of these treatments are being used in a variety of cancer types.

There is a challenge though, to identify which patients the targeted treatment will be effective. Initially, when Iressa or Tarceva was used in patients with lung cancer, researchers discovered that only patients whose tumors contained specific mutations responded to the drug. This new research data may confirm that this is not necessarily true. Patients across a broad range of clinical characteristics could benefit.

The introduction of targeted drugs has not been accompanied by specific predictive tests allowing for a rational and economical use of these drugs. However, given the technical and conceptual advantages of cell-based functional analysis, together with its performance and the modest efficacy of therapy prediction on analysis of genome expression, there is reason for a renewal in the interest of Oncologic In Vitro Chemoresponse Assays for optimized use of medical treatment of malignant disease.

gdpawel
02-28-2011, 05:33 PM
The cancer drug Iressa actually does work miracles, in some patients. Cell culture analysis has been able to find the cellular signal for response to the drug and can identify clinical responders - prospectively.

The Iressa situation is a great argument for pre-screening an individual's tumor. Iressa has been shown to benefit those that are benefitting from it. If the drug is working for some people, then obviously there are others out there who would also benefit. Who are those that benefit from its use? All the more reason to test the tumor first.

Assay-directed therapy is an individualized approach to killing cancer. The bio-marker method is used to determine what precise medications would kill the particular cancer. Doctors have assumed that stopping cell division would stop cancer, because most cancer cells divide and grow rapidly. But the approach didn't always kill the malignant cells. Cancer isn't a case of cells growing out of control, but of cells refusing to die on schedule.

By inhibiting anti-apoptosis with Iressa (small molecule inhibitor of tyrosine kinase, a key intermediary in the EGF cascade pathway), the cells undergo apoptosis and die. This can be detected at the whole cell level and reported out prospectively. It is a unique tool for identifying newer, better drugs, testing drug combinations, and serving as a "gold standard" to develop new DNA, RNA, and protein-based tests of drug activity.

The EGF system is a target for a number of newer anti-cancer drugs. However, EGF-targeted drugs like Iressa are poorly-predicted by measuring the ostensible target (EGFR), but can be well-predicted by measuring the effect of the drugs on the "function" of live cells. It is an area of cancer research which has been abandoned by the entire cancer research establishment. A bioengineering problem overcomed by a band of private-lab cell biologists.

More and more physicians and patients are turning to individualized therapies to treat cancers. Under this approach, scientists study how an individual's cancerous cells respond to several drugs. Doctors have learned that even when the disease is the same type, different patients' tumors respond differently to chemotherapeutic drugs. Without individualized testing, it's difficult to determine which drugs are best for patients who don't respond to standard therapies.

There are over numerous different therapeutic drug regimens out there. Any one or combination of them can help cancer patients. The system is overloaded with drugs and under loaded with wisdom and expertise for using them. What's needed is to make extensive use of bio-marker tests in treatment decisions.

Literature Citation: Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 17117

gdpawel
02-28-2011, 05:35 PM
The introduction of targeted therapies now provides select patients the opportunity to receive first-line therapies with these new classes of drugs. The recognition that epidermal growth factor tyrosine kinase inhibitors are most effective in patients with EGFR mutations (codons 19-21) has enabled us to apply the EGFR mutation analysis as a biomarker for response.

Despite the high response rates (up to 70% in mutation positive patients), approximately 30% of patients with the appropriate biomarker do not respond. In addition, patients who do not carry EGFR mutations can nonetheless respond to these classes of drugs. This reflects the complexity, redundancy and promiscuity of signal pathways, such that, pathway cross talk has the capacity to salvage cancer cells from the lethal effects of these inhibitors.

The functional profiling platform has the unique capacity to identify all of the operative mechanisms of response and resistance by gauging the result of drug exposure at its most important level: cell death. The earliest work of Dr. Robert Nagourney, Iressa (gefitinib) conducted in 2001, identified non-small lung cancer as an important target disease.

As he continued his work with Iressa (gefitinib) and Tarceva (erlotinib), he had the opportunity (under IRB-approved protocol) to treat patients with first line Tarceva. To date, he is tracking a 100% response rate to Tarceva in the select populations; even patients who have not been found to carry recognized mutations.

More interesting, patients not expected to respond, such as one multiply recurrent male smoker has remained in a 4 year remission on Tarceva as a third line therapy. As predicted by functional profiling analysis, the emerging study of combined signal inhibitors provides the opportunity to examine favorable combinations for effect and synergy.

The rational combination of signal inhibitors is a highly productive avenue of research under investigations in many centers, including at the Rational Therapeutics laboratory. Consistent with their presentation at a meeting of the American Association for Cancer Research, the dual inhibition of the P13k and EGFR pathways may prove highly productive. This work is ongoing at Rational Therapeutics.

Source: Nagourney, R. et. al, Horizontal and vertical signal pathway inhibition in human tumor primary culture micro-spheroids. Abstract 1764, proceedings AACR 2010.

pbj11
03-01-2011, 12:32 AM
I knew that Tarceva often had some effectiveness for patients without the EGFR mutation, but guess I didn't realize that such a high percentage with the mutation have no benefit. Interesting.

Bottom line is, even without the mutation, Tarceva still should be considered as a viable part of the arsenal against NSCLC. I'm glad our oncologist was willing to give it a try, even though there was no response. I hope that future health care plans won't require the EGFR mutation be present in order for a patient to try Tarceva, when it clearly shows a significant enough benefit.

gdpawel
03-01-2011, 01:13 AM
Unfortunately, I've been reading posts across the cancer boards of patients finding out that by just having the EGFR mutation, it doesn't mean that Tarceva "will" work. Even with the exon 19 or 21 which is supposed to respond well to Tarceva. Genetic testing cannot do this for the individual. All an EGFR mutation study can tell you is whether or not the cancer cells are "potentially" susceptible to this mechanism of attack. It cannot tell you if Tarceva will actually work for your cancer cells, or not, or if some other EGFR-inbititing drug will. Tumor cells have such an uniqueness that not much is known of their respective reaction to targeted therapies.

Greg

pbj11
03-01-2011, 01:33 AM
What's more striking to me is how some without the mutation actually respond, usually in terms of stable disease.

I'm far more simplistic about cancer. There's only one rule -- there are no rules.

Often went through bumps with my husband and have seen others that fall into the 'no rhyme or reason' category for why peculiar things happen during a course of treatment.

Tarceva and the uniqueness of each person's cancer is evident in how long some people who do respond, benefit from it vs. others who show response and then suddenly stop. The variables just go on and on. The more I read and learn, the farther away a real resolve to this beast seems to me sometimes. I know they are getting deeper into things, but the complexities are mind blowing.

gdpawel
03-01-2011, 01:51 AM
And don't forget, Avastin for radiation-induced necrosis (go figure). Read about it in the Brain Cancer boards under New Perspectives for Brain Metastasis.

maryaz
03-01-2011, 03:37 AM
I just made a bunch of posts and this slipped down the list. I wanted to bump it back up for others to read. I, personally, feel this is an important topic. I read some and will finish later. When I first came back to this forum this year, I searched Tarceva and this is the thread I found, lacking today's posts, of course. (grin)

Pbj, I am glad you said all that you did about the confusion with this disease. That will save me time trying to figure out if it was just me and a slow thinking mind. It really is no rules. If I am right, Joe will have a few choices to try from if the current chemo quits working.

Thanks to all of you that do so much for all of us still fighting.

CancerStinks
04-05-2011, 10:04 PM
Hello,

My brother (age 51) was recently diagnosed with Stage IV non-small cell lung cancer (adenocarcinoma). Oncologist believes it has spread to lymph nodes outside his lung and also his hip bone.

We were not given many options by the local oncologist (basically have some chemo to slow things down, go home and die).

We are now being treated at the Mayo Clinic and have more hope. The first thing the oncologist at Mayo wanted to do is some genetic testing to see if my brother's cancer has a gene mutation. He explained that there are multiple targeted therapy drugs to attack these cancers. (The local oncologist NEVER mentioned this possibility).

They are testing for: ALK, EGFR, and K-RAS. Are these the only 3 that should be tested for? It sounds like there are amazing results for some patients when you match a targeted therapy drug to your specific gene mutation cancer. Amazing detective work.

Anyone else been through this and has some advice? He's had one chemo infusion (carboplatin, Avastin, Alimta) so far while we wait for the test results.

Thank you!

pbj11
04-05-2011, 10:10 PM
Hi,

GD Pawel posts the most up to date information on what is happening, so I'd think this is the whole ball of wax for the moment.

They were not doing these tests routinely when my husband was diagnosed. I have seen other posters talk about these mutation tests being run on their loved ones.

Make sure you read the caveats about response with and without mutations. Remember the one rule about lung cancer -- there are no rules.

Keep us posted as to his results.

God bless,
PBJ

gdpawel
04-05-2011, 10:59 PM
There truly are amazing results for some "subsets" of cancer patients when you match a targeted therapy drug to your specific gene mutation.

Genetic testing attempts to figure out the "recipe" for your cancer. If it turns out that you have a certain mutation, statistically you may be more likely to respond to a particular treatment. But that is only based on statistics - what worked for other people with a similar cancer recipe.

It only gives you some idea of what clinical trials might be effective on your particular tumor. All DNA or RNA-type tests are based on "population" research (not individuals). They base their predictions on the fact that a higher percentage of people with similar genetic profiles or specific mutations may tend to respond better to certain drugs. This is not really "personalized" medicine, but a refinement of statistical data (still "trial-and-error therapy).

Cancer is more complex than its gene signature. Contained within the genes of each human is the information to create every protein, every enzyme, every lipid, every carbohydrate and all the organs and systems dependent upon their function.

What is not known is how all of those 25,000+ genes are regulated to produce the unique features that constitute us as human entities. Human beings are demonstrably more than the sum of their genes. Cancer biology and the study of cancer therapy are many things, but simple is not one of them.

One of the hallmarks of cancer is the complex interaction of genes, networks, and cells in order to initiate and maintain a cancerous state. This inherent complexity constantly challenges our ability to develop effective and specific treatments. A systems biology approach towards the understanding and treatment of cancer examines the many components of the disease simultaneously.

Are ALK, EGFR and KRAS enough? No. You might need to test for the 15 or 20 gene mutations that may be involved in determing sensitivity/resistance to a given drug (that's 15 to 20 tests). Because if you miss just one, that might be the one which continues cancer growth. There are two main technologies involved for sensitivity and reproducibility: real-time polymerase chain reaction, or RT-PCR and DNA microarray.

Testing for pathways (molecular profiling), those which identify DNA, or RNA sequences or expression of individual genes or proteins often examine only one component of a much larger, interactive process. It doesn't matter if there is a target molecule in the cell that the targeted drug is going after. If the drug either won't "get in" in the first place or if it gets pumped out/extruded or if it gets immediately metabolized inside the cell, drug resistance is multifactorial.

You can though take the advantage of profiling the entire cell to measure the interaction of the entire genome (not just one pathway or a couple of pathways). There are many pathways to altered cellular (forest) function (hence all the different "trees" which correlate in different situations). Functional profiling the whole cell measures what happens at the end (the effects on the forest), rather than the status of the individual trees.

Cancer is a complex disease and needs to be attacked on many fronts. Improving cancer patient treatment through proper drug selection will enable oncologists to prescribe treatment more in keeping with the heterogeneity of the disease. The biologies are very different from patient to patient and the response to given drugs is very different.

The "choice" is yours.

Greg

pbj11
04-06-2011, 12:10 AM
Greg,

Thanks! I'm sure glad you stay on top of this information, because it makes my head spin. Although the three mutations are not enough, are they all that are currently identified and tested?

PBJ

gdpawel
04-06-2011, 01:27 AM
PBJ

Unfortunately, as I stated above, just having (for instance) the EGFR mutation doesn't mean that Tarceva "will" work. Genetic testing cannot do this for the individual. All a mutation study can tell you is whether or not the cancer cells are "potentially" susceptible to this mechanism of attack. It cannot tell you if Tarceva will actually work against your cancer cells, or not, or if Iressa will. Tumor cells have such an uniqueness that not much is known of their respective reaction to targeted therapies.

This is because of the complexity, redundancy and promiscuity of signal pathways, in that pathway cross-talk has the capacity to salvage cancer cells from the lethal effects of these protein inhibitors. Functional profiling can identify all of the operative mechanisms of response and resistance by gauging the result of drug exposure at the endpoint: cell-death. The core of functional profiling 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 would be important to examine the effects of a targeted drug within the context of the cell. Both genomic and proteomics can identify potential new therapeutic targetes, but these targets require the determination of cellular endpoints. One of the hallmarks of cancer is the complex interaction of genes, networks, and cells in order to initiate and maintain a cancerous state. This inherent complexity constantly challenges our ability to develop effective and specific treatments. A systems biology approach towards the understanding and treatment of cancer examines the many components of the disease simultaneously.

There is really no right mutation or wrong mutation. There are the right drugs and the wrong drugs. There are "sensitive" drugs and there are "resistant" drugs. Patients would certainly have a better chance of success had their cancer been "chemo-sensitive" rather than "chemo-resistant" where it is more apparent that chemotherapy improves the survival of patients, and where identifying the most effective chemotherapy would be more likely to improve survival.

Yes! It does make one's head spin. No. They have currently identified, and are continuously identifying numerous mutations with names that will really make the head spin. Look at some for breast and ovarian cancers (mTOR/P13K and MEK/ERK inhibitors). I can't keep track!

Greg

pbj11
04-06-2011, 03:05 AM
Thanks Greg. I often have to read your posts multiple times to get a sense of what you are saying, as these areas are above my pay grade. (I've become a dinosaur in the span of 5+ years, which actually is a good thing for the field of cancer research.) I do try to impress upon the folks here what you have outlined in your first paragraph. That is of paramount importance for people to understand.

While targeted therapy is certainly a quantum advancement, we can't dismiss the results that are obtained with traditional agents either. My fear is that people are leapfrogging over traditional therapies in hope of the significant gain with the targeted therapies. As you've noted, they are promising, can work absolute wonders for some, but aren't the be all and end all due to the variables of each person's physiology. The bigger point here is, through tissue testing, people are no longer flying in the dark regarding expectations for treatment to work.....or are they? Therein lies the rub.

I'm so thankful that it's you and not me tracking all of these new twists in research! As usual, your contributions are invaluable here.

Best regards,
PBJ

maryaz
04-10-2011, 02:54 AM
I would like to be able to say that I was reading it also but I cannot. It looks like really good info. If I need it I will come back but it is so over my head. I would have to dissect it. I scan over it.

CancerStinks
04-20-2011, 12:47 PM
Greg,

Thank you so much for all that information! I'm going to re-read it a few times to make sure I understand it.

My brother's EGFR, KRAS, and ALK tests all came back negative. He is half way through the 4-chemo infusion treatment plan and will have a CT scan next week to compare to the baseline (before chemo) CT scan.

Any new drugs for lung cancer in the clinical trial pipelines that I should read up on?

Thanks!

-Cathy

gdpawel
04-20-2011, 03:56 PM
Cathy

Testing for EGFR, KRAS and ALK pathways and coming up negative is no reason not to be given these drugs. For example, the FDA approved indication for the EGFR inhibitor Tarceva does not limit prescribing specifically to EGFR positive patients. In the registration trial, only one third of the patients were tested for EGFR and determining response based on EGFR was not a major endpoint of the study.

Testing for the EGFR mutation may be able to tell you whether or not your cells are "potentially" susceptible to this mechanism of attack. It cannot tell you if Tarceva will work for "your" individual cancer cells. It is still a "trial-and-error" approach to therapy. Personally, I would not want to be denied treatment with any targeted therapy because of a gene mutation or amplification study. It is not a clear predictor of benefit or a lack of benefit.

Rather than only give Tarceva to all patients with EGFR positive NSCLC, it could be given selectively to patients with EGFR negative NSCLC or to patients with all types of cancer, if it otherwise indicated and if a functional assay is positive for it. It could be vastly more beneficial to measure the net effect of all processes instead of just individual molecular targets. It looks at the entire cell to measure the interaction of the entire genome, not just one pathway or a couple of pathways.

The cell is a system, an integrated, interacting network of genes, proteins, and other cellular constituents that produce functions. One needs to analyze the systems' response to drug treatments, not just one or a few targets (pathways/mechanisms).

There are many pathways/mechanisms to the altered cellular (forest) function, hence all the different "trees" which correlate in different situations. Improvement can be made by measuring what happens at the end (the effects on the forest), rather than the status of the indivudal trees.

I don't know what four-drug combination your mother is receiving, but if she was not given any EGFR, KRAS or ALK inhibitior drugs, she could have missed out on some very beneficial (active) drugs. I'm not saying they would have been beneficial, without a functional assay, but they could have. Let's hope her CT scan will show what she was given was sensitive to her individual cancer cells.

In regards to new drugs for lung cancer, there is really no right mutation (positive) or wrong mutation (negative), there are the right drugs and the wrong drugs. There are "sensitive" drugs and there are "resistant" drugs. There is no lung cancer chemo, or breast cancer chemo, or ovarian cancer chemo. There is chemo that is sensitive (effective) or resistant (ineffective) to each and every "individual" cancer patient, not populations. There are chemos that share across tumor types.

Greg

Spouse
02-07-2013, 10:27 AM
I hope that future health care plans won't require the EGFR mutation be present in order for a patient to try Tarceva, when it clearly shows a significant enough benefit. My husband is EGFR negative (that is, "wild", if I have the terms figured out correctly), and his drug insurance approved Tarceva for 3rd line therapy. We'll see how it works for him when he has a CT in about a month.

gdpawel
02-07-2013, 05:03 PM
Spouse

In regards to "wild-type," cancer cells have membrane receptors that specialize in membrane proteins that take part in communication between the cell and the outside world. Extracellular signaling molecules attach to the receptor, triggering changes in the function of the cell.

This process is called signal transduction. The binding initiates a chemical change on the intracellular side of the membrane. In this way the receptors play a unique and important role in cellular communications and signal trasduction.

The "wild-type" EGFR receptor typically sends a downstream signal that ultimately stimulates the growth of the NSCLC cells that are dependent on the receptor, and Iressa or Tarceva can modestly inhibit this relatively weak signal.

The "mutated" EGFR receptor is constitutively activated with a prominent downstream signal that can be dramatically inhibited by Iressa or Tarceva.

Researchers suspect that the "wild-type" receptor causes the diarrhea and skin side effects from using drugs like Iressa and Tarceva.

Pharmacogenomics is a field that studies how a person's genetic makeup determines response to a drug. This area was ripe for proprietary tests, invented alongside a drug and owned by the drug developer and/or a partner in the diagnostics field.

This "business opportunity" evolved as more drugs were approved with what are called "companion diagnostics." Unfortunately, the introduction of these new drugs has not been accompanied by good, specific predictive tests allowing for a rational and economical use of these targeted drugs.

"Companion diagnostics" are tests linked to a therapeutic drug that stratify populations into responders and non-responders.

However, "companion diagnostics" tend to only answer a targeted drug-specific question and may not address other important clinical decision needs. They are being used to predict responsiveness and determine candidacy for a particular therapy often included in drug labels as either required or recommended testing prior to therapy initiation.

Surveys done by the Tufts Center for the Study of Drug Development showed lack of evidence concerning the clinical usefulness of many current companion diagnositcs and a major factor limiting the potential of personalized medicine.

And reimbursement issues have limited uptake in clinical practice with respect to these companion diagnostics. Companion diagnostics and their companion therapies are what's being pushed as "personalized medicine."

The idea of simply finding a mutation and then pick an appropriately targeted drug seems like a nice idea, but not every key that looks like it will fit will actually turn it. However, if Tarceva is "sensitive" (effective) against your husband's individual cancer cells, it should work pretty well.

Greg

Spouse
02-07-2013, 11:46 PM
Thanks Greg. He's giving it a try, he'll do a follow up CT in a month or so. Whew, each chapter of this disease, with differing chemo and therapies, bring more to learn.