National Heritage Insurance Company (NHIC), the contractor that administers Medicare programs in California, has established a positive coverage policy for Cell Culture Assay Tests known as Chemosensitivity (Resistance) Testing or Oncologic In Vitro Chemoresponse Assays for a tumor specimen from a Medicare patient obtained anywhere within the United States, but submitted for testing by one of the approved laboratories located within Southern California. Medicare bills for this testing are billed through NHIC because the test is conducted by the approved laboratories in California.
This pre-test can help see what treatments have the best opportunity of being successful for "high" risk cancer patients. The test measures the response of "live" tumor cells to drug exposure. Following this exposure, the assays measure both cell metabolism and cell morphology (Functional Profiling). The integrated effect of the drugs on the whole cell, resulting in a cellular response to the drug, measuring the interaction of the entire genome. Assays based on "cell-death" occur in the entire population of tumor cells.
This cell culture assay technology has been clinically validated for the selection of optimal chemotherapy regimens for individual patients. It is a laboratory analysis based on tumor tissue profiling that uses "fresh" human tumor biopsy or surgical specimen to determine which drugs or combinations of chemotherapeutic agents have the highest likelihood of response for individual cancer patients.
Following the collection of "fresh" tumor cells obtained from surgery or tru-cut needle biopsies, a cell culture assay is performed on the tumor sample to measure drug activity (sensitivity and resistance). This will pinpoint which drug(s) are most effective. Tissue, blood, bone marrow, and ascites and pleural effusions are possibilities, providing tumor cells are present. At least one gram of fresh tissue is needed to perform the tests, and a special kit is obtained in advance from the lab. The treatment program developed through this approach is known as assay-directed therapy.
Individualized assay-directed therapy is based on the premise that each patient's cancer cells are unique and therefore will respond differently to a given treatment. This is in stark contrast to standard or empiric therapy, which chemotherapy for a specific patient is based on average population studies from prior clinical trials.
The decision had been made that the assay is a perfectly appropriate medical service, worthy of coverage on a non-investigational basis. What is of particular significance is that they abandoned the artificial distinction between "resistance" testing and "sensitivity" testing and are providing coverage for the whole FDA-approved kit. Drug "sensitivity" testing is merely a point a little farther along on the very same continuum which "resistance" testing resides.
Cell cuture assay tests based on "cell-death" have proven very effective in identifying novel treatment combinations for a variety of cancers. The value of cell-death assays is that they can and do accurately predict clinical outcomes and define novel chemotherapeutic synergies. It can help see what treatments will not have the best opportunity of being successful (resistant) and identify drugs that have the best opportunity of being successful (sensitive).
The current clinical applications of in vitro chemosensitivity testing is ever more important with the influx of new "targeted" therapies. Given the technical and conceptual advantages of "functional profiling" of cell culture assays together with their performance and the modest efficacy for therapy prediction on analysis of genome expression, there is reason for renewed interest in these assays for optimized use of medical treatment of malignant disease.
The payment provided will be sufficiently realistic that all Medicare patients for whom this testing is indicated will be able to get it with only the routine 20% co-payment, as Medi-gap insurance secondaries are mandated to provide payment for co-pays for Medicare-approved services.
The coverage became effective for claims for services performed on or after February 19, 2007. The decision is posted at:
NHIC Medicare Services reimburses qualified laboratories in Southern California for cell culture assay tests on a Medicare patient anywhere in the United States.
Likewise, Highmark Medicare Services reimburses a qualified laboratory in Pennsylvania for cell culture assay tests on a Medicare patient anywhere in the United States.
NHIC has jurisdiction over Southern California, so that is who gets billed when the laboratory is located in California.
Highmark has jurisdiction over laboratories in Pennsylvania, so that is who gets billed when the laboratory is located in Pennsylvania.
The coverage decision is posted at:
Mesothelioma may be a relatively rare disease but for those effected, it can alter your lives and the lives of your loved ones, drastically and irrevocably. This article gives the true picture about the alarming rate at which mesothelioma is increasing in the US and around the world.
Outline of Topic
BENEFIT OF SALVAGE THERAPY
The blood brain barrier
Clinical trial design
Defining treatment activity in phase II trials
Phase III testing
Evaluation of QOL during treatment
Analysis of phase III trial outcomes
Single agent chemotherapy
SUMMARY AND RECOMMENDATIONS
by Joyce Meyer
There is no fear, in love [dread does not exist], but full-grown (complete, Perfect) love turns fear out of doors and expels every trace of terror! For fear brings with it the thought of punishment, and [so] he who is afraid has not reached the full maturity of love [is not yet grown into Love's complete perfection]. 1 John 4:18
In years past, when I read this scripture, I misunderstood its meaning. I thought it was saying that if I could reach the place where I walked in perfect love towards other people, I would no longer experience fear in my own life. I diligently tried to love others, but it seemed like I always fail. I could not even love them imperfectly, let alone perfectly!
I had a lot of fear in my life fear that manifested in insecurity and mental torment of every kind. A person, who is fearful, worries. He is anxious about many things. The past, the future, finances, what people think, etc., these are his constant companions, which literally bring torment. The King James version of I John 4:18 certainly describes fear accurately when it says that, "fear hath torment."
There are many evil spirits that Satan uses to make people miserable, but I personally believe that fear is the master spirit. Fear seems to be the root of most of the problems that steal our peace. For example, if we find ourselves uncomfortable in a group of people, it is usually because we fear what they think of us. If we are trying to control a situation and it is causing us to get into strife, it is often because we are afraid that we will be taken advantage of, if we don't control everything.
THE CONTROL ISSUE
Trying to control people, circumstances, and even God is a hard task. As a matter of fact, it is impossible. Out of fear, I spent many years trying to control everything and everyone. I was fearful of being hurt or taken advantage of, as I had been in the past. I had not yet learned about "perfect love that casts out fear." I was busy being in charge of everything being the great choir director of my life. The Holy Spirit wants to guide, direct, and control us. If we allow Him, He will direct us into great blessings for our lives. We are to operate in self-control and give the Holy Spirit control of our lives, but we should never try to control other people. Satan uses manipulation and control to get his way, but these are not the methods that God's children should use to get what they desire.
We are to trust God, pray about what we want, and believe that He will do the best for us at the right time. This is difficult to learn because all too often our experience with people teaches us not to trust. We must learn that people and God are not alike. All people are imperfect and even those who try not to hurt others, occasionally do. How can imperfect people love us with perfect love? If they could, we would have no fear. Our fears concerning people being hurt and disappointed by them, would be ended.
Because the emotional pain of rejection, judgment, betrayal, criticism, etc. is very real and devastating, we naturally avoid it once we have experienced it. It seems that people fall into one of two categories, they either withdraw in fear and live lonely lives where they avoid close relationships, or they do what I once did. They want to have relationships, but they can never really develop proper ones because of all their fears.
They end up controlling, manipulating, and being angry a lot. In general, their lives are frustrating, because much of the time, they truly don't know what is wrong. They are reacting out of old wounds rather than acting on the truth of God's Word.
THE CURE FOR THE INSECURE
Insecurity is said to be an epidemic in today's society. There are so many insecure people trying to have relationships with other insecure people. We find a very high percentage of this kind of relationships, which the world calls dysfunctional. This simply means they are not functioning properly.
Most people are raised in dysfunctional homes. They go out into society and continue the dysfunction, and each generation adds to the last one's problems until society becomes increasingly more dysfunctional. There is, however, an answer. His name is Jesus Christ.
When Jesus said in John 14:6, ...I am the Way..., He not only meant that He was the Way to the Father and the Way to heaven, but I believe He also meant that He was the Way out of every wrong and messed-up situation.
If invited, Jesus can get into the middle of dysfunctional lives and make them functional again. He restores, renews, redeems, reconciles, and refreshes. Jesus is "re" everything. The prefix "re" means "to go back again, or to return to the starting place". Our heavenly Father, through Jesus Christ, intends to get us back to the place, where Satan messed things up, and to give us a new beginning.
If we repent, He removes the reproach of the past, gives us a full recompense for our past hurts. Yes, Jesus is the only Way.
Why should Jesus help us in this manner? He does it because He is love because He loves us. He is God's love gift to us. Jesus is the manifestation of Perfect Love. Only Perfect Love can cast out fear. One thing, we need to concentrate on and seek God for, is a revelation about the love He has extended towards us.
Very few people have a deep and abiding revelation concerning the love of God. I believe God wants me to tell you that He loves you very much. That may sound simple, but it is the most powerful thing you can believe. When we know (without doubt) the perfect, complete love that God has for us, it will cause fear to lose its grip on our lives.
LEARNING TO ABIDE IN HIS LOVE
The word, abide means "to dwell in or live". It does not refer to "visiting". It refers to staying or remaining. I don't visit my house; I live in it. We should learn to live in the love of God. I John 4:16 in the Amplified translation brings out the point that we should become conscious and aware of the love God has for us. The knowledge of His love should not be some biblical fact to which we mentally assent, but it should be a daily living reality in our lives. This scripture says we should observe it and experience it.
And we know (understand, recognize, are conscious of, by observation and by experience) and believe (adhere to and put faith in and rely on) the love God cherishes for us. God is love, and he who dwells and continues in God, God dwells and continues in him. (I John 4:16)
I was so desperate for a revelation concerning the love of God, that several years ago I began to keep a journal of the things He did in my life that I believed to be a display of His love. No matter how small they were, I recorded them. This process helped me to become more conscious of His love. I needed to dwell in God's love because I needed a lot of healing. I was insecure and fearful, and I have found out that the love of God is the cure for the insecure.
When people gave me things, I recorded it. When I was shown favor in situations, I recorded it. When God answered prayers and did things for me that I had requested, I recorded it. Many of the things I recorded seemed rather childish, but they were helping me become like the little child Jesus said we should be a child who is trusting, humble, lowly, and loving.
I believe God is showing His love for us daily in many different ways, but because we have not trained ourselves to be "conscious of His love," we miss what He is doing. His love is there, but it is not a reality to us. Therefore, it does not benefit us, as it should.
Paul's prayer for the church, as recorded in the book of Ephesians, indicates how very important it is that we have a deep revelation concerning how much God loves us. Paul could have prayed for anything. He could have prayed for them to have power, to do miracles, to exercise authority over the devil. But Paul prayed for the church to be rooted deeply in God's love.
Paul knew that was the starting point the place from which every point starts the place from which everything else grows. Power, miracles, victory, authority are all based on our being secure in the fact that God loves us.
May Christ through your faith [actually] dwell (settle down, abide, make His permanent home) in your hearts! May you be rooted deep in love and founded securely on love, that you may have the power and be strong to apprehend and grasp with all the saints [God's devoted people, the experience of that love] what is the breadth and length and height and depth [of it]; [that you may really come] to know [practically, through experience for yourselves] the love of Christ, which far surpasses mere knowledge [without experience]; that you may be filled [through all your being] unto all the fullness of God [may have the richest measure of the divine Presence, and become a body wholly filled and flooded with God Himself]! Ephesians 3:17-19
These scriptures make it clear that we need to experience His love not just have head knowledge, but a deep revelation, and that the roots of our being should be "securely" planted in His love.
THE FEAR OF LACK
There are endless varieties of fear, but one of the tormenting fears that many people suffer from is the fear of lack. They fear that their needs will not be met that God will not come through in time.
Hebrews 13:5-6 gives great comfort to those in this situation. Let your character or moral disposition be free from love of money [including greed, avarice, lust, and craving for earthly possessions] and be satisfied with your present [circumstances and with what you have]; for He [God] Himself has said, I will not in any way fail you nor give up nor leave you without support. [I will] not, [I will] not, [I will] not in any degree leave you helpless nor forsake nor let [you] down (relax My hold on you [Assuredly not!]
So we take comfort and are encouraged and confidently and boldly say, The Lord is my Helper; I will not be seized with alarm [I will not fear or dread or be terrified]. What can man do to me?
You may be in a situation right now that you have never been in before. You may be facing new responsibility that you don't know how to handle. You may have needs that are beyond your resources, and the spirit of fear is attacking you and telling you that you are not going to make it. You may feel all alone in your situation, like nobody cares, but God cares about you!
When God says in these scriptures to be satisfied with your present circumstances, He does not mean that you cannot desire change. But we should be content in Jesus, knowing that He has heard our prayers and believing that He will never fail us. We must learn how to enjoy where we are on the way to where we are going.
God is a God of progress. He is never standing still. Even when it seems to us that absolutely nothing is happening in our lives, God is working behind the scene on things that He will manifest at exactly the right time. God is Life and life must flow, otherwise it is no longer life. Dead things stagnate and no longer move, but life is always moving, stirring, making progress.
Beloved, God has a good plan for you, and He will manifest it right on time. Fear not, God is with you and He will never leave you nor forsake you. He will not leave you without support! If you need financial support, He will provide. If it is physical support you need, He will sustain you while you are waiting for your full manifestation of healing. If you need emotional support, He will comfort you with the kind of comfort that only the Holy Spirit can give. He will nourish you and bring you back to a place of strength in every area of your life. God is for you. He is not against you. Satan is against you, but God is for you. The greater One lives in you!
LET NOTHING SEPARATE YOU FROM GOD'S LOVE
Romans 8:35-39 speaks to us about difficult times and how important it is not to allow them to separate us from God's love. I have discovered over the years that His love sustains me in times of great trial and stress. During hard times, Satan works overtime trying to convince us that God does not love us that if He did, either we would not be in this situation, or He would have delivered us by now.
I affirm out loud from my own mouth the truth that God does love me during these attacks of fear. I encourage you to say several times a day with authority, "God loves me!" Don't allow the devil to steal this truth from you.
Ephesians 6 speaks of wearing spiritual armor during demonic attacks. One piece of that armor is the belt of truth. The Amplified Bible states that we are to tighten the belt of truth during attack. That means the truths we have learned from God's Word must be held onto tightly during trials.
Let me close with these scriptures from Romans 8:35-39 and I pray that they will comfort you right now; Who shall ever separate us from Christ's love? Shall suffering and affliction and tribulation? Or calamity and distress? Or persecution or hunger or destitution or peril or sword?
Even as it is written, For Thy sake we are put to death all the day long; we are regarded and counted as sheep for the slaughter. Yet amid all these things we are more than conquerors and gain a surpassing victory through Him Who loved us.
For I am persuaded beyond doubt (am sure) that neither death nor life, nor angels nor principalities, nor things impending and threatening nor things to come, nor powers, nor height nor depth, nor anything else in all creation will be able to separate us from the love of God which is in Christ Jesus our Lord.
As long as you refuse to let anything separate you from God's love, you will have the victory.
You always know that the day will come that your life may be coming to end. For some it comes early, for some in mid life and hopefully for the rest of us when we are old and gray.
During the road of life we take risks, we do dumb things and we make choices because we think we are fearless, a superman of sorts and you only die when you are old. We spend much of our lives in the early years chasing the girls, then getting married and having a family, then years cultivating our careers so we can have the lifestyle that we have always dreamed of and along the way we forget about ourselves and the choices we made not to mention the damage these choices can do to you later in life. They say when you have a life changing situation the best thing is to write it down because you may want to share it with others so here we go.
Over and over we hear and read about all the bad things that can happen to us from alcohol, drugs and smoking. Do we listen? We all know the answer to that for we continue to do bad things to our body. I am just as guilty because I didn
I am a firm believer in planning whatever I want to achieve in my life. Planning (and taking all the actions required to realise the plan) was invaluable in coping with my six lifetime cancer diagnoses.
First diagnosed in 1979, in 2004 I faced my most challenging cancer encounter. For the second time in my life the lymphoma had relapsed to stage 4 (there is no stage 5). Six months of chemotherapy preceded the removal of my spleen, high-dose chemotherapy and a stem-cell transplant.
The combined effects of advanced disease and treatments left me weaker and less mobile than ever before. My willpower, determination and exuberance for life, which had always been my strongest suits, were waning.
My plan for coping included employing a range of psychosocial support measures that had helped me in the past. I drew from my humour library, regularly watching my favourite comedies to lift my spirits. I played music to help me express and manage my emotions. I wrote about what I was experiencing each day to help me examine and vent my feelings.
What helped most though was carrying out a review of my life; looking at whether it was everything I wanted it to be (the cancer notwithstanding). When at your lowest ebb, you need everything possible in your present and future to encourage you to hold on. Reflecting on all areas of my life I realised I needed to change my vocation.
I had never enjoyed some aspects of being a corporate manager. By nature I loved to create and positively influence those around me, while the corporate world is driven by competitiveness and immersed in politics, where values are often surrendered for self-interest. There was a fundamental mismatch between who I was and what I did for a living and I felt remedying this would help my recovery aspirations.
I wrote a compelling vision statement to focus me on a new career and lifestyle: To show people how to live happier and more fulfilling lives. For me this meant doing a number of things. I had long intended to write a book on how to take action to help cope with a cancer battle. I set this project as a high priority.
One thing I had really enjoyed about my corporate job was helping my staff develop and grow as people. I did some research and resolved that I would be able to focus on this for a living as a life and career coach.
I also wanted to give something back in recognition of the support I had received in coping with cancer throughout my life. Like so many people I had benefited greatly from the services of my local Cancer Society, but many others had given freely and generously to help me cope too. I decided that after I had recovered I would find forums to deliver talks about the coping strategies I would subsequently write about in my book Life, Happiness & Cancer.
The motivation and excitement generated by my life-after-cancer planning helped me re-gain my zest for life and emotional strength. I began to cope better with the treatments and my recovery progressed well. By Christmas 2004 I was back at home in full remission. My energies returned steadily along with my hair, as I put my plan into action full of enthusiasm for life.
That was over two years ago. I found happiness and fulfilment in my new activities. I wrote and published my book, which became and remains a bestseller in New Zealand. I trained to become a life and career coach and established my own business. I was even discovered (as they say) while promoting my book on television, and became the resident life coach on a morning TV show. And as Christmas 2006 arrived I had delivered my Life, Happiness & Cancer presentation to over 1,500 people at 31 forums.
But my ultimate joy came in November 2006 when I learned my wife Gillian was pregnant with our first child. This too, we planned!
The great English poet WH Auden defined cancer as a foiled creative fire. For me, reigniting my own fire by planning a new lifestyle and career helped me cope with and eventually overcome cancer, and to establish an even better life than before.
Phil Kerslake lives in New Zealand, is a six-time survivor of different lymphomas across four decades and the author of the 2006 book Life, Happiness & Cancer: Survive with Action and Attitude! For more information about Phil, his book and presentations to cancer support conferences visit his website www.lifepaths.co.nz.
When it comes to fighting cancer, many people seem to want to go it alone. For some reason we view the cancer struggle as a private affair and often hold at arms length people who might otherwise have helped us immensely. I know because I was certainly one of those people in 1979 when I was first diagnosed with a lymphoma as a teenager. In 1987 when I was admitted to Wellington hospital with widespread, advanced disease I was still of the mind that the business of beating my cancer was mine alone, making it clear to even my closest friends that they were to leave me alone until I surfaced again, with full health restored.
You can therefore imagine my response when invited to attend cancer support groups back then. I avoided them like the plague. I was clearly a loner when it came to facing my health problems but on top of that I had a terribly negative image of cancer support groups. I had this preconception of mutual moaning forums. I also very uncharitably believed people who joined a group were not strong enough to face their battles alone. I saw myself as stronger than that.
I was intrigued then in the early 1990s when, with an early notion of writing a book on boosting quality of life and maybe even the odds of beating cancer I came across screeds of material lauding cancer support groups for their therapeutic benefits. My reading suggested a safe, positive and unpretentious environment where participants could express their feelings but also simply share the nuances and peculiarities of the cancer experience with people in the same predicament as they.
First and foremost, the literature said, a support group enabled you to express yourself in a safe and truly understanding forum. An important benefit of a group was said to be that it allowed the cancer patient to regain some sense of control in their lives after a period since their diagnosis where they had quite possibly felt out of control in every sense. Amongst other people facing similar challenges life crises are put into better perspective. I knew as a cancer survivor that when diagnosed with the disease you can and often do feel like the only one afflicted.
In 1994 I received another recurrence scare. This time my recurrence was localized and some weeks of radiotherapy cleared the disease. However for me that didnt lessen the usual associated fears, reflections and element of post-treatment depression. I decided to change my coping pattern and took steps to link up with a support group for a period of time. What I experienced reflected all the good things Id read about cancer support groups and more. I found the group to be a strong set of individuals. While we all had our fears about the present and the future, there was a dignity and resilience in each person that I admired greatly.
People didnt complain or whine as I had imagined those years before. Each person brought their own coping approaches to the table and I found that I learned from them. I became more open, more giving and more sharing. I actually believe that I became a better person for the experience. When I had my latest recurrence from late 2003 through all of 2004, I found myself with an entirely different coping style which served me well. This time I was open to all my friends and family in the experience and I know that the reciprocated love, caring and openness made a difference for me. It may have been the difference in my recovery.
Even the most individualistic of us cannot be Islands unto ourselves. Even the strongest and most private of us needs to open ourselves up to others. Being able to share our experiences during a cancer battle helps us achieve a more settled state of mind which underpins our recovery aspirations. Now, as a 47 year old man with 28 years experience with cancer my first advice to the newly diagnosed is to find a cancer support group and allow the collective dignity, strength and humanity found there to steady and ground them for the difficult experience ahead.
Phil Kerslake is a New Zealand six-time cancer survivor, speaker to cancer support forums worldwide and author of the 2006 book: Life, Happiness & Cancer: Survive with Action and Attitude! For more about Phil, his book and speaking services visit his website www.lifepaths.co.nz.
Functional profiling with cell culture assays for targeted drug therapy
Recent findings presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in Orlando, Florida concluded that Functional Profiling (whole cell profiling) with cell culture assays is relevant for the study of both "conventional" and "targeted" antineoplastic drug agents.
Cell Culture Assays with "cell-death" endpoints can show disease-specific drug activity, are useful clinical and research tools for "conventional" and "targeted" drugs, and provide unique information complementary to that provided by "molecular" tests. There have been more than 25 peer-reviewed publicatons showing significant correlations between cell-death assay results and patient response and survival.
The Whole Cell Profiling technique is a cell-death endpoint assay in which drug effect upon cancer cells is visualized directly. Photomicrographs of actual tumor cells sometime show that the exact same identical individual culture well, shows some clusters have taken up vast amounts of a drug, while right next door, clusters of the same size, same appearance, same everything haven't taken up any of the drug.
So it doesn't matter if there is a "target" molecule (protein or receptor) 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. The advantage of the Whole Cell Profiling technique is that it can show this in the "population" of cells.
The Whole Cell Profiling technique makes the statistically significant association between prospectively reported test results and patient survival. It can correlate test results which are obtained in the lab and reported to physicians prior to patient treatment, with significantly longer or shorter overall patient survival depending upon whether the drug was found to be effective or ineffective at killing the patient's tumor cells in the laboratory.
This could help solve the problem of knowing which patients can tolerate costly, new treatments and their harmful side-effects. These "smart" drugs are a really exciting element of cancer medicine, but do not work for everyone, and a test to determine the efficacy of these drugs in a patient could be the first crucial step in personalizing treatment to the individual.
Functional profiling (FP) with cell culture assays for targeted drug therapy.
Sub-category: Translational research
Category: Colon and Rectum
Meeting: 2007 Gastrointestinal Cancers Symposium
Abstract No: 440
Author(s): L. M. Weisenthal
Abstract: Introduction: We studied the relevance of FP for standard and targeted drugs.
Methods: Drugs were tested against fresh human tumor microclusters, with 96 hr drug exposures and multiple FP endpoints (MTT, DISC, resazurin, and/or ATP).
Results: In 65 previously chemonaive stage 4 colon cancer patients, those with FP assays showing 5FU results in the most resistant tertile had inferior overall survival, compared to pts without 5FU resistance (303 days vs. 686 days, H.R. 2.1, 95% C.I. 1.2 - 5.0, P2=0.011). In subset analysis restricted only to 53 pts who subsequently died (eliminating potential surgical cures), the respective results were 292 vs 493 days, HR 1.5 - 6.9, P2=0.0021. We applied FP to test targeted agents, including gefitinib, erlotinib, sunitinib, sorafenib, and bevacizumab. Gefitinib was tested against > 700 fresh tumor specimens; we reported striking correlations between gefitinib activity and overall pt survival in non-small lung cancer (2006 ASCO Annu Mtg, Abst 17117). Gefitinib and erlotinib are moderately cross resistant (R2=0.48, n paired comparisons=190). Gefitinib/sunitinib (R2=0.20, n=46) and erlotinib/sunitinib (R2=0.12, n=44) are largely non-cross resistant. We also developed a new microvascular viability assay (MVVA) to test microvascular cells present in tumor clusters. In the MVVA, bevacizumab was tested in 81 fresh tumor specimens (including 15 GI). Bevacizumab was nontoxic to the tumor cells, but often strikingly toxic to microvascular cells present within the same tumor clusters. Grading on a 0-4 scale, there was absent (Gr 0) effect in 23 specimens, weak (Gr 1-2) effect in 28, and a strong (Gr 3-4) effect in 26. In contrast to bevacizumab, neither sunitinib (n=87) nor sorafenib (n=20) showed selective effects against microvascular cells compared to tumor cells.
Conclusions: We cannot rule out a cytostatic effect of sunitinib or sorafenib on tumor microvascular cells. However, our results imply that the antitumor effects of bevacizumab are predominately mediated through antimicrovascular effects, while effects of sunitinib and sorafenib may be mediated largely through tumor cell apoptosis. We conclude that FP is relevant for the study of both traditional and targeted antineoplastic agents.
The high recurrence after surical resection of HCC is a major therapeutic challenge. This adjuvant treatment into the hepatic artery has been proposed by Lau WY, Leung TW, et al in previous studies. In 2005, treatment was in phase III clinical trials in Singapore.
As we enter the era of "personalized" medicine, it is time to take a fresh look at how we evaluate treatments for cancer patients. More emphasis should be put on matching treatment to the patient. 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.
Findings presented at the 41st Annual Meeting of the European Society for Clinical Investigation in Uppsala, Sweden, April 18, 2007, concluded that "functional profiling" with cell culture assays is relevant for the study of both "conventional" and "targeted" anti-neoplastic drug agents (anti-tumor and anti-angiogenic activity of Iressa, Tarceva, Sutent, Nexavar, and Avastin in primary cultures of "fresh" human tumors).
Cell Culture Assays with "cell-death" endpoints can show disease-specific drug activity, are useful clinical and research tools for "conventional" and "targeted" drugs, and provide unique information complementary to that provided by "molecular" tests. There have been more than 25 peer-reviewed publications showing significant correlations between cell-death assay results and patient response and survival.
Many patients are treated not only with a "targeted" therapy drug like Tarceva, Avastin, or Iressa, but with a combination of chemotherapy drugs. Therefore, existing DNA or RNA sequences or expression of individual proteins often examine only one compenent of a much larger, interactive process. The oncologist might need to administer several chemotherapy drugs at varying doses because tumor cells express survival factors with a wide degree of individual cell variability.
There is a tactic of using biopsied cells to predict which cancer treatments will work best for the patient, by taking pieces of live "fresh" tumor tissue, applying different chemotherapy treatments to it, and examining the results to see which drug or combination of drugs does the best job killing the tumor cells. A cell culture assay test with "functional profiling," using a cell-death endpoint, can help see what treatments will not have the best opportunity of being successful (resistant) and identify drugs that have the best opportunity of being successful (sensitive).
"Funtional profiling" measures the response of the tumor cells to drug exposure. Following this exposure, they measure both cell metabolism and cell morphology. The integrated effect of the drugs on the whole cell, resulting in a cellular response to the drug, measuring the interaction of the entire genome. No matter which genes are being affected, "functional profiling" is measuring them through the surrogate of measuring if the cell is alive or dead.
For example, the epidermal growth factor receptor (EGFR) is a protein on the surface of a cell. EGFR-inhibiting drugs certainly do target specific genes, but even knowing what genes the drugs target doesn't tell you the whole story. Both Iressa and Tarceva target EGFR protein-tyrosine kinases. But all the EGFR mutation or amplificaton studies can tell us is whether or not the cells are potentially susceptible to this mechanism of attack. They don't tell you if Iressa is better or worse than Tarceva or other drugs which may target this. There are differences. The drugs have to get inside the cells in order to target anything. So, in different tumors, either Iressa or Tarceva might get in better or worse than the other. And the drugs may also be inactivated at different rates, also contributing to sensitivity versus resistance.
As an example of this testing, researchers have tested how well a pancreatic cancer patient can be treated successfully with a combination of drugs commonly used to fight lung, pancreatic, breast, and colorectal cancers. The pre-test can report prospectively to a physician specifically which chemotherapy agent would benefit a cancer patient. Drug sensitivity profiles differ significantly among cancer patients even when diagnosed with the same cancer.
The "funtional profiling" technique makes the statistically significant association between prospectively reported test results and patient survival. It can correlate test results that are obtained in the lab and reported to physicians prior to patient treatment, with significantly longer or shorter overall patient survival depending upon whether the drug was found to be effective or ineffective at killing the patient's tumor cells in the laboratory.
This could help solve the problem of knowing which patients can tolerate costly new treatments and their harmful side effects. These "smart" drugs are a really exciting element of cancer medicine, but do not work for everyone, and a test to determine the efficacy of these drugs in a patient could be the first crucial step in personalizing treatment to the individual.