My Beneficiaries

“After more than 10 years I can safely say I do not have schizophrenia but ESP, all the doctors mis-diagnosed my condition and make me suffer so much problems. SCREW the government. I have Buddha Ears which I can listen to many conversations in the world, so I do not need your feedback. Am I entitled to claim compensation? Definitely YES. Then who will be my beneficiaries?”. – Contributed by Oogle.

My Beneficiaries

I hereby authorised all my below charity organisations to use any of my works on my websites, including research of knowledge to raise money for causes relating to solving Hunger & Poverty, Diseases or Inequality. If any requires the issue of licenses regarding to patents, please highlight the patents required, including the location where the patent is exercised, and the parties involved. Please note for commercial purposes, licenses cannot be issued without costs but I will consider FREELY for NON PROFIT. I will even consider working on collaboration with partners to bring all my technologies for commercialisation. If you need a copy of my terms and conditions, you can email to

Ten years back I have invented the ability to hack into any black box with inputs to study the outputs, and also the ability to find any answers closest to the solution to any topic, re-assembling it to create my own technologies, now I have re-invented every technology that intends to rob and steal, turning the entire market into a perfect market, I have mastered almost every industry, and now channelling my knowledge to help mankind find success, against all those who only want power, domination and destruction. I even have the ability to find out the future potential of any product or technology, creating a road map of everything in every industry that will have a 100% potential of success, maximising ROI and saving scarce resources. I even have perfected visualisation with my mind in 4D, solving a rubic cube puzzle four different faces at the same time, playing multiple sets of chess but has yet try to solve multiple rubic cube puzzles all at the same time but I will achieve it soon. So many people had made very good money from all my websites, without the governments fooling around, I could easily raise hundreds of billions for all my non-profit projects.

Our Services are ;

IT Consultancy
– Hardware/Software for PCs/Servers
– Multiple OS including Servers
– Desktop/Servers/Network Security
– Firewalls/Antivirus
– Search Engine Expert
– Database/Mining/Analysis/Insights
– Customisation of any hardware/software
– Inventor of ;
3D Search Engine
Next Generation Internet
Intelligent Matrix Routing
Intelligent OS/Programming
Merging Extended WiFi/TD-SCDMA/Any Networks
New OLED player/Screen Display Technology
Online Numbers/Video/Voice Networks
HFT Systems
Mobile Devices/Network Technology
Economics/Financial Consultancy
– The New Economy
– How to avoid Destructive Competition
– Fixing everything for A Perfect Economy
Business Consultancy
– Solve any problems or processes
– Goal planning with results
– Maximise ROI/Cash flow
– Fund management advice
– How to ensure success
– Raising Funds with Goals
– Solving any problems
– Micro Credit for Social Enterprises(Entrepreneurs)
– Solving Diseases
– Creating Jobs for everyone

Elim Church AOG(Singapore)
Kwong Wai Shiu Hospital
Wikipedia Foundation
Salvation Army
MacDonald’s Charities
United Nations
BRICS Development Bank

She will die before LKY and no-one will bury her

She will die before LKY and no-one will bury her

1) My Mom is linked to LKY’s Lee, Tay and Lim Family.
2) My ex-wife family are distant relatives of LKY.
3) That is the reason why my mom can get so many people to attack, control me.
4) That is the reason why the Singapore and US government is involved.
5) There is no way anyone can control me.
6) I will never give in to my family.
7) I will disown everyone in my family.
8) I am capable of achieving anything on my own without my family.

I accused my mom of masterminding everything, as I can easily read all her intentions
1) To prevent me from leaving Singapore.
2) To prevent me from getting an income by messing with my bank account.
3) To prevent me from selling any of my inventions as I am not able to enforce copyright on my websites.
4) She collaborated with everyone, Government of Singapore and US to give me hardship with so many problems so that she could steal and rob me.
5) She try to show everyone I am a bum and a mentally retarded person but I have proven otherwise. It took me more than 10 years of every night’s work to achieve it.
6) There were so many incidents where all of my work, money and success were taken away from me. I now want compensation and revenge.
7) She is afraid I get married so my wife will get all my inheritence so she also meddle with my love life.
8) Everything in my life she wants total control so she controls all my money, but is she capable?NO, I am 1000 times more capable and smarter than her. Money she stole from me can only create even more corruption, everyone will also rob her.
9) I am even smarter, without any rewards I will lock everything up forever.
10)Nothing I will leave for my family, everything I donate to the United Nation, 100% of my inheritence.

I hate it when the government tries to be funny to brainwash security sensitive personnel who are exposed to technologies that can commit fraud, I am already an expert in everything, and I do not believe in ethical hacking, I can create so much money there is no need for me to commit crime, stop all nonsense or I will create more nonsense for everybody. Brainwashing does not work on me. Now I want compensation and damages for all my sufferings.
I have made 3 police reports on the mistreatment by my mom who abuse me and I have already sealed the case to disown my entire family for robbing me of my success and trying to control my money and everything. I will drag their reputation through the mud as I will not conform to anything.
There is nothing good she does without benefits. I caught her taking money from a stall holder in changi village, and also from a software programmer with two nightclub girls at macdonalds in the middle of the night celebrating after stealing from my inventions. She will ask you to be at some place to show your face so that she can get money from the owner, she is living off me and try to prove to me she can make money, even my doctor I see she wants to make money, and get free treatment for lasik eye surgery, SHIT AND FUCK HER! I really don’t give a damn if anybody makes money from my websites, but if you think you can control me or control my income, I will show you how you are going to lose your pants when you challenge me, I will use what you use to run circles round everybody, and nobody still get any results after 100 years.

– Contributed by Oogle.

One day, there will be no rejection for transplanted cells

“We are coming to the age where every part of our body can be transplanted except the brain, where all kinds of cells can be cultured in the lab, it is the study of the body immunity system that will open the doors to prevent rejection.” – Contributed by Oogle.
Dec. 17, 2012 — How can the immune system be reprogrammed once it goes on the attack against its own body? EPFL scientists retrained T-cells involved in type I diabetes, a common autoimmune disease. Using a modified protein, they precisely targeted the white blood cells (T-lymphocytes, or T-cells) that were attacking pancreatic cells and causing the disease. When tested on laboratory mice, the therapy eliminated all signs of the pathology. This same method could be a very promising avenue for treating multiple sclerosis as well. The scientists have just launched a start-up company, Anokion SA, on the Lausanne campus, and are planning to conduct clinical trials within the next two years.

Their discovery has been published in the journal PNAS (Proceedings of the National Academy of Science).
To retrain the rebellious white blood cells, the researchers began with a relatively simple observation: every day, thousands of our cells die. Each time a cell bites the dust, it sends out a message to the immune system. If the death is caused by trauma, such as an inflammation, the message tends to stimulate white blood cells to become aggressive. But if the cell dies a programmed death at the end of its natural life cycle, it sends out a soothing signal.

In the human body there is a type of cell that dies off en masse, on the order of 200 billion per day — red blood cells. Each of these programmed deaths sends a soothing message to the immune system. The scientists took advantage of this situation, and attached the pancreatic protein targeted by T-cells in type I diabetes to red blood cells.

“Our idea was that by associating the protein under attack to a soothing event, like the programmed death of red blood cells, we would reduce the intensity of the immune response,” explains Jeffrey Hubbell, co-author of the study. To do this, the researchers had to do some clever bioengineering and equip the protein with a tiny, molecular scale hook, that is able to attach itself to a red blood cell. Billions of these were manufactured and then simply injected into the body.

Complete eradication of diabetes symptoms

As these billions of red blood cells died their programmed death, they released two signals: the artificially attached pancreatic protein, and the soothing signal. The association of these two elements, like Pavlov’s dog, who associates the ringing of a bell with a good or bad outcome, essentially retrained the T lymphocytes to stop attacking the pancreatic cells. “It was a total success. We were able to eliminate the immune response in type I diabetes in mice,” explains Hubbell.

Minimizing risks and side effects

Co-author Stephan Kontos adds that the great advantage of this approach is its extreme precision. “Our method carries very little risk and shouldn’t introduce significant side effects, in the sense that we are not targeting the entire immune system, but just the specific kind of T-cells involved in the disease.”

The scientists are planning to conduct clinical trials in 2014, at the earliest. To demonstrate the potential of their method, they plan to first test applications that would counteract the immune response to a drug known for its effectiveness against gout. “We chose to begin with this application before we tackled diabetes or multiple sclerosis, since we knew and were in control of all the parameters,” explains Hubbell.

Currently, the researchers are also testing the potential of this method in treating multiple sclerosis. In this disease, T-cells destroy myelin cells, which form a protective sheath around nerve fibers. They are also studying the potential of their method with another kind of white blood cell, B-lymphocytes, that are involved in many other autoimmune diseases.

Earthquake resistant structures using 3D designs where every stone of foundation is different

Dry-stone walls control (The rebuilding of Japan Earthquake and Tsunami regions)

People of Inca civilization were masters of the polished ‘dry-stone walls’, called ashlar, where blocks of stone were cut to fit together tightly without any mortar. The Incas were among the best stonemasons the world has ever seen,[22] and many junctions in their masonry were so perfect that even blades of grass could not fit between the stones.

Peru is a highly seismic land, and for centuries the mortar-free construction proved to be apparently more earthquake-resistant than using mortar. The stones of the dry-stone walls built by the Incas could move slightly and resettle without the walls collapsing, a passive structural control technique employing both the principle of energy dissipation and that of suppressing resonant amplifications.[23]

By studying the three movements of earthquakes (up /down)(left/right)(diagonal up/down) and the intensity of earthquakes on different types of bricks, I can even find out the centre of gravity of every brick, and redesign the entire brick wall using 3D design by using algorithms to calculate for unique bricks that form together that is so strong it can withstand a 10 digit scale earthquake, but the binding material cannot be cement, it will be locked together by steel devices that link the centre of gravity together of all blocks that is so strong it cannot be dislodged. – Contributed by Oogle

Chemical imbalances in the brain is the onset of mental illness

“There is no mental illness drugs in the market today without side effects, does all these drugs actually solved the exact chemical imbalances in the brain, or cause more problems. There will be advances in MRI technology, where you can see the color coded contents of nutrients, flowing in a brain wiring scan.” – Contributed by Oogle.

Chemical imbalance is one hypothesis about the cause of mental illness. Other causes that are debated include psychological and social causes.

The basic concept is that neurotransmitter imbalances within the brain are the main causes of psychiatric conditions and that these conditions can be improved with medication which corrects these imbalances. The phrase originated from the scientific study of brain chemistry. In the 1950s the monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants were accidentally discovered to be effective in the treatment of depression.[1]

These findings and other supporting evidence led scientist Joseph J. Schildkraut (1934–2006) to publish his paper called “The Catecholamine Hypothesis of Affective Disorders” in 1965.[2][3] Schildkraut associated low levels of neurotransmitters with depression.

Research into other mental illnesses such as schizophrenia also found that too much activity of certain neurotransmitters such as dopamine was correlated to these disorders. In the scientific community this hypothesis has been referred to as the “Monoamine hypothesis”. This hypothesis has been a major focus of research in the fields pathophysiology and pharmacotherapy for over 25 years[4] and led to the development of new classes of drugs such as SSRIs (selective-serotonin reuptake inhibitors).[5]

Stroke when occurs destroy brain cells that inhabit the movement of certain parts of our body, when even if the chemical imbalance is rectified, the learning process needs to start from scratch. But once my research is completed, it may be possible to duplicate these cells that have been destroyed with healthy cells that may one day restore the movements of stroke victims.

– Contributed by Oogle.

P/S : I do not have any vested interests in writing all these articles, neither am I paid by anyone, I am just concern about all these rubbish they(Drug Companies) subject young children to take un-necessary anti-depression drugs which may harm them for life.

Targeted Cancer Therapies

  • Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules involved in tumor growth and progression.
  • Because scientists call these specific molecules “molecular targets,” therapies that interfere with them are sometimes called “molecularly targeted drugs,” “molecularly targeted therapies,” or other similar names.
  • Targeted cancer therapies that have been approved for use in specific cancers include drugs that interfere with cell growth signaling or tumor blood vessel development, promote the specific death of cancer cells, stimulate the immune system to destroy specific cancer cells, and deliver toxic drugs to cancer cells.
  1. What are targeted cancer therapies?Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules involved in tumor growth and progression. Because scientists often call these molecules “molecular targets,” targeted cancer therapies are sometimes called “molecularly targeted drugs,” “molecularly  targeted therapies,” or other similar names. By focusing on molecular and cellular changes that are specific to cancer, targeted cancer therapies may be more effective than other types of treatment, including chemotherapy and radiotherapy, and less harmful to normal cells.

    Many targeted cancer therapies have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of specific types of cancer (see details in Questions 4 and 5). Others are being studied in clinical trials (research studies with people), and many more are in preclinical testing (research studies with animals).

    Targeted cancer therapies are being studied for use alone, in combination with other targeted therapies, and in combination with other cancer treatments, such as chemotherapy.

  2. How do targeted cancer therapies work?Targeted cancer therapies interfere with cancer cell division (proliferation) and spread in different ways. Many of these therapies focus on proteins that are involved in cell signaling pathways, which form a complex communication system that governs basic cellular functions and activities, such as cell division, cell movement, cell responses to specific external stimuli, and even cell death. By blocking signals that tell cancer cells to grow and divide uncontrollably, targeted cancer therapies can help stop cancer progression and may induce cancer cell death through a process known as apoptosis. Other targeted therapies can cause cancer cell death directly, by specifically inducing apoptosis, or indirectly, by stimulating the immune system to recognize and destroy cancer cells and/or by delivering toxic substances directly to the cancer cells.

    The development of targeted therapies, therefore, requires the identification of good targets—that is, targets that are known to play a key role in cancer cell growth and survival. (It is for this reason that targeted therapies are often referred to as the product of “rational drug design.”)

    For example, most cases of chronic myeloid leukemia (CML) are caused by the formation of a gene called BCR-ABL. This gene is formed when pieces of chromosome 9 and chromosome 22 break off and trade places. One of the changed chromosomes resulting from this switch contains part of the ABL gene from chromosome 9 fused to part of the BCR gene from chromosome 22. The protein normally produced by the ABL gene (Abl) is a signaling molecule that plays an important role in controlling cell proliferation and usually must interact with other signaling molecules to be active. However, Abl signaling is always active in the protein (Bcr-Abl) produced by the BCR-ABL fusion gene. This activity promotes the continuous proliferation of CML cells. Therefore, Bcr-Abl represents a good molecule to target.

  3. How are targeted therapies developed?Once a target has been identified, a therapy must be developed. Most targeted therapies are either small-molecule drugs or monoclonal antibodies. Small-molecule drugs are typically able to diffuse into cells and can act on targets that are found inside the cell. Most monoclonal antibodies cannot penetrate the cell’s plasma membrane and are directed against targets that are outside cells or on the cell surface.

    Candidates for small-molecule drugs are usually identified in studies known as drug screens—laboratory tests that look at the effects of thousands of test compounds on a specific target, such as Bcr-Abl. The best candidates are then chemically modified to produce numerous closely related versions, and these are tested to identify the most effective and specific drugs.

    Monoclonal antibodies, by contrast, are prepared first by immunizing animals (typically mice) with purified target molecules. The immunized animals will make many different types of antibodies against the target. Next, spleen cells, each of which makes only one type of antibody, are collected from the immunized animals and fused with myeloma cells. Cloning of these fused cells generates cultures of cells that produce large amounts of a single type of antibody, known as a monoclonal antibody. These antibodies are then tested to find the ones that react best with the target.

    Before they can be used in humans, monoclonal antibodies are “humanized” by replacing as much of the animal portion of the antibody as possible with human portions. This is done through genetic engineering. Humanizing is necessary to prevent the human immune system from recognizing the monoclonal antibody as “foreign” and destroying it before it has a chance to interact with and inactivate its target molecule.

  4. What was the first target for targeted cancer therapy?The first molecular target for targeted cancer therapy was the cellular receptor for the female sex hormone estrogen, which many breast cancers require for growth. When estrogen binds to the estrogen receptor (ER) inside cells, the resulting hormone-receptor complex activates the expression of specific genes, including genes involved in cell growth and proliferation. Research has shown that interfering with estrogen’s ability to stimulate the growth of breast cancer cells that have these receptors (ER-positive breast cancer cells) is an effective treatment approach.

    Several drugs that interfere with estrogen binding to the ER have been approved by the FDA for the treatment of ER-positive breast cancer. Drugs called selective estrogen receptor modulators (SERMs), including tamoxifen and toremifene (Fareston®), bind to the ER and prevent estrogen binding. Another drug, fulvestrant (Faslodex®), binds to the ER and promotes its destruction, thereby reducing ER levels inside cells.

    Aromatase inhibitors (AIs) are another class of targeted drugs that interfere with estrogen’s ability to promote the growth of ER-positive breast cancers. The enzyme aromatase is necessary to produce estrogen in the body. Blocking the activity of aromatase lowers estrogen levels and inhibits the growth of cancers that need estrogen to grow. AIs are used mostly in women who have reached menopause because the ovaries of premenopausal women can produce enough aromatase to override the inhibition. Three AIs have been approved by the FDA for the treatment of ER-positive breast cancer: Anastrozole (Arimidex®), exemestane (Aromasin®), and letrozole (Femara®).

  5. What are some other targeted therapies?Targeted cancer therapies have been developed that interfere with a variety of other cellular processes. FDA-approved drugs that target these processes are listed below.

    Some targeted therapies block specific enzymes and growth factor receptors involved in cancer cell proliferation. These drugs are sometimes called signal transduction inhibitors.

    • Imatinib mesylate (Gleevec®) is approved to treat gastrointestinal stromal tumor (a rare cancer of the gastrointestinal tract), certain kinds of leukemia, dermatofibrosarcoma protuberans, myelodysplastic/myeloproliferative disorders, and systemic mastocytosis. The drug targets several members of a class of proteins called tyrosine kinase enzymes that participate in signal transduction. These enzymes are overactive in some cancers, leading to uncontrolled growth. It is a small-molecule drug, which means that it can pass through cell membranes and reach targets inside the cell.
    • Dasatinib (Sprycel®) is approved to treat some patients with CML or acute lymphoblastic leukemia. The drug is a small-molecule inhibitor of several tyrosine kinase enzymes.
    • Nilotinib (Tasigna®) is approved to treat some patients with CML. The drug is another small-molecule tyrosine kinase inhibitor.
    • Bosutinib (Bosulif®) is also approved to treat some patients with CML. The drug is a small-molecule tyrosine kinase inhibitor.
    • Trastuzumab (Herceptin®) is approved to treat certain types of breast cancer as well as some types of gastric or gastroesophageal junction adenocarcinoma. The therapy is a monoclonal antibody that binds to the human epidermal growth factor receptor 2 (HER-2). HER-2, a receptor with tyrosine kinase activity, is expressed at high levels in some breast cancers and also some other types of cancer. The mechanism by which trastuzumab acts is not completely understood, but one likely possibility is that it prevents HER-2 from sending growth-promoting signals. Trastuzumab may have other effects as well, such as inducing the immune system to attack cells that express high levels of HER-2.
    • Pertuzumab (Perjeta™) is approved to be used in combination with trastuzumab and docetaxel to treat metastatic breast cancer that expresses HER-2 and has not been treated with chemotherapy or a HER-2-directed therapy. Pertuzumab is a monoclonal antibody that binds to HER-2 at a region distinct from trastuzumab. This region allows HER-2 to interact with other receptors, such as the epidermal growth factor receptor (EGFR), to send growth-promoting signals. The drug likely prevents HER-2 from sending growth signals and induces the immune system to attack HER-2-expressing cells.
    • Lapatinib (Tykerb®) is approved for the treatment of certain types of advanced or metastatic breast cancer. This small-molecule drug inhibits several tyrosine kinases, including the tyrosine kinase activity of HER-2. Lapatinib treatment prevents HER-2 signals from activating cell growth.
    • Gefitinib (Iressa®) is approved to treat patients with advanced non-small cell lung cancer. This small-molecule drug is restricted to use in patients who, in the opinion of their treating physician, are currently benefiting, or have previously benefited, from gefitinib treatment. Gefitinib inhibits the tyrosine kinase activity of EGFR, which is overproduced by many types of cancer cells.
    • Erlotinib (Tarceva®) is approved to treat metastatic non-small cell lung cancer and pancreatic cancer that cannot be removed by surgery or has metastasized. This small-molecule drug inhibits the tyrosine kinase activity of EGFR.
    • Cetuximab (Erbitux®) is a monoclonal antibody that is approved to treat some patients with squamous cell carcinoma of the head and neck or colorectal cancer. The drug binds to the external portion of EGFR, thereby preventing the receptor from being activated by growth signals, which may inhibit signal transduction and lead to antiproliferative effects.
    • Panitumumab (Vectibix®) is approved to treat some patients with metastatic colon cancer. This monoclonal antibody attaches to EGFR and prevents it from sending growth signals.
    • Temsirolimus (Torisel®) is approved to treat patients with advanced renal cell carcinoma. This small-molecule drug is a specific inhibitor of a serine/threonine kinase called mTOR that is activated in tumor cells and stimulates their growth and proliferation.
    • Everolimus (Afinitor®) is approved to treat patients with advanced kidney cancer whose disease has progressed after treatment with other therapies, patients with subependymal giant cell astrocytoma who also have tuberous sclerosis and are unable to have surgery, some patients with advanced breast cancer, or patients with pancreatic neuroendocrine tumors that cannot be removed by surgery, are locally advanced, or have metastasized. This small-molecule drug binds to a protein called immunophilin FK binding protein-12, forming a complex that in turn binds to and inhibits the mTOR kinase.
    • Vandetanib (Caprelsa®) is approved to treat patients with metastatic medullary thyroid cancer who are ineligible for surgery. This small-molecule drug binds to and blocks the growth-promoting activity of several tyrosine kinase enzymes, including EGFR, several receptors for vascular endothelial growth factor receptor (VEGF), and RET.
    • Vemurafenib (Zelboraf®) is approved to treat certain patients with inoperable or metastatic melanoma. This small-molecule drug blocks the activity of a permanently activated mutant form of the serine/threonine kinase BRAF (known as BRAF V600E).
    • Crizotinib (Xalkori®) is approved to treat certain patients with locally advanced or metastatic non-small cell lung cancer. This small-molecule drug inhibits the tyrosine kinase activity of a fusion protein called EML4-ALK, resulting in decreased tumor cell growth, migration, and invasiveness.

    Other targeted therapies modify the function of proteins that regulate gene expression and other cellular functions.

    • Vorinostat (Zolinza®) is approved to treat cutaneous T-cell lymphoma (CTCL) that has persisted, progressed, or recurred during or after treatment with other medicines. This small-molecule drug inhibits the activity of a group of enzymes called histone deacetylases (HDACs), which remove small chemical groups called acetyl groups from many different proteins, including proteins that regulate gene expression. By altering the acetylation of these proteins, HDAC inhibitors can induce tumor cell differentiation, cell cycle arrest, and apoptosis.
    • Romidepsin (Istodax®) is approved to treat CTCL in patients who have received at least one prior systemic therapy. This small-molecule drug inhibits members of one class of HDACs and induces tumor cell apoptosis.
    • Bexarotene (Targretin®) is approved to treat some patients with CTCL. This drug belongs to a class of compounds called retinoids, which are chemically related to vitamin A. Bexarotene binds selectively to, and thereby activates, retinoid X receptors. Once activated, these nuclear proteins act in concert with retinoic acid receptors to regulate the expression of genes that control cell growth, differentiation, survival, and death.
    • Alitretinoin (Panretin®) is approved to treat cutaneous lesions in patients with AIDS-related Kaposi sarcoma. This retinoid binds to both retinoic acid receptors and retinoid X receptors.
    • Tretinoin (Vesanoid®) is approved for the induction of remission in certain patients with acute promyelocytic leukemia. This retinoid binds to and thereby activates retinoic acid receptors.

    Some targeted therapies induce cancer cells to undergo apoptosis (cell death).

    • Bortezomib (Velcade®) is approved to treat some patients with multiple myeloma and some patients with mantle cell lymphoma. Bortezomib causes cancer cells to die by interfering with the action of a large cellular structure called the proteasome, which controls the degradation of many proteins that regulate cell proliferation. Drugs that block this process are called proteasome inhibitors. Proteasome inhibitors affect normal cells, too, but to a lesser extent.
    • Carfilzomib (Kyprolis™) is approved to treat some patients with multiple myeloma whose disease has progressed after treatment with bortezomib. Carfilzomib is another proteasome inhibitor.
    • Pralatrexate (Folotyn®) is approved for the treatment of some patients with peripheral T-cell lymphoma. Pralatrexate is an antifolate, which is a type of molecule that interferes with DNA synthesis. Other antifolates, such as methotrexate, are not considered targeted therapies because they interfere with DNA synthesis in all dividing cells. However, pralatrexate appears to selectively accumulate in cells that express RFC-1, a protein that may be overexpressed by some cancer cells.

    Other targeted therapies block the growth of blood vessels to tumors (angiogenesis). To grow beyond a certain size, tumors must obtain a blood supply to get the oxygen and nutrients needed for continued growth. Treatments that interfere with angiogenesis may block tumor growth.

    • Bevacizumab (Avastin®) is a monoclonal antibody that is approved for the treatment of glioblastoma. The therapy is also approved to treat some patients with non-small cell lung cancer, metastatic colorectal cancer, and metastatic kidney cancer. Bevacizumab binds to VEGF and prevents it from interacting with receptors on endothelial cells, blocking a step that is necessary for the initiation of new blood vessel growth.
    • Ziv-aflibercept (Zaltrap®) is a recombinant fusion protein that is approved for the treatment of some patients with metastatic colorectal cancer. Ziv-aflibercept consists of portions of two different VEGF receptors fused to a portion of an immune protein. By binding to VEGF, ziv-aflibercept prevents it from interacting with receptors on endothelial cells, thereby blocking the growth and development of new blood vessels.
    • Sorafenib (Nexavar®) is a small-molecule inhibitor of tyrosine kinases that is approved for the treatment of advanced renal cell carcinoma and some cases of hepatocellular carcinoma. One of the kinases that sorafenib inhibits is involved in the signaling pathway that is initiated when VEGF binds to its receptors. As a result, new blood vessel development is halted. Sorafenib also blocks an enzyme that is involved in cell growth and division.
    • Sunitinib (Sutent®) is another small-molecule tyrosine kinase inhibitor that is approved for the treatment of patients with metastatic renal cell carcinoma, gastrointestinal stromal tumor that is not responding to imatinib, or pancreatic neuroendocrine tumors that cannot be removed by surgery, are locally advanced, or have metastasized. Sunitinib blocks kinases involved in VEGF signaling, thereby inhibiting angiogenesis and cell proliferation.
    • Pazopanib (Votrient®) is approved to treat patients with advanced renal cell carcinoma and advanced soft tissue sarcoma. Pazopanib is a small-molecule inhibitor of several tyrosine kinases, including VEGF receptors, c-KIT, and platelet-derived growth factor receptor (PDGFR).
    • Regorafenib (Stivarga®) is approved for the treatment of some patients with metastatic colorectal cancer. Regorafenib is a small-molecule inhibitor of several tyrosine kinases that are involved in angiogenesis and tumor cell growth, including VEGF receptors, the angiopoietin-1 receptor (TIE2), PDGFR, RET, c-KIT, and RAF.
    • Cabozantinib (Cometriq™) is approved for the treatment of some patients with metastatic medullary thyroid cancer. Cabozantinib is a small-molecule inhibitor of several tyrosine kinases, including VEGF receptors, RET, MET, TRKB, and TIE2.

    Some targeted therapies act by helping the immune system to destroy cancer cells.

    • Rituximab (Rituxan®) is a monoclonal antibody that is approved to treat certain types of B-cell non-Hodgkin lymphoma and, when combined with other drugs, to treat chronic lymphocytic leukemia (CLL). The therapy recognizes a molecule called CD20 that is found on B cells. When rituximab binds to these cells, it triggers an immune response that results in their destruction. Rituximab may also induce apoptosis.
    • Alemtuzumab (Campath®) is approved to treat patients with B-cell CLL. The therapy is a monoclonal antibody directed against CD52, a protein found on the surface of normal and malignant B and T cells and many other cells of the immune system. Binding of alemtuzumab to CD52 triggers an immune response that destroys the cells.
    • Ofatumumab (Arzerra®) is approved for the treatment of some patients with CLL that does not respond to treatment with fludarabine and alemtuzumab. This monoclonal antibody is directed against the B-cell CD20 cell surface antigen.
    • Ipilimumab (Yervoy™) is approved to treat patients with unresectable or metastatic melanoma. This monoclonal antibody is directed against cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), which is expressed on the surface of activated T cells as part of a “checkpoint” to prevent a runaway immune response. By inhibiting CTLA-4, ipilimumab stimulates the immune system to attack melanoma cells.

    Another class of targeted therapies includes monoclonal antibodies that deliver toxic molecules to cancer cells specifically.

    • Tositumomab and 131I-tositumomab (Bexxar®) is approved to treat certain types of B-cell non-Hodgkin lymphoma. The therapy is a mixture of monoclonal antibodies that recognize the CD20 molecule. Some of the antibodies in the mixture are linked to a radioactive substance called iodine-131. The 131I-tositumomab component delivers radioactive energy to CD20-expressing B cells specifically, reducing collateral damage to normal cells. In addition, the binding of tositumomab to the CD20-expressing B cells triggers the immune system to destroy these cells.
    • Ibritumomab tiuxetan (Zevalin®) is approved to treat some patients with B-cell non-Hodgkin lymphoma. The therapy is a monoclonal antibody directed against CD20 that is linked to a molecule that can bind radioisotopes such as indium-111 or yttrium-90. The radiolabeled forms of Zevalin deliver a high dose of radioactivity to cells that express CD20.
    • Denileukin diftitox (Ontak®) is approved to treat some patients with CTCL. Denileukin diftitox consists of interleukin-2 (IL-2) protein sequences fused to diphtheria toxin. The drug binds to cell surface IL-2 receptors, which are found on certain immune cells and some cancer cells, directing the cytotoxic action of the diphtheria toxin to these cells.
    • Brentuximab vedotin (Adcetris®) is approved for the treatment of systemic anaplastic large cell lymphoma and Hodgkin lymphoma that has not responded to prior chemotherapy or autologous stem cell transplantation. This agent consists of a monoclonal antibody directed against a molecule called CD30, which is found on some lymphoma cells, linked to a drug called monomethyl auristatin E (MMAE). The antibody part of the agent binds to and is internalized by CD30-expressing tumor cells. Once inside the cell, the MMAE is released, where it induces cell cycle arrest and apoptosis.

    Cancer vaccines and gene therapy are often considered to be targeted therapies because they interfere with the growth of specific cancer cells. Information about these treatments can be found in the following NCI fact sheets, which are available online or by calling NCI’s Cancer Information Service at 1–800–4–CANCER:

    • Biological Therapies for Cancer includes information about monoclonal antibodies and cancer vaccines.
    • Cancer Vaccines contains information on vaccines intended to treat cancer, as well as those intended to prevent it.
    • Gene Therapy for Cancer discusses research with genetic material in developing cancer therapies, including risks, benefits, and ethical issues.
  6. What impact will targeted therapies have on cancer treatment?Targeted cancer therapies give doctors a better way to tailor cancer treatment, especially when a target is present in some but not all tumors of a particular type, as is the case for HER-2. Eventually, treatments may be individualized based on the unique set of molecular targets produced by the patient’s tumor. Targeted cancer therapies also hold the promise of being more selective for cancer cells than normal cells, thus harming fewer normal cells, reducing side effects, and improving quality of life.

    Nevertheless, targeted therapies have some limitations. Chief among these is the potential for cells to develop resistance to them. In some patients who have developed resistance to imatinib, for example, a mutation in the BCR-ABL gene has arisen that changes the shape of the protein so that it no longer binds this drug as well. In most cases, another targeted therapy that could overcome this resistance is not available. It is for this reason that targeted therapies may work best in combination, either with other targeted therapies or with more traditional therapies.

  7. Where can I find information about clinical trials of targeted therapies?The list below provides links to active clinical trials of FDA-approved targeted therapies. Because trials begin and end regularly, it is possible that, at any given time, a particular drug will not have any trials available. If you are viewing this fact sheet online, the drug names are links to search results for trials in NCI’s clinical trials database. For information about how to search the database, see “Help Using the NCI Clinical Trials Search Form.” The database includes all NCI-funded clinical trials and many other studies conducted by investigators at hospitals and medical centers in the United States and other countries around the world.

    Targeted Cancer Therapies Being Studied in Clinical Trials:
    Alemtuzumab (Campath®)

    Alitretinoin (Panretin®)
    Anastrozole (Arimidex®)
    Bevacizumab (Avastin®)
    Bexarotene (Targretin®)
    Bortezomib (Velcade®)
    Bosutinib (Bosulif®)
    Brentuximab vedotin (Adcetris®)
    Cabozantinib (Cometriq™)
    Carfilzomib (Kyprolis™)
    Cetuximab (Erbitux®)
    Crizotinib (Xalkori®)
    Dasatinib (Sprycel®)
    Denileukin diftitox (Ontak®)
    Erlotinib hydrochloride (Tarceva®)
    Everolimus (Afinitor®)
    Exemestane (Aromasin®)
    Fulvestrant (Faslodex®)
    Gefitinib (Iressa®)
    Ibritumomab tiuxetan (Zevalin®)
    Imatinib mesylate (Gleevec®)
    Ipilimumab (Yervoy™)
    Lapatinib ditosylate (Tykerb®)
    Letrozole (Femara®)
    Nilotinib (Tasigna®)
    Ofatumumab (Arzerra®)
    Panitumumab (Vectibix®)
    Pazopanib hydrochloride (Votrient®)
    Pertuzumab (Perjeta™)
    Pralatrexate (Folotyn®)
    Regorafenib (Stivarga®)
    Rituximab (Rituxan®)
    Romidepsin (Istodax®)
    Sorafenib tosylate (Nexavar®)
    Sunitinib malate (Sutent®)
    Temsirolimus (Torisel®)
    Toremifene (Fareston®)
    Tositumomab and 131I-tositumomab (Bexxar®)
    Trastuzumab (Herceptin®)
    Tretinoin (Vesanoid®)
    Vandetanib (Caprelsa®)
    Vemurafenib (Zelboraf®)
    Vorinostat (Zolinza®)
    Ziv-aflibercept (Zaltrap®)

  8. What are some resources for more information?NCI’s Molecular Targets Laboratory (MTL), part of NCI’s Center for Cancer Research (CCR), is working to identify and evaluate molecular targets that may be candidates for drug development. The initial goal of the MTL is to facilitate the discovery of compounds that may serve as bioprobes for functional genomics, proteomics, and molecular target validation research, as well as leads or candidates for drug development.

    NCI’s Chemical Biology Consortium (CBC) facilitates the discovery and development of new agents to treat cancer. The CBC is part of the NCI Experimental Therapeutics Program, which is a collaborative effort of CCR and NCI’s Division of Cancer Treatment and Diagnosis.

High Healthcare Cost – What went wrong with our health system?

By Dr Tan Cheng Bock

Some background is important to understand our healthcare system. The big change in health care came when the government decided in the late 1980’s to make health an INDUSTRY ie medical industry to add value to our GDP. To do that Singapore must be a centre of medical excellence. So the ministry sold the idea of medical excellence to the extreme and embarked on huge hospital buildings with unnecessary frills and high administration costs. Government also restructured many hospitals into hotel like complexes.

But were these hospitals built for the people? I think it was more for the medical industry. Thus these were grand, impersonal general hospitals with equally big specialist wings. Not only the public sector but the private hospitals were encouraged to expand. Let the private hospitals chase the medical tourism dollar but our public hospitals must take care of our citizens first.. To justify the cost of such big hospitals with expensive special medical equipment, demand was created through their PR unit and the press.

Singaporeans were so taken up by this change that everyone wants to go to hospital even for minor ailments like minor cuts, coughs and colds. As Medisave was allowed to be used for hospitalisation only, many procedures which could be done outside hospital, were done in hospital at much higher cost. I remembered then, many Singaporeans opted for A class when they could use their medisave. Very quickly their medisave(their own money) were depleted. Also as nursing homes stay could not use Medisave many plead with hospital authorities to allow their sick relatives to stay longer. So hospitals face overcrowding. Over time Singaporeans tend to regard hospitals as a better choice to go for treatment than elsewhere .

Thus MOH have impressed upon Singaporeans the wrong thinking that the management of their health problems is at the hospital or specialist level. This mindset behaviour to opt for hospital/specialist treatment must be reversed or cost will continue to rise and people’s CPF & Medisave drained.

This mindset change can only happen if Singaporeans find value in the way we look after their health needs at the community cost level, effectively and efficiently. This is a challenge for MOH as primary health care is a less visible program than hospitals. It takes time, commitment, adequate funding, hard work and a strong political will to change. MOH must do something to bring about this change.

We must shift expensive hospital care to less expensive non hospital care through an efficient primary care program or Singaporeans will have no peace of mind.

The way to bring down health cost is to cut down hospital/specialist visits through an island wide Preventive Care Program. How much we pay for our health bills depend on the system we have. I believe the current system is expensive, depend too much on CPF to fund and we should review.


The government Hospitals versus the Private. What is the use of the government hospitals competing with the private but monopolised the entire market and causing the ever rising healthcare costs? Now even my medisave cannot even cover my yearly payments and I need to fork out about additional $100 every visit for outpatient for my diabetes treatments. Primary healthcare should be taken care by the private sector so that competition will drive the costs down, with only polyclinics administered by the governments to compete, even separating the business of dispensing medication. Why should we let the government drive us to the wall? Who will you chose when the healthcare costs of both public and private is about the same, but in public you get training doctors who use you as guinea pigs, or private with experienced doctors, but the government has skewed the entire medical healthcare markets, the best doctors now have to be turned surgeons in large hospitals in order to make good money, but can private clinics doctors do the same? Definitely YES, when they specialised. SUBSIDISED Healthcare? I can now afford to see private clinic doctors, who wants to be guinea pigs.

– Contributed by Oogle.