Positive phase II clinical results of abiraterone (for advanced prostate cancer)....

We know that,  Abiraterone (discovered and developed at the Institute of Cancer Research in London, see structure) is a drug under investigation for use in hormone-refractory prostate cancer (prostate cancer not responding to treatment with antiandrogens). Abiraterone acts  by blocking the formation of testosterone by inhibiting CYP17A1 (CYP450c17), an enzyme also known as 17α-hydroxylase/17,20 lyase.  This enzyme is involved in the formation of DHEA and androstenedione, which may ultimately be metabolized into testosterone.

 

The latest trial, which was led by the ICR and the Royal Marsden  NHS Foundation Trust, is the first to investigate the drug in men with such advanced prostate cancer.

A total of 47 men were recruited for the trial, all of whom had late-stage castration-resistant prostate cancer, which means that their disease was advanced and their tumors were no longer responsive to androgen deprivation therapy. In almost all cases, the men's cancer had spread to their bones. All of the participants had already received hormone therapy and the chemotherapy drug docetaxel, but were no longer responding to those treatments. By the end of the study period, researchers found that around three-quarters of men had experienced a drop in levels of prostate specific antigen (PSA), which is often raised in men with prostate cancer and can be used to measure disease activity.

 In around half of the men,  PSA levels fell by at least 50 per cent, while three-quarters of participants also had a drop in the number of tumor cells circulating in their blood. Three years after the start of the trial, five of the patients were still taking abiraterone and benefitting from the treatment. Lead researcher Dr Alison Reid, also from the ICR and the Royal Marsden, noted that "abiraterone shrank or stabilised men's cancers for an average of almost six months, which is a very impressive result with only mild side-effects". 

Though the initial results are exciting, the researchers conclude that there's a lot more work needed to establish what abiraterone's place will be in treating men with prostate cancer....

Ref :http://info.cancerresearchuk.org/news/archive/cancernews/2010-02-16-New-drug-shows-promise-for-advanced-prostate-cancer-patients

Triapine with cisplatin a new standard of care for cervical cancer?

In continuation of my update on cancer drug development,   I found this  info interesting to share with. Researchers  lead by Dr. Charles Kunos at the Ireland Cancer Center of University Hospitals (UH)  have found that,  Triapine, (3-aminopyridine-2-carbox -aldehyde   thiosemicarbazone, see structure), which suppresses tumor growth shows a great deal of promise for cervical cancer patients who are at high risk for relapse and cancer-related death. 

The phase I study found that the chemotherapy medicine  Triapine, was well tolerated in combination with standard-of-care cisplatin chemotherapy and radiation treatment in women with cervical cancer. This regimen provided both significant reduction in cancer disease and cancer control.

In the study   (ten-patient study) patients,  were treated three times weekly with Triapine (a potent Ribonucleotide Reductase Inhibitor) in combination with weekly cisplatin treatment and daily pelvic radiation therapy over five weeks.  The researchers claims that  "a 100% complete response rate was observed and no disease progression was documented through 18 months of median follow-up."A phase two follow-up study is ongoing at the Ireland Cancer Center. UH Case Medical Center  Hope this new found combintaton will be  a promising new treatment to help women fight this aggressive disease in the days to come...

Ref : http://clincancerres.aacrjournals.org/content/16/4/1298.abstract?sid=f3df7c2d-9e46-4baf-b47b-83d310b87641

Enantioselective synthesis of Kinamycin F - a new hope for anticancer drug development ?

The kinamycins are a series of naturally occurring compounds endowed with intriguing molecular architectures and potent biological properties such as  antibiotic and antitumor activities. These novel diazofluorene-containing compounds defied chemical synthesis since their initial disclosure by Omura et al. in 1970 until the first total synthesis of kinamycin C by Porco et al. in late 2006.

Now, researchers from Yale University,  have  developed a new method to recreate this structure that allows them to synthesize the kinamycins with much greater efficiency than previously possible.

As per the claim by the researchers,  key to the success of the route was  the development of a three-step sequence for construction of the diazonapthoquinone (diazofluorene, blue in structure source : JACS) function of the natural product.

While scientists have produced kinamycins in the laboratory in the past, the Yale team was able to halve the number of steps required to go from simple, easily obtainable precursors to the complete molecule from 24 down to 12. 

This sequence comprises fluoride-mediated coupling of a β-(trimethylsilylmethyl)-cyclohexenone and halonapthoquinone, palladium-mediated cyclization to construct the tetracyclic scaffold of the natural product, and mild diazo-transfer to a complex cyclopentadiene to introduce the diazo function. Ortho-quinone methide intermediates, formed by reduction and loss of dinitrogen from (structure), have been postulated to form in vivo, and this approach provides a straightforward synthetic pathway to such compounds.

This research is of great importance because by shortening the synthesis one can now prepare these molecules in the quantities required for further studies, including animal studies and even clinical trials.

Working with researchers at the Yale School of Medicine and the Yale Chemical Genomics Screening Facility, the team has begun testing several of the compounds against cancer cells, with promising preliminary results. Next, they will work to understand the exact mechanism that makes the compounds,  which are benign on their own  highly toxic once they penetrate cells. Lead researcher Dr. Seth Herzon, says "the key to success will be whether they can develop selectivity - whether they can kill cancer cells in the presence of non-cancerous tissue". Dr.Herzon  is also optimistic about lomaiviticin A (which also has the reactive core kinamycin,  and is even more toxic and could prove even more effective in destroying cancer cells)...let us hope positive results from this study....

Ref : http://pubs.acs.org/doi/abs/10.1021/ja910769j 

Celastrol Inhibiting Hsp90 Chaperoning - a new way to treat cancer?

Celastrol, derived from trees and shrubs called celastracaea,  (Thunder of God Vine) has been used for centuries in China to treat symptoms such as fever, chills, joint pain and inflammation.Celastrol has been shown to possess antioxidant, anti-inflammatory activities. The same compound has been tried for Alzheimer's disease and anticancer activity  also.

Now Dr. Ahmed Chadli, has come up with an interesting findings i.e., Celastrol may play a role in cancer treatment by inactivating a protein required for cancer growth.  Protein, P23, is one of many proteins helping the heat shock protein 90. Dr. Chadli claims that,  "scientists are just beginning to realize the potential of controlling inflammation-related diseases, including cancer, by inhibiting HSP90".

As per  claim by Dr. Chadli, cancer cells need HSP90 more than normal cells because cancer cells have thousands of mutations. They need chaperones all the time to keep their mutated proteins active. By taking heat shock proteins away from cells, the stabilization is taken away and cell death occurs. 

Most HSP90 inhibitors lack selectivity, disabling the functions of all proteins activated by HSP90 rather than only the ones implicated in a specific tumor and proteins vary from one tumor to another. Dr. Chadli and colleagues at the Mayo Clinic believe celastrol holds the key to specificity, targeting the HSP90-activated protein required for folding steroid receptors.

Celastrol inhibits the Hsp90 chaperoning machinery by inactivating the co-chaperone p23, resulting in a more selective destabilization of steroid receptors compared with kinase clients. Both in vitro and in vivo results demonstrate that celastrol disrupts p23 function by altering its three-dimensional structure, leading to rapid formation of amyloid-like fibrils. This study reveals a unique inhibition mechanism of p23 by a small molecule that could be exploited in the dissection of protein fibrillization processes as well as in the therapeutics of steroid receptor-dependent diseases....

Ref : http://www.jbc.org/content/285/6/4224.abstract

FDAs approval of Lapatinib in combination with Letrozole to treat breast cancer...

In my earlier blog, I mentioned about the combination of Lapatinib and Trastuzumab for breast cancer treatment. Now FDA has  approved Lapatinib in combination with Letrozole (see structure ; Letrozole trade name Femara, an oral non-steroidal aromatase inhibitor for the treatment of hormonally-responsive breast cancer after surgery)  to treat hormone positive and HER2-positive advanced breast cancer in postmenopausal women for whom hormonal therapy is indicated. This drug combination of  Lapatinib  & Letrozole provides women being treated for advanced breast cancer with an important treatment option. 

The entirely oral treatment regimen works by targeting both HER2 and the hormone receptors, thereby slowing the cancer cells' ability to grow or spread. As per the claim by  Dr. Richard Pazdur, (Director, Office of Oncology Drug Products, FDA's Center for Drug Evaluation and Research) women with HER2-positive disease receiving the Lapatinib plus Letrozole combination more than doubled the time they lived without the cancer progressing compared with those receiving Letrozole alone (35 weeks vs. 13 weeks).

Lapatinib, was initially approved in combination with a chemotherapy drug, Xeloda (capecitabine) in 2007. This combination was used to treat women with advanced breast cancer tumors with the HER2 protein who had received prior treatment with chemotherapy drugs, including an anthracycline and a taxane, and Herceptin (trastuzumab), an anti-cancer antibody used to treat HER2-positive advanced breast cancer. Safety information from this study was consistent with previous Lapatinib clinical studies in advanced breast cancer. The most commonly reported side effects of the combination were diarrhea, rash, nausea and fatigue. Still clinical trials are to be carried out, in my opinion its a good achievement...

Ref : http://www.prnewswire.com/news-releases/fda-expands-use-of-approved-breast-cancer-drug-83072502.html

Positive results from Phase 2 trial of picoplatin for colorectal cancer...

In continuation of my update on picoplatin,.......

Poniard Pharmaceuticals, Inc,  claims that Phase 2 trial  study met its primary objective, that is picoplatin in combination with 5-fluorouracil and leucovorin (FOLPI regimen) was associated with a statistically significant reduction in neurotoxicity (p <0.004) compared to oxaliplatin given in combination with 5-fluorouracil and leucovorin (FOLFOX regimen). More...

DBZ an Alzheimer drug in clinical trails - a new hope for oesophageal cancer ?

Though there are some drugs for other cancers, but there is no good treatment, and sufferers for the cancer of  oesophagus  or gullet  and the patients  frequently face a short, painful battle which ends all too quickly in death. Many of the cancers diagnosed are in people with a long history of heartburn.

About Oesophagus cancer :

Chronic heartburn leads to the lower parts of the gullet being bathed in a toxic acid solution, and the lining of the gullet defends itself against this by changing itself into something which looks a lot like the lining of the lower intestines. Although the damaged tissue, called Barrett's oesophagus, is not cancerous in itself, its presence warns doctors that the patient has taken the first step towards cancer, and triggers a rigorous programme of monitoring, coupled with therapy to prevent further damage.

Patients with Barrett's oesophagus can be stabilised, and most do not go on to develop cancer, but once it is there, the mutated tissue is almost impossible to eradicate, so the risk always remains. Researchers have long been searching for new drugs able to revert Barrett's oesophagus to the healthy, normal lining of the gullet, and now, a team led by Hans Clevers of the Hubrecht Institute, Utrecht, have come up with a drug DBZ (see structure : source : Paul J. Ciaccio)  a drug already in clinical trails for the Alzheimer's disease.

The interesting part of this research is the basis for testing the drug. Clevers' team, whose research into colon cancer is world-renowned, reasoned that as Barrett's oesophagus cells are very similar to the cells which line the colon, they might share vital control pathways.

Clevers and his team then put this together with the fact that  the anti-Alzheimer's drug DBZ, currently in clinical trials, is known to have side effects on the lower gut lining. Researchers used a rat model of oesophageal cancer to observe the effects of DBZ on Barrett's oesophagus tissue, and found that DBZ could halt the growth of Barrett's oesophagus, and in some cases completely destroyed the mutant tissue. Whilst the treatment is still a long way from being trialled in humans, it is an exciting step forward in the fight for a cure for oesophageal cancer.

New hope for therapy in heartburn-related cancer is presented in the Research Article entitled 'Conversion of metaplastic Barrett's epithelium into post-mitotic goblet cells by gamma-secretase inhibition',

Hans Clevers et. al., Disease Models & Mechanisms (DMM), Vol3, Issue 1/2,

I found an interesting article in the similar lines, those interested can read at the link...

Pomegranates May Prevent Growth of Breast cancer cells.....

We know that Pomegranate aril juice provides about 16% of an adult's daily vitamin C requirement per 100 ml serving, and is a good source of vitamin B₅ (pantothenic acid), potassium and antioxidant polyphenols.  The most abundant polyphenols in pomegranate juice are the hydrolyzable tannins called punicalagins which have free-radical scavenging properties in laboratory experiments. Punicalagins are absorbed into the human body and may have dietary value as antioxidants. Other phytochemicals include polyphenols catechins, gallocatechins, and anthocyanins such as prodelphinidins, delphinidin, cyanidin, and pelargonidin.   Many food and dietary supplement makers have found advantages of using pomegranate phenolic extracts as ingredients in their products instead of the juice. One of these extracts is ellagic acid which may become bioavailable only after parent molecule punicalagins are metabolized. However, ingested ellagic acid from pomegranate juice does not accumulate in the blood in significant quantities and is rapidly excreted. Accordingly, ellagic acid from pomegranate juice does not appear to be biologically important in vivo.

Now researchers lead by Dr Shiuan Chen, director of the Division of Tumour Cell Biology, and Dr Lynn Adams, a research fellow at the centre's Beckman Research Institute have found that Pomegranates contain a group of compounds called ellagitannins ( glucosidesof elligacic acid) may prevent the growth of breast cancer cells. Researchers tried to determine whether chemicals in pomegranates could block the action of an enzyme called aromatase. Aromatase plays a key role in driving the growth of some forms of breast cancer by helping the body produce the female sex hormone oestrogen. Breast cancer drugs like anastrozole are designed to block its action.

The researchers screened ten ellagitannin-like compounds and found that one in particular, Urolithin B, (see above structure) significantly inhibited breast cancer cell growth in the laboratory. Its interesting to note that phytochemicals in pomegranates to exhibit this property (earlier the same authors have reported the inhibition of aromatase by grapes (phytochemicals).

Though further studies like in vivo are essential to further substantiate the in vitro studies (relatively high levels of ellagitannin compounds were required to demonstrate an anti-proliferative effect on cultured breast cancer cells) are essential (because of the fact that  the ellagitannins are not well absorbed into blood when provided in the diet), still in my opinion its a good finding......

^{Ref : http://cancerpreventionresearch.aacrjournals.org/cgi/content/abstract/3/1/108}

Celecoxib reduces the risk of common skin cancer in humans.....

We know that Celecoxib   is a non-steroidal anti-inflammatory drug (NSAID)  used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms, and to reduce numbers of colon and rectum polyps in patients with familial adenomatous polyposis. It is marketed by Pfizer. It is known under the brand name Celebrex or Celebra for arthritis and Onsenal for polyps. Celecoxib is available by prescription in capsule form.

Researchers from UC-San Francisco and Children's Hospital Oakland,  (Dr. Tang was was an assistant professor at UC-San Francisco and Children’s Hospital Oakland  when the trial was conducted) have come up with very interesting results for the same drug. The drug can reduce the risk of a common skin cancer in humans. Though celecoxib, is associated with an increased risk of heart attack and stroke in some people, it's possible that topical application could have a safer, protective effect for people prone to developing the cancers, called basal cell carcinomas, the researcher believes.

For the current research, Tang and her colleagues capitalized on a previous finding suggesting that celecoxib, a NSAID, can inhibit the development of a different kind of skin cancer, squamous cell carcinoma, in mice. They wondered if the drug, sold by the pharmaceutical company Pfizer under the brand names Celebrex and Onsenal, would have a similar effect on the more common basal cell carcinoma.

Celecoxib is thought to work to prevent or slow cancer growth by interfering with the action of an enzyme called Cox-2, which causes tissue inflammation (pro inflammator). Celecoxib has both pain-killing (analgesic) and anti-inflammatory properties. Chronic inflammation has long been associated with the development of many types of cancer, and celecoxib has been shown in clinical trials to reduce the incidence of colon cancer in people with a genetic predisposition to the disease.

Interestingly, researchers stopped the clinical trials in 2003 (from 2001) when the study lead to high risk  of heart attack and stroke in patients taking a different NSAID. (Rofecoxib,  Vioxx by  Merck & Co. was withdrawn from the market by Merck in 2004  and Tang's trial was discontinued that year in response to ongoing concerns about long-term treatment with Cox-2 inhibitors). At that time, most participants had received about two years of drug treatment. No patient died or suffered adverse cardiovascular events due to their participation in the trial. Although drug treatment had been discontinued, the researchers continued to monitor basal cell carcinoma formation in people who had received the drug or placebo for an additional year to complete the three-year study. They found that, although both groups continued to develop new cancers during the study, oral celecoxib treatment decreased the growth of skin tumors by about 50 percent as compared to placebo in participants who entered the trial with 15 or fewer basal cell carcinomas. Celecoxib treatment also reduced the overall tumor burden in the  group of patients (where in the carcinomas are removed upon diagnosis in most people).

Now the lead researcher Dr. Tang is continuing her focus on skin cancer prevention at Stanford. She's currently investigating whether it's possible to develop a topical formulation of the drug that can be applied directly to the skin to achieve a similar protective effect without associated cardiovascular risk. Hope she will get positive results via topical formulation .....

In my opinion  its really a great achievement.We know that compounds with selective inhibitors of 5-LO (Lipoxygenase) and COX (Cyclooxegenase, that too COX-II) will be  the best NSAIDs without any ulcerogenecity, its good see that the  same compounds can be used to treat skin cancer....

Ref : http://med.stanford.edu/ism/2010/january/tang.html

Imetelstat (GRN 163L) shows promising results against brain cancer glioblastoma and prostate cancer...

In continuation of my update on Telomerase inhibitors, I find this info really interesting and hence sharing here with. As mentioned in my earlier blog about imetelstat (GRN163L )  has been undergoing Phase I clinical trials designed to examine the safety, tolerability, pharmacokinetics and pharmacodynamics of the drug, alone or in combination, in solid tumors, chronic lymphoproliferative disease, multiple myeloma, lung and breast cancers and the company claims that Phase I objectives for imetelstat  (structure) have been achieved. Now  Dr. Jerry Shay, professor of cell biology of  The University of Texas Southwestern Medical Center at Dallas, claims that the same drug shows promise in fighting the brain cancer glioblastoma and prostate cancer.

Glioblastomas are the most common malignant brain tumors in adults, according to the American Cancer Society. They are difficult to treat with drugs because blood vessels in the brain have tightly constructed walls that allow only a few substances to pass through.

The researcher focused on cells called tumor-initiating cells. Some researchers believe that tumors contain a small subset of initiating cells – or cancer stem cells – that are able to initiate and drive tumors and that are often resistant to radiation therapy and chemotherapy.

In the glioblastoma study, Dr. Shay and his colleagues found that imetelstat blocked the action of telomerase in isolated tumor-initiating cells as well as the bulk of the tumor cells, eventually killing the cells. Combining imetelstat with radiation and a standard chemotherapy drug made imetelstat even more effective. When the researchers implanted human tumor-initiating cells into rodents, they found that imetelstat was able to enter brain tissue and inhibit telomerase activity.

In the prostate cancer study, the researchers isolated tumor-initiating cells from human prostate cancer cells. The cells showed significant telomerase activity. Imetelstat blocked the enzyme’s activity, and telomeres shortened greatly. As per Dr.Shay, since the drug attacks a mechanism that is active in most cancers, it might prove to be widely useful, especially when combined with other therapies.

Hope  Geron people must be really happy for these results  and conclusions.....

Ref : http://www.utsouthwestern.edu/utsw/cda/dept353744/files/570509.html

Mitaplatin as a better anticancer agent.......

In continuation of my update on Platinum compounds as anticancer drugs, I find  this one more interesting info to share with. MIT chemists have developed a new platinum compound that is as powerful as the commonly used anticancer drug cisplatin but better able to destroy tumor cells.

As per the claim by the researchers, glycolytic metabolism of most solid tumors, known as the Warburg effect, is associated with resistance to apoptosis that enables cancer cells to survive. Dichloroacetate (DCA) is an anticancer agent that can reverse the Warburg effect by inhibiting a key enzyme in cancer cells, pyruvate dehydrogenase kinase (PDK), that is required for the process. DCA is currently not approved for cancer treatment in the USA. With this idea behind researchers have prepared the new compound by combining dichloroacetate, DCA and cisplatin. Mitaplatin, thus obtained has two DCA units which are appended to the axial positions of a six-coordinate Pt (IV) center.

As per the claim by the authors, the negative intracellular redox potential reduces the platinum to release cisplatin, a Pt (II) compound, and two equivalents of DCA. By a unique mechanism, mitaplatin thereby attacks both nuclear DNA with cisplatin and mitochondria with DCA selectively in cancer cells. The cytotoxicity of mitaplatin in a variety of cancer cell lines equals or exceeds that of all known Pt (IV) compounds and is comparable to that of cisplatin.

Mitaplatin alters the mitochondrial membrane potential gradient of cancer cells, promoting apoptosis by releasing cytochrome c and translocating apoptosis inducing factor from mitochondria to the nucleus. Cisplatin formed upon cellular reduction of mitaplatin enters the nucleus and targets DNA to form 1,2-intrastrand d(GpG) cross-links characteristic of its own potency as an anticancer drug. These properties of mitaplatin are manifest in its ability to selectively kill cancer cells cocultured with normal fibroblasts and to partially overcome cisplatin resistance. Further studies like mice transplanted with human tissues are to be substantiated, in my opinion its a good achievement...

Ref : http://www.pnas.org/content/early/2009/12/09/0912276106.abstract?related-urls=yes&legid=pnas;0912276106v1

Mode of action of Cordycepin (a drug from cordyceps mushroom) established.....

We know that Cordycepin, or 3'-deoxyadenosine (known polyadenylation inhibitor),   was initially extracted from fungi of genus Cordyceps, (Cordyceps is a strange parasitic mushroom that grows on caterpillars). 3'-Deoxy adnosine has shown to possess diverse activities such as anti-proliferative, pro-apoptotic and anti-inflammatory effects. Properties attributed to cordyceps mushroom in Chinese medicine made it interesting to investigate and it has been studied for some time. In fact, the first scientific publication on cordycepin was in 1950 . Now it can be prepared from a cultivated form and also by synthetically. The problem was that although cordycepin was a promising drug, it was quickly degraded in the body. Now researcher Dr. de Moor has come up with interesting explanation about how the drug works.

The team has observed two effects on the cells: at a low dose cordycepin inhibits the uncontrolled growth and division of the cells and at high doses it stops cells from sticking together, which also inhibits growth. Both of these effects probably have the same underlying mechanism, which is that cordycepin interferes with how cells make proteins. At low doses cordycepin interferes with the production of mRNA, the molecule that gives instructions on how to assemble a protein. And at higher doses it has a direct impact on the making of proteins. More interestingly, the team has developed a very effective method that can be used to test new, more efficient or more stable versions of the drug in the Petri dish...

Ref : http://www.bbsrc.ac.uk/media/releases/2009/091223-new-insights-mushroom-derived-drug-for-cancer.html

Trabectedin for advanced soft tissue sarcoma....

Patients with a rare form of cancer called advanced soft tissue sarcoma could now benefit from a new drug called trabectedin, after the National Institute for Health and Clinical Excellence (NICE) approved the drug for NHS use.The same drug was given orphan status for ovarian cancer & soft tissue sarcoma by USFDA. Hope patients suffering from soft tissue sarcoma will breathe a sigh of relief.

Research suggests that the drug may extend life by at least three months more than other NHS treatments and that it may therefore be beneficial for some of the 500 to 600 people in England and Wales with advanced soft tissue sarcoma.

Under the latest guidance, the drug is recommended as a treatment for people with advanced soft tissue sarcoma who have previously failed to respond to treatment with anthracyclines and ifosfamide, or who are unable to tolerate those treatments. More...

Pyramidine core- a new drug for drug resistant non small cell lung cancers

Dana-Farber investigators hypothesized current agents lose their potency because they don't bind as tightly or fully to the EGFR T790M protein as they ideally should. To improve the fit, researchers led by chemical biologist Nathanael Gray, PhD, prepared a group of inhibitors with a different structural scaffold, known as a pyrimidine core, which, it was thought, would mesh more thoroughly. They lab-tested the agents in NSCLC cells with EGFR T90M and found several that were up to 100 times more potent than quinazolines [erlotinib (Tarceva), gefitinib (Iressa), and cetuximab (Erbitux)] in restricting cell growth. As an unexpected bonus, these compounds were nearly 100 times less powerful at slowing the growth of cells with normal EGFR, suggesting they would be less likely to produce side effects than current drugs. The agent which performed the best is the pyrimidine WZ4002. Those interested, can watch the video description (Pasi Jänne).

http://www.dana-farber.org/abo/news/press/2009/research-yields-new-agent-for-some-drug-resistant-non-small-cell-lung-cancers.html

Nilotinib more efficiant over Imatinib for (Ph+ CML)....

Nilotinib (see structure) :

Nilotinib, in the form of the hydrochloride monohydrate salt, is a tyrosine kinase inhibitor, approved as Tasigna in USA and the EU for drug - resistant chronic myelogenous leukemia (June 2006), resistant to treatment with imatinib (Gleevec), another tyrosine kinase inhibitor currently used as a first-line treatment.

In a recently held large clinical trial, nilotinib demonstrated greater efficacy over the current gold standard treatment, imatinib, in adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia (Ph+ CML) in the chronic phase.

As per the claim by the researchers, in the first head-to-head study of these two oral treatments as initial therapy for this life-threatening leukaemia, nilotinib demonstrated statistically significant improvement over imatinib in key measures of effectiveness used in the trial. The trial showed that at 12 months, significantly fewer patients on nilotinib 300mg twice-daily progressed from the initial chronic phase of the disease to the later accelerated or blast crisis phases than those on imatinib 400mg once-daily. This demonstrates that nilotinib provided significantly better control of the disease compared to imatinib.

95% of patients with CML have an abnormality known as the Philadelphia chromosome. This chromosome produces a type of protein called Bcr-Abl, which is responsible for the overproduction of the cancerous white blood cells that are the main feature in Ph+ CML. Nilotinib is a potent and selective inhibitor of the Bcr-Abl protein, thereby inhibiting the production of these cancerous cells.

Ref : http://www.novartis.com/newsroom/media-releases/en/2009/1359764.shtml

Combination of Lapatinib and Trastuzumab a better treatment for breast cancer....

Lapatinib or lapatinib ditosylate is an orally active chemotherapeutic drug treatment for solid tumours such as breast cancer. Patients who meet specific indication criteria may be prescribed lapatinib as part of combination therapy for breast cancer. On March 13, 2007, FDA approved lapatinib in combination therapy for breast cancer patients already using capecitabine.

Recently, researchers from Duke University Medical Center. Dr. Kimberly Blackwell have found more interesting results when they did try the combination of Trastuzumab (monoclonal antibody). As per the claim by the researchers, Lapatinib plus trastuzumab are significantly better than lapatinib alone in extending the lives of breast cancer patients whose tumors are HER2-positive.

Blackwell says, the combination targeted therapy gave patients more than a four-month survival advantage over those who took lapatinib alone. She says the findings may be the first step toward a chemotherapy-free future. This is the first time that a pair of targeted therapies has been shown to be superior to any intervention that paired a targeted therapy with a hormonal or chemotherapy based approach, she said. The interesting claim by the researchers trastuzumab binds to and blocks part of the HER2 growth factor that appears on the surface of some breast cancer cells while lapatinib binds to a second growth factor, EGFR, and part of HER2 that sits below the cell surface. It's sort of a double whammy, disabling the HER2 protein in two places instead of one......

Ref : http://www.dukehealth.org/health_library/news/targeted_therapy_prolongs_life_in_patients_with_her2_positive_breast_cancer

Bisphosphonates play a role in reducing recurrent breast cancer....

We know that bisphosphonates (also called diphosphonates) are a class of drugs that prevent the loss of bone mass, used to treat osteoporosis and similar diseases. Bone has constant turnover, and is kept in balance (homeostasis) by osteoblasts creating bone and osteoclasts digesting bone. Bisphosphonates inhibit the digestion of bone by osteoclasts. Osteoclasts also have constant turnover and normally destroy themselves by a process called cell suicide (apoptosis). Bisphosphonates encourage osteoclasts to undergo apoptosis. Though other uses like in he treatments of osteoporosis, osteitis deformans, bone metastasis, primary multiple myeloma,hyperparathyroidism and osteogenesis imperfecta were known. A new data suggests that these agents may play a role in reducing recurrent breast cancer as well. Zoledronic acid (see the structure) is both safe and effective in preventing bone loss in postmenopausal women with breast cancer who are treated with aromatase inhibitors, according to data presented at the CTRC-AACR San Antonio Breast Cancer Symposium. Women who take aromatase inhibitors need some sort of bone protection, and this five-year data show that zoledronic acid is a viable option.

As per the claim by the researchers lead by Dr. Adam Brufsky , women who are on Medicare tend to go with tamoxifen because the cost of anastrozole puts them squarely in the donut hole of Medicare Part D, but once the cost barrier is removed there will likely be a mass switch to the aromatase inhibitor, which will necessitate the need for bone protection. More interestingly, in the same conference a research group lead by Rowan Chlebowski presented a study wherein "women who used bisphosphonates, had significantly fewer invasive breast cancers than women who did not use bisphosphonates. .......

http://www.upci.upmc.edu/news/upci_news/121009_study.cfm

Xanthohumol may help in preventing prostate cancer....

We know that Xanthohumol is a Xanthone (phenylated chalcone or Phenylflavonoid). Xanthohumol was initially detected in an extract(series of Humulones) from Hops (Humulus lupulus) and is present in beer. This prenylated flavonoid has been shown to be a potent bioactive compound. Xanthohumol has been shown to have antiproliferative and cytotoxic effects in human cancer cell lines. It has also been displayed to inhibit diacyl glycerol acetyl transferase (DGAT) and human P450 enzymes. Xanthohumol inhibits the expression of HIF-1a and VEGF under hyposic conditions.

Higher antioxidant activity is reported for prenylchalcones than for prenyl flavanones in the Cu2+- mediated oxidation of LDL, suggesting a relation between structure and function. Also, many chalcones suppress tumor promotion more effectively than flavonoids themselves.

Quantities of xanthohumol found in Hop are to small to have any biological effects under normal consumption amounts. Some of the researchers also claims that it has got anti-HIV-1 activity too.

Now researchers from German Cancer Research Center, in Heidelberg, Germany, have come up with more interesting result, i.e., Xanthohumol may aid in preventing prostate cancer. As per the claim by the authors, the compound blocks the effects of the male hormone testosterone.

Studies to date have shown that xanthohumol blocks the action of estrogen by binding to its receptor, which may lead to prevention of breast cancer. Since testosterone receptors act similarly to that of estrogen — by binding, then stimulating hormone-dependent effects, such as gene expression and cell growth — the researchers examined whether xanthohumol might not only block the effects of estrogen, but also of the male hormone androgen. Xanthohumol prevented the receptor from translocating to the cell nucleus, thus inhibiting its potential to stimulate the secretion of PSA and other hormone-dependent effects.

The interesting part of their research is the molecular modeling results, which showed that xanthohumol directly binds to the androgen receptor structure. The researchers suggest that this compound may have beneficial effects in animals — when they measured the anti-androgenic potential of xanthohumol in a rat model, they found that although xanthohumol was not able to prevent an increase in prostate weight after testosterone treatment, it could reduce testosterone-increased seminal vesicle weight.

As per the claim by the researchers the prostate weights were not changed, xanthohumol still reduced the effects of hormone signaling, such as gene expression, measured in the prostate tissue...

Ref : http://mct.aacrjournals.org/content/1/11/959.full

Anticancer & Antiinflammatory properties of Lunasin (Soy Peptide) established ?...

We know that many researchers have tried to establish the anticancer activity of the peptide lunasin (which has been already accepted as neutraceutical agent). Now researchers from University of Illinois have come up with more interesting facts, Soy peptide often discarded in the waste streams of soy-processing plants, may have important health benefits that include fighting leukemia and blocking the inflammation that accompanies such chronic health conditions as diabetes, heart disease, and stroke.

The researchers confirmed lunasin's bioavailability in the human body by doing a third study in which men consumed 50 grams of soy protein--one soy milk shake and a serving of soy chili daily-for five days. Significant levels of the peptide in the participants' blood give us confidence that lunasin-rich soy foods can be important in providing these health benefits.

In the cancer study, de Mejia's group identified a key sequence of amino acids- arginine, glycine, and aspartic acid, (the RGD motif)--that triggered the death of leukemia cells by activating a protein called caspase-3. The scientists also verified lunasin's ability to inhibit topoisomerase 2, an enzyme that marks the development of cancer, and they were able to quantify the number of leukemia cells that were killed after treatment with lunasin in laboratory experiments.

More interesting out come of their study is lunasin's potential anti-inflammatory activity, (first time) they showed that lunasin blocked or reduced the activation of an important marker called NF-kappa-B, a link in the chain of biochemical events that cause inflammation. They also found statistically significant reductions in interleukin-1 and interleukin-6, both important players in the inflammatory process (the reduction in interleukin-6 was particularly strong). As per the claim by the group, although the high cost of obtaining lunasin from soy waste limits its use for nutritional interventions, soy flour does contain high concentrations of the peptide (depending on some genotype soy).

Its good see the diverse activities associated with Soy......

Source : http://pubs.acs.org/doi/abs/10.1021/jf803303k?prevSearch=Elvira%2Bde%2BMejia&searchHistoryKey=

First live targeting of tumors with RNA-based technology

Researchers at Duke University Medical Center have devised a way they might deliver the right therapy directly to tumors using special molecules, called aptamers, (Aptamers are oligonucleotides or peptide molecules that bind to a specific target molecule) which specifically bind to living tumor tissue.......

More....First live targeting of tumors with RNA-based technology