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The US Food and Drug Administration (FDA) announced on Monday that it had approved Afinitor oral tables (everolimus) for the treatment of advanced kidney cancer in patients where the disease continued to progress after treatment with other drugs.
Afinitor is manufactured by Novartis International AG of Basel, Switzerland.
Dr Robert Justice, director of the Division of Drug Oncology Products in the FDA's Center for Drug Evaluation and Research (CDER) said:
"Afinitor provides an option for patients with advanced renal cell cancer after failure of treatment with the cancer therapies sunitinib [Sutent, from Pfizer] or sorafenib [Nexavar, from Bayer]."
"Targeted cancer therapies like Afinitor have increased the number of months patients can live without the tumor progressing," he added.
The most common form of kidney cancer is renal cell carcinoma, which starts in the lining of the tiny tubules inside the kidney that clean the blood by filtering out the waste products of metabolism and other body processes. It accounts for about 2 per cent of all new cancers and rates of new cases are going up worldwide, partly because of smoking and obesity, according to sources cited in a Novartis press statement.
Renal cell carcinoma resists standards treatments like radiotherapy and chemo, and treatment usually starts with surgical removal of the affected kidney. If the cancer hasn't spread outside of the affected kidney, five year survival can be as much as 60 to 70 per cent, but it is much lower if the cancer has spread.
Afinitor is a kinase inhibitor: it stops tumors growing by blocking a specific protein called mTOR, the mammalian target of rapamycin. This action stops the cell to cell communications that help cancer cells to grow, divide and metabolize. In contrast, Sutent and Nexavar are multiple kinase inhibitors and work on several targets at the same time.
The FDA approval relied on the results of the RECORD-1 clinical trial that tested the safety and effectiveness of Afinitor given as a daily oral dose against placebo. The trial was stopped early because interim results showed that patients taking the drug experienced delayed tumor growth and spread compared to those who did not. Also, disease progression was delayed for about five months in 50 per cent of the patients who took the drug compared to only 2 months for those who did not.
According to the FDA announcement, the most frequent adverse reactions (1 in 5 patients had them) included: "inflammation in the mouth, loss of strength, diarrhea, poor appetite, fluid buildup in the extremities, shortness of breath, coughing, nausea, vomiting, rash, and fever".
Lab tests of blood samples also showed that at least half the patients were anemic, had low white blood counts, high cholesterol, high blood sugar and high triglycerides (blood fats), said the agency.
Dr Robert J Motzer, attending physician, Memorial Sloan-Kettering Cancer Center, New York and principal investigator of the trial told the press that:
"This approval provides a new and useful tool for treating advanced renal cell cancer, representing an important step forward in managing this disease."
"New treatment options are vital to help us continue to offer patients with advanced kidney cancer new ways to battle their difficult-to-treat disease. Based on clinical trial data, this option should be considered when sunitinib or sorafenib fail."
Novartis said in a press release that it has also filed for approval of Afinitor in the European Union, Switzerland and Japan, as well as with other regulatory agencies globally and that Phase III trials are underway to explore the potential of the drug in treating several other cancers.
David Epstein, President and CEO, Novartis Oncology, Novartis Molecular Diagnostics said:
"We continue to study Afinitor in kidney cancer, and through a broad clinical program to explore its potential in many other tumor types."
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A "danger receptor" that may kick-start an immune reaction to cancer in the body has been found by UK researchers.
It picks up signs of cell death caused by injury or tumours and mobilises the body's defences, Nature reports.
The finding may explain why some tumour-killing drugs partly work by setting off an immune response.
Better understanding of the receptor could help develop cancer treatments that harness the immune system, the London Research Institute team said.
Cell death is a normal process in the body which keeps growth and repair ticking over and keeps tissue healthy.
But sometimes there is an abnormal type of cell death called necrosis.
It has been thought for many years that the body somehow senses this abnormal cell death and sets off an immune reaction.
From an evolutionary point of view this would make sense as injury puts the body at risk of infection and an immune response would be a sensible precaution.
However, until now no receptor capable of detecting this abnormal cell death had been found.
The researchers discovered that the DNGR-1 receptor on a type of immune cell called a dendritic cell mobilises an immune response after coming across this abnormal cell death.
Dendritic cells act as messengers, alerting other types of immune cells to kill invaders, such as viruses and bacteria.
Trigger
The researchers said tumours could also trigger this type of immune reaction because they often contain clusters of cells undergoing this type of cell death as they have a limited blood supply.
Dr Caetano Reis e Sousa, lead author based at Cancer Research UK's London Research Institute, said: "After a 15-year hunt, we've identified the first 'danger receptor' - one which senses abnormal cell death and then triggers an immune response.
"The detection of 'danger' could explain some situations when a tumour triggers an immune reaction against itself."
He said manipulating this system could be beneficial in treating cancer but also in other areas, such as preventing rejection in organ transplantation.
"There is a theory that some cancer-killing drugs kill tumour cells in such a way that triggers the immune system against them so they have a double whammy."
Dr Lesley Walker, director of information at Cancer Research UK, said: "The concept of using the body's immune system to fight cancer has been around for decades, but advances in recent years have made this field of research a very exciting one.
"The results of this study are really important scientifically and a step towards understanding how to manipulate the immune system to treat cancer in the future."
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The first baby in the UK tested before conception for a genetic form of breast cancer has been born.
Doctors at University College London said the girl and her mother were doing well following the birth this week.
The embryo was screened for the altered BRCA1 gene, which would have meant the girl had a 80% chance of developing breast cancer.
Women in three generations of her husband's family have been diagnosed with the disease in their 20s.
Paul Serhal, the fertility expert who treated the couple, said: "This little girl will not face the spectre of developing this genetic form of breast cancer or ovarian cancer in her adult life.
"The parents will have been spared the risk of inflicting this disease on their daughter.
"The lasting legacy is the eradication of the transmission of this form of cancer that has blighted these families for generations."
Pre-implantation genetic diagnosis (PGD) involves taking a cell from an embryo at the eight-cell stage of development, when it is around three-days old, and testing it.
Using PGD to ensure a baby does not carry an altered gene which would guarantee a baby would inherit a disease such as cystic fibrosis, is well-established.
But in 2006, the Human Fertilisation and Embryology Authority said doctors could test for so-called susceptibility genes, such as BRCA1.
Everybody carries a version of these genes - in fact a properly functioning BRCA1 protein helps stop cancer before it starts - but some particular variations of the genes greatly increase the risk of cancer.
Increased chance
Carrying the key BRCA1 mutation in this family's case would have given the increased chance of breast cancer and 50% chance of ovarian cancer later in life.
The couple, who wish to remain anonymous, wanted to eradicate the gene flaw from their family.
The husband's grandmother, mother, sister and a cousin have been diagnosed with the disease.
If the 27-year-old woman and her husband had had a son, he could have been a carrier and passed it on to any daughters.
Josephine Quintavalle, of the campaign group Comment on Reproductive Ethics, said: "This is nothing personal towards the girl, but I think we have gone too far.
"Underlying all this is eugenics."
Dr Sarah Cant, of the charity Breakthrough Breast Cancer, said: "The decision to screen embryos to see whether they have a faulty breast cancer gene is a complex and very personal issue.
"Women with a family history of breast cancer tell us that what might be right for one person may not be right for another.
"It's important for anyone affected to have appropriate information and support so they can make the right choice for them."
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Testing a lung cancer patient's blood could help doctors predict the likely success of chemotherapy treatment.
UK scientists identified a molecule made by a more aggressive form of the disease, the journal Clinical Cancer Research reported.
Patients with this in their blood were less likely to respond to drugs, they said.
Cancer Research UK said the discovery could help doctors choose the right kind of treatment for patients.
Lung cancer kills more than 30,000 people in the UK every year, and survival rates have not improved alongside those for breast or bowel cancer in recent years.
There is more than one type of lung cancer, but the variety under investigation by Liverpool-based researchers, small-cell lung cancer, which accounts for between 15% and 20% of cases, is one of the more difficult to treat.
Even small cell lung cancer comes in different forms, with a version called "neuroendocrine" being the least likely to be treated successfully.
The researchers found that a molecule called SCG3 mRNA was more likely to be found in the blood of people with neuroendocrine small cell cancer.
In theory, if larger studies back this up, it could mean that patients arriving at the clinic could be tested to give doctors an idea of the likely success of therapy - or perhaps to predict when a patient was relapsing before other signs emerged.
No tests
It might also make it easier for scientists, when looking at new chemotherapy treatments in trials, to compare their effectiveness in different groups of small cell lung cancer patients.
Dr Judy Coulson, from the University of Liverpool, said: "There are currently no blood-based markers routinely used to monitor patients with this type of lung cancer.
"We found that SCG3 mRNA is an incredibly sensitive marker of these tumours and could be used to detect circulating tumour cells in patients with this disease."
Lesley Walker, from Cancer Research UK, said: "This discovery is an important step to understanding how to treat lung cancer patients more effectively.
"Lung cancer can be very difficult to treat in its later stages, either because it has spread or because there are too many tumours."
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An extract from grape seeds can destroy cancer cells, US research suggests.
In lab experiments, scientists found that the extract stimulated leukaemia cells to commit suicide.
Within 24 hours, 76% of leukaemia cells exposed to the extract were killed off, while healthy cells were unharmed, Clinical Cancer Research reports.
The study raises the possibility of new cancer treatments, but scientists said it was too early to recommend that people eat grapes to ward off cancer.
Grape seeds contain a number of antioxidants, including resveratrol, which is known to have anti-cancer properties, as well as positive effect on the heart.
Previous research has shown grapeseed extract has an effect on skin, breast, bowel, lung, stomach and prostate cancer cells in the laboratory.
It can also reduce the size of breast tumours in rats and skin tumours in mice.
However, the University of Kentucky study is the first to test its impact on a blood cancer.
Lead researcher Professor Xianglin Shi said: "These results could have implications for the incorporation of agents such as grapeseed extract into prevention or treatment of haematological (blood) malignancies and possibly other cancers.
"What everyone seeks is an agent that has an effect on cancer cells but leaves normal cells alone, and this shows that grapeseed extract fits into this category."
The researchers exposed leukaemia cells to grape extract in a range of different doses.
Apoptosis
One of the higher doses produced a marked effect, causing large numbers of the cells to commit suicide in a process known as apoptosis.
This is a natural method of getting rid of damaged and potentially dangerous cells.
When the mechanism behind apoptosis breaks down, cancerous cells can survive and multiply.
The researchers found grapeseed extract activates a protein called JNK which helps to regulate apoptosis.
When they exposed the leukaemia cells to an agent that inhibits JNK, the grapeseed extract effect was cancelled out.
Silencing the gene that makes JNK also blocked the extract's ability to kill cancer cells.
Kat Arney, Cancer Research UK's senior cancer information officer, warned against jumping to firm conclusions.
She said: "This is yet another story highlighting the potential cancer-fighting properties of naturally-occurring chemicals.
"Although interesting, it's still a long way from being a treatment that we can give to patients."
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Scientists from the National Cancer Institute (NCI), building upon earlier research, found in both mice and human breast tumor samples that a certain gene signature predicted the chance of metastasis. Many experts have believed that metastasis is primarily the result of non-inherited mutations in cancerous tissue.
"Our earlier studies clearly established that inherited factors also play an important role in metastatic progression and can help distinguish which tumors have a propensity to metastasize," study author Kent W. Hunter, head of the NCI's Metastasis Susceptibility Section in the Laboratory of Cancer Biology and Genetics, said in an NCI release. "Hopefully, in the future, we will be able to determine which women are more likely to have a tumor that would metastasize, and we could then tailor therapy specifically for them, avoiding the use of harsh treatments for those with a low probability of metastasis."
The researchers first discovered a gene signature in mice that raised the risk of breast cancer metastasis in mice by 20-fold. They then found the corresponding human gene signature, and it predicted relapse or recurrence in four of five breast cancer patients.
"Our study provides additional evidence of the role of inherited genes in human breast cancer progression," Hunter said.
The study was published in the Jan. 1 issue of Cancer Research.
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Improved Communication May Be Best Method to Prevent Mistakes
A new study shows that medication errors are common among children and adults taking chemotherapy drugs at home or in outpatient clinics.
Researchers reviewed records of nearly 1,300 patient visits at three adult oncology outpatient clinics and 117 patient visits at one pediatric facility between Sept. 1, 2005, and May 31, 2006.
They showed that 7% of adults and 19% of children taking chemotherapy drugs in outpatient clinics or at home were given the wrong dose or experienced other medication mistakes.
The study, published in the Journal of Clinical Oncology, calls for improved communication to cut down on errors it describes as "high" in adult and pediatric cancer patients.
Of the errors involving adults, 55 had the potential to harm the patient, and in 11 instances, harm was caused, the researchers say.
About 40% of the medication errors in children had the potential to cause harm, and four children actually were harmed by mistakes, the study shows.
In a news release, Kathleen E. Walsh, MD, assistant professor of pediatrics at the University of Massachusetts Medical School, says that as cancer care increasingly shifts to outpatient settings, the potential for errors goes up correspondingly.
More than 70% of errors in children occurred at home, says Walsh, the study's leader.
Examples of pediatric errors included giving the wrong amount of medication or giving it at the wrong frequency because of confusion about instructions.
The mistakes in adults included the administration of incorrect doses because of confusion over conflicting orders. Consequences of mistakes included patients being overhydrated prior to giving chemotherapy and abdominal pain in patients taking narcotics without treatment for constipation.
The researchers say more than 50% of errors involving adults were in clinic administration, 28% in ordering medications, and 7% in use of chemo in patients' homes.
Why Medication Mistakes Happen
"As cancer care shifts from the hospital to the outpatient setting, adults and children with cancer receive more complicated, potentially toxic medication regiments in the clinic and home," Walsh and colleagues write in the article.
According to the researchers, methods to prevent outpatient medication mistakes often fail because of a lack of recognition of errors, communication problems, and fragmentation of care.
Chemotherapy regimens outside of clinical settings are "particularly complex because of the intense monitoring required" and a plethora of potential problems made more likely when drugs are taken in a non-clinical setting, they write.
Preventing Medication Errors
"Information technology such as computer order entry, electronic medication administration records and bar-coding used to prevent errors in the inpatient setting may be particularly important in outpatient clinics where multiple oral and intravenous medications are administered, such as in an oncology clinic," the researchers contend.
One simple strategy to reduce errors: requiring that medication orders not be written until the day of administration, the researchers suggest.
Walsh says in the release that most errors involving children could be reduced "by better communication and support for parents of children who use chemotherapy medications at home."
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When researchers look inside human cancer cells for the whereabouts of an important tumor- suppressor, they often catch the protein playing hooky, lolling around in cellular broth instead of muscling its way out to the cells' membranes and foiling cancer growth.
This phenomenon of delinquency puzzled scientists for a long time until a cell biologist in the Johns Hopkins University School of Medicine felt compelled to genetically grab the protein by the tail and then watched as it got back to work at tamping down disease.
"It was curious that when we removed its tail, the protein suddenly was unhindered and moved out to the membrane and became active," says Meghdad Rahdar, a graduate student in pharmacology.
The discovery, published Dec. 15 online at the Proceedings of the National Academy of Sciences, represents a potential new approach to cancer therapy, according to Peter Devreotes, Ph.D., professor and director of cell biology at Johns Hopkins.
"A long-term goal is to find a drug that does the equivalent of our bit of genetic engineering," he says.
The flexible tail contains a cluster of four amino acids the building blocks of proteins that regulate this tumor suppressor known as PTEN. When chemically modified, these amino acids act to "glue" the tail back to the body of PTEN and prevent the attachment of PTEN to the membrane. By genetically removing PTEN's tail, or manipulating the cluster of four amino acids so that they cannot be modified, the researchers persuaded PTEN to move to the cell membrane where it goes about its tumor-suppressing business of degrading a molecular signal called PIP3 that causes errant cell growth.
"As far as I know, I haven't seen anyone activate a tumor suppressor, but we seem to have done it genetically," Rahdar says.
While genetically engineering cancer cells in the human body is neither practical nor safe, manipulating such unbinding of PTEN with drugs is a viable alternative to guard against cell overgrowth, the hallmark of cancer, the Hopkins scientists say.
In many tumors, PTEN is simply not present. In others, it's there, but a key enzyme that produces PIP3 is over-activated. The Hopkins team already has shown the first evidence that adding the modified PTEN to cells that lack PTEN not only restores normal enzyme levels but ramps up PTEN activity and quells the cell growth signal.
The research was supported by the National Institutes of Health.
In addition to Rahdar and Devreotes, authors on the paper are Takanari Inoue, Tobias Meyer, Jin Zhang and Francisca Vazquez, all of Johns Hopkins.
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Cancer is a term used for diseases in which abnormal cells divide without control and are able to invade other tissues. Cancer cells can spread to other parts of the body through the blood and lymph systems.
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start -- for example, cancer that begins in the colon is called colon cancer; cancer that begins in basal cells of the skin is called basal cell carcinoma.
Cancer types can be grouped into broader categories. The main categories of cancer include:
Carcinoma - cancer that begins in the skin or in tissues that line or cover internal organs.
Sarcoma - cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue.
Leukemia - cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of abnormal blood cells to be produced and enter the blood.
Lymphoma and myeloma - cancers that begin in the cells of the immune system.
Central nervous system cancers - cancers that begin in the tissues of the brain and spinal cord.
Origins of cancer
All cancers begin in cells, the body's basic unit of life. To understand cancer, it's helpful to know what happens when normal cells become cancer cells.
The body is made up of many types of cells. These cells grow and divide in a controlled way to produce more cells as they are needed to keep the body healthy. When cells become old or damaged, they die and are replaced with new cells.
However, sometimes this orderly process goes wrong. The genetic material (DNA) of a cell can become damaged or changed, producing mutations that affect normal cell growth and division. When this happens, cells do not die when they should and new cells form when the body does not need them. The extra cells may form a mass of tissue called a tumor.
Not all tumors are cancerous; tumors can be benign or malignant.
Benign tumors aren't cancerous. They can often be removed, and, in most cases, they do not come back. Cells in benign tumors do not spread to other parts of the body.
Malignant tumors are cancerous. Cells in these tumors can invade nearby tissues and spread to other parts of the body. The spread of cancer from one part of the body to another is called metastasis.
Some cancers do not form tumors. For example, leukemia is a cancer of the bone marrow and blood.
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