This Month's Clinical Focus: Oncology

 For many patients today, a cancer diagnosis no longer represents a death sentence.  Many types of cancer are achieving the status of chronic but treatable diseases. Earlier detection and better treatments are extending the lives of cancer patients as never before.

As Julia Rowland, Ph.D., director of the NCI Office of Cancer Survivorship, and her colleagues stated in a recent research journal: "In the last three decades, cancer has been transformed from a fatal disease to one in which the majority of people diagnosed with cancer receive highly effective treatments that result in either cure or long-term survivorship."

This message of hope is a hallmark of the latest advances in cancer research by NIH's NCI and the many NCI-funded researchers across the nation. (Source: NIH Medline Plus Magazine)

New Antibiotics May Target Cancer-Causing Proteins
Anti-cancer use of thiazoles could be possible, research suggests
 Scientists are closer to understanding how a recently approved class of antibiotics may work against cancer.

The drugs, called thiazole antibiotics, appear to block a cellular protein called FoxM1, one of the most over-produced proteins in cancer cells, according to researchers at the University of Illinois at Chicago College of Medicine. FoxM1 is believed to play an important role in causing cells to become cancerous and may present a promising target for future anti-cancer treatments.

The researchers also found that thiazoles may inhibit proteasomes, a molecular complex within cells that disposes of old proteins marked for destruction. Recently, a number of proteasome inhibitors have shown promise against cancer. One of these inhibitors, bortezomib (Velcade), has proven effective against a number of cancers, including myeloma and certain forms of lymphoma.

The new research, which appears in the online journal PLoS ONE, points to the possible anti-cancer use of thiazoles in the future. In a university news release, study author Andrei Gartel, an associate professor of molecular genetics, said that by using thiazole antibiotics in combination with well-known proteasome inhibitors, "we may see a synergy that allows us to markedly reduce the dose of any one of these drugs and still effectively kill the cancer cells."  (SOURCE: University of Illinois at Chicago, news release, Aug. 11, 2009)

Scientists kill cancer cells with "trojan horse"

 Australian scientists have developed a "trojan horse" therapy to combat cancer, using a bacterially-derived nano cell to penetrate and disarm the cancer cell before a second nano cell kills it with chemotherapy drugs.

The "trojan horse" therapy has the potential to directly target cancer cells with chemotherapy, rather than the current treatment that sees chemotherapy drugs injected into a cancer patient and attacking both cancer and healthy cells. Sydney scientists Dr Jennifer MacDiarmid and Dr Himanshu Brahmbhatt, who formed EnGenelC Pty Ltd in 2001, said they had achieved 100 percent survival in mice with human cancer cells by using the "trojan horse" therapy in the past two years.

The scientists plan to start human clinical trials in the coming months. Human trials of the cell delivery system will start soon at the Peter MacCullum Cancer Center at the Royal Melbourne Hospital and The Austin at the University of Melbourne. The therapy, published in the latest Nature Biotechnology journal, sees mini-cells called EDVs (EnGenelC Delivery Vehicle) attach and enter the cancer cell.

The first wave of mini-cells release ribonucleic acid molecules, called siRNA, which switch off the production of proteins that make the cancer cell resistant to chemotherapy. A second wave of EDV cells is then accepted by the cancer cell and releases chemotherapy drugs, killing the cancer cell. "The beauty is that our EDVs operate like 'Trojan Horses' They arrive at the gates of the affected cells and are always allowed in," said MacDiarmid. "We are playing the rogue cells at their own game. They switch-on the gene to produce the protein to resist drugs, and we are switching-off the gene which, in turn, enables the drugs to enter."

DISARMING TUMOUR CELLS
RNA interference, or RNAi, is designed to silence genes responsible for producing disease-causing proteins and is one of the hottest areas of biotechnology research. RNA was the basis of the 2006 Nobel Prize in medicine.

Dozens of biotechnology companies are looking for ways to manipulate RNA to block genes that produce disease-causing proteins involved in cancer, blindness or AIDS. Brahmbhatt said that after treatment with conventional drug therapy, a large number of cancer cells die but a small percentage of the cells can produce proteins that make cancer cells resistant to chemotherapeutic drugs. "Consequently, follow-up drug treatments can fail. The tumors thus become untreatable and continue to flourish, ultimately killing the patient," said Brahmbhatt.

"We want to be part of moving toward a time when cancers can be managed as a chronic disease rather than being regarded as a death sentence," he said. The Nature report said the mini-cells were "well tolerated with no adverse side effects or deaths in any of the actively treated animals, despite repeated dosing." "Significantly, our methodology does not damage the normal cells and is applicable to a wide spectrum of solid cancer types," said MacDiarmid. "The hope is that the benign nature of this EDV technology should enable cancer sufferers to get on with their lives and operate normally using out-patient therapy."
(Source: SYDNEY / Reuters 6/29/09)

Study traces steady declines in U.S. cancer deaths
 Improvements in cancer screening and better treatments have resulted in steady declines in cancer death rates over the past three decades.  The study uses a different way of looking at cancer death rates that measures improvements in cancer deaths by age.

They said younger adults -- those aged 35 to 45 years old -- have experienced the steepest declines in cancer death rates, but all age groups have shown some improvement. "Essentially, the younger you are, the faster your rates are declining," said Dr. Eric Kort of the Helen DeVos Children's Hospital in Grand Rapids, Michigan, whose study appears in the journal Cancer Research.

U.S. government estimates suggest there had been little improvement in cancer death rates throughout the 20th century, with rates only beginning to improve in the mid-1990s, Kort said. But that does not tell the whole story, he said.  "The way that these statistics are traditionally reported is they have averaged all of the age groups together to get a composite rate," Kort said in a telephone interview.

"The problem with that is because most cancer deaths occur in older Americans, the average heavily emphasizes the experiences of older people. It's like watching the caboose of the train to tell when the train is changing direction," he said.  Instead, Kort's team looked at improvements in cancer deaths among groups of individuals born in five-year intervals starting in 1925.  Using that method, Kort said, "Everyone born since the 1930s has enjoyed a decreased risk of cancer death, at every age."  People in the youngest age group -- those aged 35 to 45 -- had a greater than 25 percent decline per decade in cancer deaths, he said.

Kort said cancer prevention -- including smoking cessation efforts -- have played an important role in these trends.  "We're also benefiting in profound ways from progress we're making in early detection and better treatments. Some of these advances benefit younger people first," he said. 

In childhood cancers, advances in treatments for leukemia and lymphoma mean many more people can survive cancers that were once considered a death sentence.

And better screening for cancers that occur in older age, such as mammography in breast cancer and colonoscopy for colon cancer are spotting cancers at an earlier stage, when they are easier to treat.

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