What is the present state of the art in cancer treatment, and what are medicine's present limitations? What new advances may be in the pipeline?

Today's New York Times reports that an FDA advisory board is recommending approval of Provenge, a promising new therapy that would use a patient's own immune system to attack cancer cells:

Provenge was developed by Dendreon, a Seattle biotechnology company.

Approval of Provenge would open a new front in the war on cancer because its mode of action is different from that of existing drugs and radiation, which attack cancer cells directly. Provenge is a personalized therapy in which some of a patient’s white blood cells are removed, processed by Dendreon, then infused back into the body three or four days later.

Approval would also represent the first success after numerous setbacks in efforts to develop what are sometimes called cancer vaccines, not because they prevent cancer but because they harness the immune system to fight the disease after it develops.

Here's more:
Dendreon tested Provenge in men who had prostate cancer that had spread to other parts of the body and was no longer being controlled by hormone therapy, but was also not causing symptoms. Roughly 50,000 men in the United States are in this category, and they generally survive only a year or two, Dr. Christopher Logothetis of M. D. Anderson Cancer Center, a consultant to Dendreon, told the panel.

Only one drug has been shown to lengthen the lives of these men: the chemotherapy drug Taxotere, also called docetaxel, which has extended survival by about two and a half months. But it has severe side effects, and many men opt not to use it.

In its main trial, Provenge extended median survival by 4.5 months — to 25.9 months for the treated patients versus 21.4 months for those receiving a placebo. After three years, 34 percent of patients who got Provenge were alive compared with 11 percent of those who got a placebo. Provenge also had generally mild side effects like fever and chills, though there was some signs it could raise the risk of strokes.

Here's a link to Reuters Cancer News, a daily digest of information about new treatments. It's part of the OncoLink web site of the University of Pennsylvania's Abramson Cancer Center, which has a lot of great resources for anyone who wants to learn more about cancer.

From the American Society of Clinical Oncology, here's a link to Cancer Advances,a continually-updated portal on the latest in cancer research. It includes summaries of new studies published in the Journal of Clinical Oncology, research presented at ASCO's annual meeting, and patient briefings from cancer experts.

From the latest issue of Time magazine, here's an article entitled "How to Live with Cancer," which argues that

in recent years the treatment of what used to be dismissed as terminal cancer has shifted from a win-or-lose battle against acute illness to something more akin to managing a chronic disease — in many cases with extended periods of feeling just fine, thanks.

"To us it's a great sea change in the way people look at cancer," says Dr. Daniel F. Hayes, clinical director of the breast oncology program at the University of Michigan Comprehensive Cancer Center. Hayes says that he and fellow oncologists are enthusiastic about the example Edwards is setting. "From our standpoint, we spend a lot of time trying to make it clear that while cancer — especially metastatic breast cancer — won't just go away, you can still live a long and productive life with it."

The change in managing cancer reflects a series of hard-won improvements in treatment — not, alas, for every form of cancer, but particularly for breast, colon, prostate and even lung. The gains include an explosion of new drugs that are more targeted and less toxic than old-school chemotherapeutic agents. In addition, new tests are beginning to help doctors match drugs more precisely to the genetic and molecular makeup of an individual tumor. Finally, there are remarkable advances in managing the side effects of treatment, which, in the past, could be as debilitating as cancer itself.

The payoff is being seen in longer and better-quality survival. According to the American Cancer Society, the percentage of people living five years after a diagnosis of any type of cancer barely budged from 50% in the mid-1970s to 52% in the mid-'80s, but it shot to 66% for patients with a diagnosis after 1995 and is continuing to rise. For breast cancer patients the five-year survival numbers leaped, from 75% in the '70s to nearly 90% by 2002. Receiving a diagnosis of cancer — and seeing that cancer return — is always a terrible blow. But in fact, there is no better time to be living with the disease.

The article suggests that we're evolving from a view of incurable cancer as a death sentence to something more akin to the way that we now view HIV-AIDS--i.e., a chronic disease that can be mitigated and managed with the right treatment.

This New York Times article gives the best explanation of metastatic cancer that I've ever seen.

Also from the New York Times, Sloan-Kettering cancer center president Harold Varmus explains the most promising genetic approaches to fighting cancer. He ends with a hopeful assessment:

The genetic properties of newly diagnosed tumors, whether found through the screening of healthy people or after symptoms occur, also promise to be instructive. We already know that tumors that under the microscope are indistinguishable display important differences at the molecular level: different genes may be turned on or turned off, and different genes may be mutated. These changes are likely to help predict whether the tumor will invade, incite production of new blood vessels or spread; where it might spread; how quickly it might grow and threaten the patient’s life; and what treatments might be most effective.

These predictions will be especially important when tumors are found at very early stages — for example, after screening for prostate cancer with the P.S.A. test, for breast cancer with mammography or M.R.I.’s, or for lung cancer with CT scans. Current controversies about the significance and proper management of such tumors could be resolved with tests for molecular markers that accurately forecast a tumor’s behavior. The Food and Drug Administration has recently approved the use of a relatively simple test to assess breast cancers for their propensity to metastasize, by measuring the activities of 70 genes. While not yet perfect, such tests are welcome harbingers of a more rational basis for making crucial decisions about treatment.

These enhanced prospects for cancer care persuade me that the nation has invested wisely in the science of cancer. While we have succeeded in curing or controlling only a few advanced cancers, there is reason to believe that a new era of gene-based approaches to many cancers is at hand — especially if we have the political will to maintain the investment.

From Medical News Today, an Australian web site, here's a report on a new study with potentially huge implications:

Biologists at the University of California, San Diego have uncovered a new way by which common mutants of a critical human tumor-suppressing gene can promote tumor progression, a finding which may explain why some cancer treatments targeting human cancers with these mutants have proven ineffective.

Their discovery, detailed in a paper published in this week's early online issue of the journal Nature Cell Biology, also raises questions about the effectiveness of certain cancer therapies that may be unintentionally enhancing rather than retarding the progression of human cancers by expressing the mutated cancer-promoting tumor suppressor.

"Our findings could explain the resistance of human cancer cells expressing the mutants of this important tumor suppressing gene, p53, to current cancer therapies," says Yang Xu, an associate professor of biology at UCSD who headed the research team, which included Hoseok Song, a postdoctoral fellow at UCSD, and Monica Hollstein, a collaborator at England's University of Leeds.

Scientists have long known that the p53 gene is critical in suppressing the formation of tumors in the human body. Over the past 20 years, researchers have also discovered that when the p53 gene is mutated, which occurs in about half of all cancer cases, the p53 mutant protein not only loses its tumor suppressing properties, but can promote the progression of cancer and the resistance of cancer cells to drug therapies.

Here's more:
"Current cancer treatments, including radiotherapy and many forms of chemotherapy, kill cancer cells by inducing DNA double-stranded break damage in their genomes," says Xu. "Our findings could explain why cancer cells with p53 mutants are resistant to such therapies."

Here's an article from the National Cancer Institute web site, explaining the p53 gene and its significance in the development of cancer.

From HealthDay News, here's a story about a new American Cancer Society report that shows annual deaths from cancer dropped by 3,000 from 2003 to 2004, and that the death rate from all cancers has decreased by 13.6 percent between 1991 and 2004. (2004 is the most recent year for which data is available.)

We have been seeing a great deal of progress in terms of mortality rates and total deaths from cancer," said Elizabeth Ward, director of surveillance research with the American Cancer Society's department of epidemiology and surveillance research. "A lot of that progress has come about from public health intervention, including declines in tobacco-related cancer and declines in colorectal cancer mortality.

"A number of public health early detection and prevention programs that the cancer society and other groups have advocated are really making a difference," she added.


But the news isn't all good.

the cancer society is concerned that progress won't continue at the same pace as in recent years. Money spent on smoking-cessation programs has stopped increasing, and the decline in smoking has leveled off. In addition, the number of Americans getting screened for cancers, such as breast and colorectal malignancies, hasn't increased, Ward noted.

"Despite evidence that these programs are successful, they are not being sustained," she said.

Here's more, from theAmerican Cancer Society web site:

"Much of the suffering and death from cancer could be prevented by more systematic efforts to reduce tobacco use, improve diet, increase activity levels, and expand the use of established screening tests," says John R. Seffrin, PhD, national chief executive officer of the American Cancer Society. "But this report shows we may be losing momentum in some key areas that have been critical to our success."

The ACS in particular is worried about faltering efforts to curb cigarette smoking and other types of tobacco use, which causes 168,000 cancer deaths a year. Even after 40 years of anti-smoking efforts, smoking remains the single largest preventable cause of disease and death in the U.S.

Although smoking rates among both youth and adults began dropping in 1997, that decline appears to have stalled. Smoking rates among high school students did not change significantly between 2003 and 2005, the report says. Likewise, adult smoking rates were also basically unchanged from 2004 to 2005.

Higher tobacco taxes, restrictions on smoking in public places, counter-advertising, and coverage for quit-smoking programs and services are all effective means of curbing tobacco use. Unfortunately, funding for such programs falls far short of what is needed, the report says. For every $1 spent on tobacco control in the US in 2003, the tobacco industry spent $23 promoting products.

Another problem: more funding is needed for early detection cancer screening programs that reach people with low incomes or no insurance (though how will they get the treatment they need to stay alive?)

Yet another big problem: not enough is being done in the U.S. to fight obesity. Two thirds of Americans are overweight or obese, according to the report, and that makes them more vulnerable to cancer. One-third of U.S. cancer deaths are related to excess weight, poor nutrition, and lack of physical activity.

Here's a link to the full report, in case you want more information.

From Bloomberg, unfortunately, comes word of a study in which ImClone's new drug Erbitux failed to help pancreatic cancer patients live longer.

``There are reasons to think Erbitux works in pancreatic cancer, but the current results are not as dramatic as we hoped,'' said Alex Denner, who leads an executive committee that manages ImClone, in an e-mailed response. ``We remain committed to evaluating Erbitux in pancreatic cancer.''

That's sad news, because pancreatic cancer is one of the most lethal diseases a person can get. About 33,000 people die each year from it, and only 5 percent of pancreatic cancer patients are still alive five years after being diagnosed. Because the pancreas is small and deep inside the body, pancreatic cancer usually isn't discovered until a patient develops symptoms, by which time it's almost always too late to do much except try to slow the progression of the disease with radiation and chemotherapy. My father was diagnosed with it in late 2005, and he was dead 10 months later.

According to Science Daily, a new Wake Forest University study shows that stress hormone epinephrine causes changes in prostate and breast cancer cells that may make them resistant to cell death (and, ergo, treatment).

"These data imply that emotional stress may contribute to the development of cancer and may also reduce the effectiveness of cancer treatments," said George Kulik, D.V.M., Ph.D., an assistant professor of cancer biology and senior researcher on the project.

Here's more:
Kulik said the findings have several implications for patients and for researchers. "It may be important for patients who have increased responses to stress to learn to manage the effects," said Kulik. "And, the results point to the possibility of developing an intervention to block the effects of epinephrine."

Here's a Reuters article on two new studies that potentially may be huge in terms of finding genetic treatments for cancer.

Four genes gang up together to help cancer spread throughout the body, including one affected by arthritis drugs, researchers said Wednesday.

And a second study found that 87 different genes work to help make cancer more vulnerable to drug treatment.

Both studies published in this week’s issue of the journal Nature should help scientists develop more effective drugs to fight cancer, the second-leading cause of death in the developed world.

Here's more on the first study:

Dr. Joan Massague, a Howard Hughes Medical Institute investigator at the Memorial Sloan-Kettering Cancer Center in New York, and colleagues identified four genes that worked together to help breast cancer tumors spread to the lungs of mice.

The genes are called EREG, MMP-1, MMP-2 and Cox-2.

Massague’s team suppressed each gene one by one and found a small effect. “The remarkable thing was that while silencing these genes individually was effective, silencing the quartet nearly completely eliminated tumor growth and spread,” Massague said in a statement.

Further experiments showed just what the genes do to help the tumors spread.

The researchers injected cells lacking the four genes directly into mice. “When these cells reached the lung capillaries, they just got stuck there,” Massague said.

It appears that the cells use the four genes to break apart the walls of lung capillaries, get inside and start growing.

Here's the kicker...some existing drugs, used in combination, may be effective at silencing the genes.


Researchers have already noticed that people who use drugs that affect Cox-2, including aspirin, ibuprofen and the Cox-2 inhibitor Celebrex, have a lower risk of some cancers.

Celebrex, made under the chemical name celecoxib by Pfizer, and a cancer drug named Erbitux, made by Imclone Systems Inc. and Bristol-Myers Squibb Co. under the chemical name cetuximab, work against two of the four genes.

Massague’s team tested them together in the mice.

“We found that the combination of these two inhibitory drugs was effective, even though the drugs individually were not very effective,” said Massague. “This really nailed the case that if we can inactivate these genes in concert, it will affect metastasis.”

More on the second study:


A second team of researchers identified 87 different genes that, when turned down, helped certain chemotherapy drugs destroy tumors.

Michael White and colleagues at the University of Texas Southwestern Medical Center in Dallas screened practically the whole human genome to find the genes responsible for making lung tumor cells vulnerable to the cancer drug paclitaxel.

When they turned these genes down, they could kill cancer cells with paclitaxel, also known as Taxol, at doses 1,000 times lower than normally used.

When I hear about advances such as these, it makes me wonder if we actually may be able someday to cure cancer with genetic therapy.

This is really good news. According to News-Medical.net, Columbia University researchers have discovered a means of early detection for liver cancer, one of the most common and rapidly fatal human malignancies:

Using DNA isolated from serum samples as a baseline biomarker, the scientists examined changes in certain tumor suppressor genes that have been associated with the development of liver carcinomas. This is the first study to prospectively examine potential biomarkers for early detection of liver cancer in high-risk populations, including those with chronic hepatitis B and C virus infections.

Since most hepatocellular or liver carcinomas (HCC) are diagnosed at an advanced and usually fatal stage, the development of screening methods for early detection is critical. HCC is one of the most common and rapidly fatal human malignancies. Worldwide, the almost 500,000 new cases and nearly equivalent number of fatalities illustrates the lack of effective therapeutic alternatives for this disease.

The Mailman School researchers and colleagues studied the blood of patients enrolled in a cancer screening program in Taiwan, who provided repeated blood samples prior to diagnosis. A total of 12,000 males and over 11,900 females recruited in 1991-2 are being followed. Screenings performed by the team of Mailman School scientists found changes associated with cancer in serum DNA, presumably released from the tumor, one to nine years before actual clinical diagnosis.

From Science Daily, here's a glowing review of a new book, "Betty Crocker's Living with Cancer Cookbook: Easy Recipes and Tips through Treatment and Beyond."

Good nutrition is vital to people undergoing cancer treatment, yet treatment side effects can make eating seem unappealing. Now Betty Crocker, two oncologists, and a nutritionist bring back the joy of eating topeople undergoing cancer treatment with delicious recipes that are nutritious and easy to make. A thoughtful, practical gift for patients and families coping with cancer, the book includes: 130 recipes, from breakfasts and snacks to dinners and desserts, like Extra-Easy Baked Ziti, Fettuccine with Asparagus and Mushrooms and Country Blueberry Cobbler Advice from cancer patients, from coping with the emotional roller coaster to making recipes more appealing Recipes tagged to show which are helpful for the most common side effects of cancer treatment, plus special diet menus to help with them "Q and A" between Dr. Ghosh and cancer patients about how to handle the effects of cancer treatment An easy 7-day menu plan based on eating small meals six times a day -- just right for patients in treatment Cancer resource guide, nutrition and medical glossary "This book will be of great assistance to patients and families undergoing cancer treatment. It is a creative guide to the use of pleasant and easy menus to help alleviate difficult, commonly experienced side effects." andmdash;Dr. Barrie R. Cassileth, Chief, Integrative Medicine, Memorial Sloan-Kettering Cancer Center.

Here's a link to the Amazon.com page with more information about the book.

Also from Science Daily, a new study shows that cancer patients, who often must take an array of medications, are at high risk of having potentially harmful drug interactions.

Rachel Riechelmann, M.D., of the Princess Margaret Hospital in Toronto, and colleagues gave 405 cancer patients a questionnaire about the medications they had taken in the last four weeks. Their responses were analyzed using a drug interaction software program that could identify potential interactions and rank them by severity.

Nearly a third of patients were exposed to at least one potential drug interaction. The researchers identified 276 drug combinations with the potential to interact. About nine percent of the interactions considered of major severity--risk of death--and 77 percent of moderate severity--risk of serious health problems. About eight percent of the patients received duplicate medications.

The researchers found that some of the drugs interacted with anticancer medications. The most common were warfarin (a drug to prevent blood clots), antihypertension drugs, aspirin and anticonvulsants. Warfarin stood out because it can cause hemorrhages when used with certain chemotherapy medications, and the interaction can interfere with its metabolism. Additionally, patients with brain tumors were at particularly high risk since they are often prescribed anticonvulsants.

"We suggest that patients at high risk... be routinely screened for potential drug interactions. The development of medication databases and computerized physician medication order entry linked to screening electronic programs could help health professionals to identify dangerous drug combinations and monitor prescriptions of agents with high risks of interactions," the authors write.

Cancer patients may also be at risk because of medications that they can't take. During chemo, my father had to stop taking the medications that protected him against hypertension and blood clots. As a result, he suffered a massive stroke that ultimately killed him.

So far, the only studies are on mice, but even so, this is huge. Cancer Research UK reports:

A commonly used herbal supplement, triphala, can slow the growth of pancreatic cancer cells implanted into mice, according to research presented at the 2007 American Association for Cancer Research conference.

The study, conducted by scientists at the University of Pittsburgh Cancer Institute, found that an extract of triphala, the dried and powdered fruits of three plants, caused pancreatic cancer cells in tumours implanted in mice to die by a process called apoptosis.

This process, which is the body's normal method of disposing of damaged or unwanted cells, is often faulty in cancer cells.

Pancreatic cancer, as I've mentioned before, is one of the most aggressive and deadly cancers. Right now, there's no cure and very little that doctors can do even to slow it.

According to the Associated Press, Chinese oncologist Tony Mok Shu Kam thinks that traditional Chinese medicine can be combined with Western methods to treat cancer and other diseases more effectively.

Mok referred to ongoing studies in the United States and Russia that are examining the use of kanglaite, commonly used as a supplement in Chinese diets and one of the top-selling anti-cancer traditional herbs. Another Western-led study is looking at the herb astragalus, used in China to boost the immune system during chemotherapy.

Apparently, Chinese hospitals already are combining traditional Chinese and Western medicine--using herbs in conjunction with chemotherapy, for example. But Mok thinks more can be done to integrate the methods.

I found this tidbit interesting:

Mok also referred to a Chinese trial he was involved in this year in which some prospective patients declined to be part of a placebo control study to test the effectiveness of a traditional medicine when they learned their chances of getting the medicine were only 50-50. They preferred to go to a traditional doctor who would definitely prescribe the treatment they sought.

According to this article from CancerFocus, Irish oncologists have developed methods for treating lung cancer cells that have become resistant to new anti-cancer agents.

Led by Balazs Halmos, MD, hematologist/oncologist with the Ireland Cancer Center, the research team followed up on their previous study, published in the New England Journal of Medicine, which found that lung cancer cells can become resistant to novel targeted agents, such as Tarceva (erlotinib), a medication in widespread use for non-small-cell lung cancer (NSCLC). Tarceva is among a new generation of cancer therapies that disrupt the molecular target responsible for stimulating tumor growth. The drug targets the receptor for the epidermal growth factor protein (EGFRtermterm) to halt the spread of cancer cells. Clinical applications of the new drug initially yielded good results with approximately 10 percent of patients experiencing complete remission of their disease.

However, in spite of the therapy's initial success, patients inevitably suffered a relapse of their disease. Dr. Halmos' studies confirmed the existence of a mutation, and insertion of this mutation into test cells rendered them resistant to Tarceva. These cells became resistant by undergoing a miniscule molecular change in the EGFR protein that the medication targets. Further analysis revealed that the newly identified mutation was altering the protein's drug-binding pocket and thereby changing the "keyhole" so that the "key" – Tarceva – no longer fit. The researchers found that new second-generation Tarceva-like medications can overcome this change and such drugs are now in development, including in clinical trials at the Ireland Cancer Center.

This is big. According to CancerConsultants.com, researchers from Ohio State University and Italy have discovered a genetic test that may help in the early diagnosis of pancreatic cancer, one of the deadliest malignancies around.

The ability to accurately diagnose pancreatic cancer is crucial; accurate diagnosis allows pancreatic cancer to be treated as early as possible, which is necessary for optimal outcomes. However, physicians sometimes have difficulty distinguishing between chronic pancreatitis (inflammation of the pancreas) and pancreatic cancer. Methods that can more accurately identify these two conditions have been evaluated recently.

Researchers from Ohio State University and Italy recently conducted a clinical study to evaluate the effectiveness and accuracy of the expression pattern of miRNA in distinguishing between pancreatic cancer and chronic pancreatitis. miRNAs are molecules that help regulate gene expression. This study included 107 specimens from patients with either pancreatic cancer or chronic pancreatitis who underwent surgery between 2000 and 2005. The specimens underwent testing of miRNA expression patterns; these patterns were compared with the samples of pancreatic cancer, pancreatitis, and normal pancreatic tissue.

Expression of 23 miRNAs was able to differentiate between pancreatitis and pancreatic cancer with 93% accuracy.
Among patients with pancreatic cancer that had spread to lymph nodes, a subgroup of miRNAs was able to distinguish between long-term survivors and those who died within 24 months.
The researchers concluded, “Pancreatic cancer may have a distinct miRNA expression pattern that may differentiate it from normal pancreas and chronic pancreatitis. miRNA expression patterns may be able to distinguish between long- and short-term survivors, but these findings need to be validated in other study populations.”