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Nobel Winner Ralph Steinman Helped Patients with Cancer

Written by patrickmaguire on October 3, 2011

For apparently the first time in the history of the Nobel prize, one of its winners has died prior to receiving notification of the award. The Nobel Committee does not give posthumous (after death) awards. Sadly, Ralph Steinman, a Canadian born scientist honored for his pioneering work in understanding the human immune system, died prior to learning of his award, according to his family: http://www.google.com/hostednews/ap/article/ALeqM5iklEU6iZQNaX81iXFqOQBJgG3ttQ?docId=5dd680b1d7dd4e8bbd5996775080ea24. The scientist apparently actually used dendritic cell therapy (for which he received the Nobel) to treat the pancreatic cancer that ultimately caused his death.

When the human body is attacked by microscopic foreign invaders like bacteria, viruses, cancer cells, etc, it kicks into action for our protection. One component of that response is called innate immunity, which is when our immune cells attack microbial invaders without recognizing a specific antigen. Innate immunity is like an initial shotgun blast at all the bad guys. The other type of immune response, called adaptive immunity, takes some time to occur because it’s targeted at specific antigens. Adaptive immunity is like a targeted missile. 

During the process of adaptive immunity, specific cells within the body present the foreign antigen. These are called dendritic cells and they’re the main discovery for which Raplh Steinman received his Nobel.

Over the past 10-20 years, dendritic cell therapy has taken off as a type of anti-cancer treatment in the field of immunotherapy. One example of this type of technology is the new blockbuster drug for incurable prostate cancer called sipuleucel-T (brand name is Provenge). We’ve discussed Provenge in past blogs: http://thecancermd.com/blog/page/4/.

For men whose prostate cancer has already spread outside of the prostate gland and is no longer responding to standard treatment with anti-male hormone therapy, sipuleucel-T has proven to extend their survival. The process involves taking blood from the patient to isolate their dendritic cells, which are then combined with a protein found on prostate cancer cells. This combo is then injected back into the patient where the immune system recognizes the compound loaded with antigen. 

Basically, the patient’s own immune system then goes to work destroying the now well-recognized prostate cancer cells.

Because of Mr. Steinman’s lifelong work with dendritic cells and the adaptive immune system, tens of thousands of people will have lives that are longer and/or of better quality despite major illnesses. His Nobel prize is clearly well deserved!

- Patrick Maguire, MD

Posted in Cancer Treatment, Diagnosis, & Staging | Tagged cancer, death, dendritic, immune, Nobel, Provenge, steinman

Provenge and Intratumoral Chemo for Pancreatic Cancer

Provenge

Provenge is a treatment for asymptomatic or minimally symptomatic, metastatic, castrate-resistent (hormone refractory) prostate cancer. The mets can only be bone or soft tissue, and the patient can't be on narcotics for cancer-related pain. The patient must have had no chemo in the previous three months or steroids in 28 days, and must have an ECOG status of 0-1 (e.g., generally feels okay). According to Dendreon and research studies, Provenge is the only prostate drug to extend survival for this particular type of prostate cancer beyond two years. It is also the first FDA-approved immunotherapy vaccine.

Intratumoral Chemo for Pancreatic Cancer
At Cancer Treatment Centers of America in Tulsa, where appropriate, an endoscopic ultrasound (EUS) is used to reach the pancreas and inject chemotherapy directly into the tumor. This procedure is done once a week for four weeks, with a CT scan completed before the first treatment and after the final one to gauge results. Pancreatic intratumoral chemotherapy is an adjuvant treatment, so patients can still receive normal chemotherapy, treatment, etc., while receiving this procedure.

http://www.hopenavigators.com/tipping-the-scales/cutting-edge-technology/provenge-and-intratumoral-chemo-for-pancreatic-cancer

Managing Sleep Disorders in Cancer Patients

By Jill Delsigne

Continuous positive airway pressure machines help patients with sleep apnea breathe. Mask sizes and shapes vary and may cover the patient’s nose only or the nose and mouth. Cancer patients, especially those who have had maxillofacial surgery, may have difficulty finding the mask and system that work best for them.

Quality sleep is essential to healing, to proper immune function, and even to mental health. Conversely, lack of sleep has been associated with depression, anxiety, and decreased cognitive function. In cancer patients, poor sleep reduces quality of life; nevertheless, most cancer patients do not mention sleep problems unless explicitly asked.

Estimates of the percentage of cancer patients affected by sleep disorders range from 30% to 88%. Sleep apnea is more common among cancer patients than in the general population, and cancer patients are twice as likely as people without cancer to experience insomnia.

The restless nights caused by sleep disorders can impair patients’ quality of life, immune systems, cognitive abilities, and abilities to function day to day. “Patients often say they feel like different people when they lose sleep; they struggle with poor concentration and memory,” said Dave Balachandran, M.D., an associate professor in the Department of Pulmonary Medicine at The University of Texas MD Anderson Cancer Center. “Daytime sleepiness affects their ability to function, affecting every aspect of their lives.” These effects can last far beyond treatment, becoming a chronic condition. Some breast cancer survivors, for example, have had sleep disorders up to 10 years after finishing treatment.

Despite the pervasiveness of sleep disorders in cancer patients, not much research is available on the relationship between cancer and sleep. MD Anderson researchers are leading the development of this field with the world’s first sleep center dedicated to cancer patients. At the sleep center, Dr. Balachandran and his colleagues are exploring the relationship between cancer and sleep, particularly whether conditions such as insomnia and sleep apnea are contributing factors to cancer development, symptoms of disease, or side effects of treatment. The researchers also are developing sleep disorder treatments tailored to cancer patients.

Sleep apnea

Sleep apnea has recently been shown to have a strong correlation with death from cancer. This is not surprising when one considers the prevalence of sleep apnea among cancer patients. Research done by Carmen Escalante, M.D., chair of the Department of General Internal Medicine, and Ellen Manzullo, M.D., a professor in the department, found that almost 30% of patients reporting cancer-related fatigue were diagnosed with sleep apnea.

Sleep apnea can result from several types of cancer treatment. Up to 80% of patients with head and neck cancer suffer from sleep apnea as a comorbidity or as a result of surgery or radiation therapy, according to the research of Saadia Faiz, M.D., an assistant professor in the Department of Pulmonary Medicine. Patients with breast cancer are particularly vulnerable to sleep apnea related to weight gain, which is a common side effect of breast cancer treatment. Narcotics and sleep medications given to relieve symptoms of any type of cancer also can contribute to sleep apnea.

Sleep apnea may accelerate cancer progression or interfere with cancer treatment. In vitro and animal studies have shown that intermittent hypoxia, mimicking the effects of the recurrent airway obstruction characteristic of sleep apnea, causes cancer cells to be more likely to proliferate.

Because sleep apnea is common in cancer patients, patients who report excessive sleepiness should be evaluated by a sleep specialist. If sleep apnea is a possible culprit, the patient may need to undergo polysomnography, an overnight test that monitors breathing, sleep stages, rapid eye movement, and other sleep metrics.

The standard treatment for sleep apnea is the continuous positive airway pressure (CPAP) machine. The CPAP technicians at MD Anderson’s sleep center specialize in helping cancer patients find the mask and system that work best for them. Patients with head and neck cancer, for example, may need an adjusted mask if the standard air pressure will interfere with a surgery site. Other strategies are employed to make CPAP tolerable for patients with dry mouth as a result of chemotherapy or radiation therapy. Tailoring CPAP therapy to patient-specific needs has enabled CPAP patients at the sleep center to consistently use their masks and sleep through the night, at a compliance rate well above the 50% compliance rate in the general population.

Insomnia

Insomnia, the most prevalent sleep disorder in the general population, also affects up to 80% of cancer patients. According to an MD Anderson study, 60% of patients who reported cancer-related fatigue were diagnosed with insomnia. Clinically, insomnia is diagnosed by the following criteria: taking more than 30 minutes to fall asleep or waking for more than 30 minutes during the night, having difficulty conducting daytime functions, and experiencing these disturbances at least 3 nights per week.

The psychological stress of a cancer diagnosis can cause patients to lose sleep, as can schedule changes brought about by treatment. Patients requiring drug or radiation treatments at odd hours, for example, may find it extremely difficult to maintain a consistent sleep schedule.

The pain and other symptoms of the cancer itself and side effects of treatment—such as nausea, incontinence, or hot flashes—can also prevent patients from sleeping. In addition, medications to relieve other symptoms or to treat cancer can cause insomnia as a direct side effect. Inflammation, often the result of various types of treatment and of the cancer itself, also has been shown to affect the ability to sleep.

Radiation therapy, especially to the brain, can interfere with patients’ circadian rhythms and REM sleep cycles, inhibiting the signals for wakefulness and sleepiness. These signals are regulated by environmental cues known as zeitgebers. Zeitgebers include light, a regular meal schedule, social interactions, and daytime activity.

Treatments such as light therapy and stimulant therapy can help regulate circadian rhythms and establish a regular sleep-wake schedule for patients with insomnia. Sleep medications are often given to treat insomnia in cancer patients, especially those with advanced disease who are near the end of life. However, sometimes sleep medications are contraindicated because of potential adverse drug interactions. And, according to Dr. Balachandran, sleep medication is at best a short-term solution. When possible, he prefers to help patients develop healthy sleep behaviors that will benefit them in the long term.

Cognitive behavioral therapy, considered the standard of care for insomnia in the general population, has also shown great promise for cancer patients. Cognitive behavioral therapy has been shown to help 70%–80% of patients in the general population who receive it and to reduce by half the need for sleep medications taken by cancer patients.

Cognitive behavioral therapy has multiple components—stimulus control, sleep hygiene, relaxation, and others—that can be tailored to a patient’s needs. People with insomnia often respond well to stimulus control therapy, which reconditions them to associate their bedrooms only with sleep. As patients learn healthy sleep hygiene (for instance, developing a relaxing bedtime ritual; getting up if sleep is difficult and only returning to bed when sleepy; and controlling environmental factors such as light, temperature, and noise), sleep comes to them more easily. Progressive muscle relaxation and guided imagery are often also very effective.

Depending on the severity of the insomnia, patients can work individually with a psychologist or sleep specialist, participate in group therapy administered by a trained nurse or counselor, or self-administer cognitive behavioral therapy.

Self-administered cognitive behavioral programs geared toward a general population are currently available online and on CD, and researchers are working on developing a tablet application for cancer patients that will guide them through self-administered cognitive behavioral therapy. “This application will take into account the unique issues and challenges that cancer patients face,” Dr. Balachandran said, “and the platform will make this type of therapy widely accessible.”

Helping patients find help

Because quality sleep is essential to health and to recovery, several researchers have suggested that doctors ask cancer patients about sleep and fatigue at each medical visit and include sleep evaluation as part of the long-term follow-up. Patients often do not self-report these symptoms. In many cases, cancer patients with insomnia can benefit from referral to a psychologist or a sleep specialist.
For more information, contact Dr. Dave Balachandran at 713-563-4259. 

What is Proton Therapy?

Do Nutritional Supplements Help Prevent Cancer?

For many people, the risks may outweigh the benefits
Forty-five percent of American men and 55% of American women take nutritional supplements to prevent cancer and other serious health conditions. While some supplements have proven to be effective treatments for some medical conditions, the benefits of others are not scientifically proven, and a few have actually been proven dangerous when taken in excess.

The U.S. Food and Drug Administration (FDA) categorizes nutritional supplements under the general umbrella of foods rather than drugs. Unlike drugs, which cannot be marketed until they have passed clinical trials and a rigorous approval process, foods and nutritional supplements cannot be removed from the market by the FDA unless they are proven to be dangerous or have false label information. Although supplement manufacturers are required to list all active ingredients on their products’ labels and follow FDA manufacturing guidelines, the supplements do not have to be proven safe or effective.

Possible dangers

Because Americans tend to get enough of most vitamins in their normal diet, taking extra vitamins can cause an overdose; in 2008, more than 69,000 cases of toxicity due to a vitamin overdose were reported.

For example, taking more than 7.5 mg/day of vitamin A can lead to headaches, irritability, anoxia (lack of oxygen to the tissues), dry or cracked skin, and osteoporosis (reduced bone density). This harmful dose is available over the counter in many stores.

Another danger of supplements is that some can interact with some medicines in ways that harm the patient. People taking prescription medications should inform their health care team about any nutritional supplements they are taking.

In some studies, certain vitamins have also been associated with promoting cancer. One trial of selenium for the prevention of prostate, lung, or colon cancer recurrence was stopped because men who took 200 μg of selenium per day (12 times the recommended dose) had a higher recurrence rate than patients who did not take the supplement.

The vitamin D debate

Vitamin D and its effects on cancer have recently received a lot of attention in the media, but scientists have not reached a consensus about the effectiveness of vitamin D supplements for preventing cancer.

In a study currently under way, thousands of healthy men and women who take vitamin D and/or fish oil supplements will be examined at regular intervals for 5 years to determine the benefits of these supplements for preventing cancer and cardiovascular disease. Secondary goals of the study are to observe whether the supplements affect cognitive problems, diabetes, hypertension (high blood pressure), autoimmune disorders, bone fractures, mood disorders, or infections.

Nutrients in foods

An apple a day may really keep the doctor away. Fruits and vegetables contain important nutrients and fiber, which helps protect against colon cancer.

Studies have shown that eating fresh fruits and vegetables also reduces both the risk and recurrence rate of breast cancer. For example, women with BRCA1 gene mutations have a lifetime breast cancer risk around 60%, but one study found that the risk dropped to less than 30% when these women included a large variety of produce in their regular diet.

Another study showed that women who regularly ate mushrooms had a breast cancer risk about two-thirds lower than those who did not, and those whose daily diet included both mushrooms and green tea had an even lower breast cancer risk.

In 2010, the American Institute for Cancer Research estimated that a third of the cancers that occur every year in the United States could be prevented by lifestyle changes, including eating more whole foods.

The reason whole foods are more beneficial than vitamin supplements is probably that whole foods contain many nutrients that work synergistically to protect against cancer. Salmon, for example, is superior to salmon oil supplements because although both provide fatty acids, salmon provides nutrients not found in oils, such as vitamins D and B, amino acids, calcium, and selenium.

Foods known or believed to help prevent cancer include:

all berries grapes tomatoes mushrooms green tea salmon squash

broccoli cauliflower cabbage brussels sprouts linseed flaxseed

Physicians sometimes prescribe supplements to treat certain medical conditions, but for most people, a diet that includes healthful foods can eliminate the need for supplements. Bon appétit!

– J. Delsigne

For more information, talk to your physician, visit www.mdanderson.org, or call askMDAnderson at 877-632-6789. If you are a current MD Anderson patient and would like to consult a registered dietician, call 713-563-5167. 

Advances in Gene Mapping Technology May Accelerate Cancer Drug Development

Dr. Alexei Protopopov, an associate director at the Institute for Applied Cancer Science, demonstrates a DNA sequencing machine. Technological advances have reduced the time and cost of sequencing a human genome, improving researchers’ ability to develop experimental drugs that target cancer-causing mutations.

By Bryan Tutt
As new technology makes DNA sequencing faster and less expensive, researchers aim to exploit these abilities to develop novel targeted cancer therapies.

“It took about 10 years to get the first human genome sequenced,” said Giulio Draetta, M.D., Ph.D., a professor in the Department of Genomic Medicine and the director of the Institute for Applied Cancer Science at The University of Texas MD Anderson Cancer Center. “When the Human Genome Project’s work was conducted in the 1990s, they had huge rooms with sequencers, one next to another—these machines read along the DNA sequence to be able to divine the nucleotides that emerged; these nucleotides were then assembled together.” Systems are now available that can sequence a human genome in less than a week with a single machine, and even faster machines are being developed.

Genetic information and cancer

The information obtained from DNA sequencing is affecting cancer research in three main areas, according to Dr. Draetta.

First, mutations that affect cancer cells’ sensitivity to treatment have been identified. “Some emerging treatments are based on mapping the genome to look for mutations that respond to certain drugs,” Dr. Draetta said. For example, the melanoma drug vemurafenib specifically targets the BRAF V600E mutation and is approved by the U.S. Food and Drug Administration for the treatment of melanomas with such mutations. And non–small cell lung cancers with particular mutations to EGFR are sensitive to gefitinib and erlotinib. Second, genetic information has revealed common themes in cancer cells that explain their resistance to treatment. “Most tumors inactivate certain mechanisms that induce cell death. The tumors tend to survive even if you bang them with radiation therapy or chemotherapy,” Dr. Draetta said. “We can develop all sorts of therapies, but there is resistance because tumors don’t want to die. Now, at the genome scale, we know that these mechanisms that induce cell death are the predominant mechanisms of resistance that we have to deal with.”

Finally, DNA sequencing has revealed a greater extent of heterogeneity among cancer genomes than was once thought. A recent paper in the New England Journal of Medicine (2012; 366:883-892) described different mutations found in biopsy specimens from primary tumors and different metastatic sites in the same patients. The implication of this finding is that an agent that targets a specific mutation might be effective against a patient’s primary tumor but ineffective against metastases.

“The idea had always been that a tumor originates from a single mutated cell and that as it expands every cell in the tumor is the same. The reality is that cancer cells keep mutating as they move around the body,” Dr. Draetta said. “This makes the task of curing cancer daunting, but I like to believe that knowledge is power. The countermeasure to this problem of heterogeneity is to find commonality. The more we learn about the complexity of tumors, the more we can look for common themes or a common root cause.”

A new approach to drug development

DNA sequencing technology is a contributing factor to what Dr. Draetta described as a paradigm shift in the approach to drug development. This new research paradigm seeks to bridge gaps that are not always addressed, or are not addressed quickly, by academic research centers and pharmaceutical companies working separately.

“The more we learn about the complexity of tumors, the more we can look for common themes or a common root cause.”

– Dr. Giulio Draetta

“Academic institutions have traditionally pursued research on an individual basis. A particular scientist might be interested in curing a particular disease—and once the scientist has published reports, pharmaceutical companies have developed drugs based on the research,” said Dr. Draetta, who has led research laboratories in both settings. He pointed out that the traditional approach makes it difficult for pharmaceutical companies to invest in research for therapies that target a specific mutation found in a small subset of cancer patients.

“Drugs like blood pressure medication, which many patients may take every day for 20–30 years, are profitable for pharmaceutical companies and enable them to invest in research,” Dr. Draetta said. “But the companies have realized that they are not going to make that kind of money with a single targeted oncology drug because the complexity of cancer makes it unlikely that a single drug will be used to treat a large number of patients.”

At MD Anderson’s Institute for Applied Cancer Science, research teams work to identify targets for new drugs and then develop the drugs themselves. So far, the institute has about 70 research professionals from such fields as medicinal chemistry, pharmacology, genomics, bioinformatics, biology, and biochemistry. These professionals are divided into eight teams that work simultaneously on different aspects of multiple projects.

Dr. Draetta said the ability to quickly sequence a cancer genome makes the collaboration between work groups possible. “We can immediately go back and look at gene databases and ask, ‘Is this gene really altered? Which subtype of breast cancer is it? Can we find cancer cell lines that carry this alteration?’ Then we can study those cell lines and make sure there is dependency on the mutation,” he said. Dr. Draetta explained that the fact that a gene is amplified does not mean that the cancer needs it to survive. The cancer may have needed the mutation at one point, but additional mutations can make the first mutation redundant. Genomic information helps identify such mutations as unlikely therapeutic targets before drugs are developed.

“Each team is working on a specific time line to make sure a drug candidate’s mechanism of action is valid before it goes to clinical trials,” Dr. Draetta said. “The idea is to make sure there are no obvious mechanisms of resistance to a particular agent so that we invest our energy in developing the drugs that have the most potential.” Drug candidates that are validated early can be developed and brought to preclinical and clinical trials. “If we can find even small populations of patients who will benefit from a drug, we will bring it forward. Of course, we want to help as many patients as we can, are not driven by how many vials of a drug we can sell.”

Not only do the institute’s research teams coordinate with each other, they also work closely with other researchers and clinicians at MD Anderson. For example, Dr. Draetta regularly consults physicians in the Department of Investigational Cancer Therapeutics to determine what drugs currently in clinical trials are likely to become the standard of care that might be given along with a drug he is developing for a particular type of cancer.

Dr. Draetta sees this ability to bring together all aspects of research as a unique advantage of the institute’s location at a major cancer center. “I worked in the pharmaceutical industry for many years. My teams identified many compounds and developed them on our own, but we missed the ability to go back and open a dialogue with the biologists who did the initial re search,” Dr. Draetta said. “Now, we are engaging biologists and clinicians early on.”

Genomic information can also identify which patients are most likely to benefit from a drug. “We’re seeing in clinical trials that if you match the therapy with the mutation, you get much better results,” Dr. Draetta said, adding that matching therapy to mutations also can spare patients from unnecessary treatment.

“I’m very enthusiastic about this new research model,” Dr. Draetta said. “We want to use bioinformatics—computational tools—to look at common points of attack. It’s about working together and coordinating the effort.”
For more information, contact Dr. Giulio Draetta at 713-792-6803. 

Benefits of In-Person Support Groups

Face-to-face contact helps people cope with chronic illness
Support groups help people connect with others going through similar health situations. Support groups also serve as discussion forums for people with chronic illnesses as well as their family members or other caregivers. Sharing experiences with people who have a common illness often helps relieve the emotional stress associated with a chronic disease.

Unlike online or telephone support groups, in-person support groups allow members to communicate with more than just words. Stephen Collazo, a social work counselor in the Department of Social Work at The University of Texas MD Anderson Cancer Center, said he often sees support group members express sympathy with a look, nod, or furrow of the brow. “And that’s different from just typing, ‘I feel sorry for you,’” he said.

Face-to-face meetings can help group members develop personal connections that are more difficult to establish in online groups, according to Marisa Mir, a program coordinator with the Anderson Network, which is a program of the Department of Volunteer Services. “Some people need visual responses more than others,” she said. “They want to see other people and be able to connect with them.”

A typical in-person support group session can have about 10 people and lasts an hour. Most support groups are led by a social worker, counselor, or other health care professional who guides the group through a discussion. Social workers are trained to help group members process ideas or emotions together so that the members benefit from each other’s experiences.

Types of support groups

The two most common types of in-person support groups are open and closed groups. Open support groups are not limited to a predetermined number of sessions, and people are not required to register beforehand. Discussion topics in open support groups usually are decided by the group members. The group leader then asks open-ended questions and guides the discussion to help the members overcome whatever emotional or coping issues they have. Many patients attend open group sessions to listen to other people’s experiences or to share their own. “It’s very therapeutic and beneficial for them,” Mr. Collazo said. “There’s a lot of value to patients’ being able to tell their story and then hear other group members say, ‘We understand what you are going through, and we get it. You are not alone in this, and you are not weird for having these thoughts.’”
Unlike an open support group, a closed support group can be restricted by the number of sessions or when members can join the group. Moreover, closed support groups usually require people wanting to attend the sessions to register with the group leader. Most closed support groups are highly structured, and social workers often can provide focused clinical counseling to the group members.

Some open support groups are focused on educating group members about their illnesses and concerns. In such groups, a speaker (usually a doctor, nurse, or other health care professional) is brought in to talk about some aspect of the illness in the first half of the session, and the group leader guides a discussion about the topic in the second half.

Some support groups are for patients’ families rather than the patients themselves. One such group at MD Anderson is CLIMB (Children’s Lives Include Moments of Bravery), a support group for children who have parents with cancer. “You see the kids come in, and they don’t really know each other. You help them break down those barriers to build cohesion, and you start to work on processing questions like, ‘What does it mean that my mom has cancer?’” Mr. Collazo said. “Seeing these little kids open up is fascinating. It’s really interesting seeing the group transform from people who don’t know each other into a supporting element for each other.”

Benefits of support groups

There’s more to support groups than just the “feel-good” aspect. Research has shown that people with chronic illnesses and inadequate social support have worse health outcomes than those who have adequate emotional and psychological support. Support group members can build connections and gain such support through interactions with each other.

If you are affected by a chronic illness and are looking for a support group, your physician might be able to provide information about support groups in your area. Nonprofit groups like the American Cancer Society and the American Liver Foundation also may have information about local support groups.

– M. Sala

For more information, ask your physician, visit www.mdanderson.org, visit the Anderson Network at www.mdanderson.org/andersonnetwork or www.facebook.com/AndersonNetwork, or visit healthfinder.gov/FindServices/SearchContext.aspx?topic=833.