Scientists Attempt to Widen Range of Targeted Cancer Drugs

The development of new chemotherapy drugs that target cancerous tumor cells – while leaving healthy cells alone – has been a breakthrough in the cancer treatment field. However, these treatments have been shown to work only on a select few patients. Even when they do work, the tumor can create a resistance to the drugs, leaving the patient with fewer options. Several scientific research teams are working on new drugs that will work with a wider range of patients and target tumors before they can develop a resistance to the treatments.

The main component in the research behind these new cancer drugs comes from a deeper knowledge of how cancer cells come into being, grow, multiply and spread throughout the body.  One study at the Massachusetts Institute of Technology examines lung cancer cells and how scientists can synthesize drugs that can target the tumors.  The treatments can also be modified to help the patient as they proceed through the chemotherapy routines.

The MIT study takes a close look at a class of drugs known as “epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors”. Tyrosine kinase is a protein that functions as an “on/off” switch for many cell functions. When the proteins that regulate cell growth are permanently set in the “on” position, the cells can grow quickly and in uncontrolled ways, a common occurrence in cancer cells. Tyrosine kinase inhibitors act to slow down or stop the wild cell growth and stabilize or reduce the size of lung cancer tumors.

EGFR inhibitors are effective in less than 40 percent of all lung cancer patients. The drug’s effectiveness varies widely based on the patient’s medical history, smoking habits, race, gender and ethnicity. Dr. Philip Sharp, Professor at the Koch Institute for Integrative Cancer Research at MIT, said that laboratories around the world have “hundreds of drugs” that are in various stages of testing and development. “To personalize cancer care, we must interpret changes in (tumors) to predict the correct drug combination to use.”

Another factor in customizing cancer treatments is that some patients carry a mutation in the gene for EGFR, which makes the drugs more effective. The MIT study examined the differences between those patients and patients that did not respond to the drug. MIT researcher Doug Lauffenburger, along with a team of researchers, developed mathematical models to simulate the behavior of different types of cancer cells. The models revealed that the cancer cells that responded to the drug had a slower uptake of EGFR than the less responsive tumors.

While these methods require further verification, scientists are hopeful that the findings can lead to a possible screening test for lung cancer patients to determine the effectiveness of EGFR inhibitors in individual cases. Lauffenburger and his team also learned that the EGFR inhibitors could be more effective in certain cases when combined with another class of chemotherapy drug known as MEK inhibitors, which are often used to treat melanoma. In terms of tailoring drug combinations to individual patients, Dr. Sharp remarked that these findings “indicate that this is beginning to become possible.”

Sources: Technology Review,

Daily Aspirin May Lower Risk for Cancer

The simple act of taking aspirin once a day may dramatically reduce an individual’s likelihood of dying from cancer, according to a study conducted at the John Radcliffe Hospital in Oxford.

The primary focus of the Oxford study was to look at how aspirin affects death rates associated with stroke and heart attack. However, the team also decided to look at how many patients involved in the study eventually died from cancer. Remarkably, a comparison of patients given around 50 mg of aspirin daily and patients given a placebo shows that those given aspirin were 21 percent less likely to die from cancer.

This percentage is based off the participation of 25,570 patients that took part in eight different aspirin-related trials. Each trial lasted for four to eight years. Of all patients who took part in the study, 674 eventually died from cancer.

Interestingly, cancer death rates remained low for aspirin-taking patients long after the trials were completed. Five years after the trials, cancer-related deaths were 35 percent lower for all types of cancer and 54 percent lower for gastrointestinal cancers. After a full 20 years after the completion of the study, results show that aspirin-taking participants still displayed a 20-percent reduction in cancer deaths.

The study also shows that the positive effects of aspirin in relation to cancer take several years to show a measurable advantage. Specifically, it is estimated that aspirin must be take every day over a five-year period to reduce the probability of being diagnosed with lung, brain, pancreatic and esophageal cancers. Positive effects related to stomach and colorectal cancer require ten years of daily intake and prostate cancer requires 15 years.

Scientists are as of yet unclear as to how aspirin may help ward off cancer. However, it has been proposed that the medicine may inhibit specific enzyme functions that spur tumor growth.

Though researchers stop short of recommending the daily use of aspirin for everyone, they do suggest it may be helpful for some individuals. Through the research, it was found that taking aspirin doses above 75 mpg daily does not result in added health benefits. However, it was determined that individuals in their 40s and 50s responded most effectively to the effects of daily aspirin consumption.

Though the potential benefits of a daily aspirin may spur some to begin a daily regimen, it should be noted that the risk of internal bleeding increases with frequent aspirin consumption.


Researchers Identify Gene That Guards Cancer From Chemo

A cancer gene known as astrocyte elevated gene-1 (AEG-1) has been identified as a major contributor to chemotherapy resistance, according to researchers at Virginia Commonwealth University. The findings suggest that future treatment methods focused on switching off the expression of this gene may improve treatment success of chemotherapy regimens.

Cancer researchers have long viewed AEG-1 as an important gene in the study of cancer. Previous studies have already shown that the gene facilitates cancer cell survival by regulating a variety of critical intracellular processes. Now, the VCU team reports that AEG-1 is also responsible for regulating a tumor’s level of protective autophagy – a process that bolsters the cancer’s defenses against drugs and environmental attack.

According to Paul B. Fisher, Ph.D., of VCU Massey Cancer Center, “Understanding how AEG-1 promotes resistance to chemotherapy and enhances cancer cell survival may lead to treatments that inhibit this gene and its regulated pathways, thereby uncovering potentially new therapeutic targets that can be exploited to enhance the ability of anticancer drugs to fight tumors.”

The findings, which were published in the November 22nd online early edition of the Proceedings of the National Academy of Sciences (PNAS), may one day improve the survival rates of patients for a variety of aggressive cancer types.


Skin Rash From Erbitux Linked to Improved Lung Cancer Survival

Lung cancer patients who developed a rash following treatment with cetuximab (Erbitux) lived longer than those who displayed no such side effects, according to researchers at Hospital Grosshandsdorf in Germany.

While drug side effects are generally seen as a negative outcome of treatment, it would appear that individuals taking Erbitux might come to view skin rash as a positive sign.

For the study, the German researchers looked at hundreds of patients who had been diagnosed with non-small-cell lung cancer. Of the 518 patients reviewed who had taken Erbitux, it was noted that approximately 70 percent eventually reported an acne-like rash on the skin. This rash typically showed up within the first three weeks of treatment.

Surprisingly, the researchers noted that this sector of patients went on to live much longer than the non-rash sector. On average, those who reported a rash survived for 15 months, while those without a rash survived an average of 8.8 months.

Additionally, patients with the rash displayed an increased stoppage of cancer progression (5.4 months compared to 4.3 months).

While it is currently unclear why a skin rash may be an indicator to success rate for Erbitux, the findings could help doctors assess the effectiveness of lung cancer treatments in the future. Presumably, the manifestation of skin rash would indicate that Erbitux is delivering a positive effect on an individual’s cancer. As such, absence of the rash may help identify patients who need to be switched to an alternative treatment method.

Before such avenues can be recommended, the German team stresses that additional studies must be conducted to validate these initial findings. According to Dr. Francesco Perrone of the Istituto Nazionale Tumori in Naples, Italy, “The only way to verify the hypothesis that skin rash predicts the benefit of cetuximab is a randomized trial that compares interruption versus continuation of cetuximab in patients with skin rash after three weeks of treatment with cetuximab and chemotherapy.”

Erbitux is currently approved for treatment of squamous cell carcinoma, colorectal cancer and head and neck cancer. The drug is currently in Phase III clinical trials for the treatment of non-small cell lung cancer.


Improving Treatment by Targeting Cancer Stem Cells

Studies completed in 2008 suggested for the first time that cancer tumors might contain cancer stem cells. Stem cells are basic cell structures that have the ability to grow into a diverse variety of cell types. As such, cancer stem cells are the initial cancer cells that grow and divide to proliferate the illness.

Today, a wide variety of cancer drugs and treatments are effective at killing a high number of cancer cells. However, the ability of cancer stem cells to survive these treatments and start the growth process all over again often prevents them from offering long-term health benefits.

With the discovery of cancer stem cells, interest has quickly grown in favor of the idea for developing drugs that specifically target these unique cell structures.

Robert A. Weinberg of MIT and the Whitehead Institute for Biomedical Research is one of the emerging experts on the subject (it was his 2008 research that led to the discovery of tumor cells that may indeed harbor stem cells). Weinberg has worked closely with Piyush Gupta, a researcher that has done extensive research into how current drug treatments affect cancer stem cells.

As it turns out, there are currently very few conventional cancer drugs that measurably affect the health and function of cancer stem cells. With this fact in mind, Gupta set to work screening 16,000 unique compounds in the hopes of finding specific drugs that might effectively target stem cells.

Through Gupta’s research, it was found that an antibacterial known as Salinomycin proved to attack a large proportion of breast cancer stem cells. Now, a startup known as Verastem intends to research how Salinomycin may be used to create the first cancer treatment that specifically targets cancer stem cells.

Verastem also plans to screen an additional 300,000 compounds in an effort to find additional options that may target cancer stem cells.

Another startup that is focusing on cancer stem cell research is OncoMed. Based in Redwood City, CA, OncoMed researchers are looking to find ways to reduce the ability of cancer stem cells to self-renew. OncoMed currently has entered stage 1 clinical trials with its inaugural drug (OMP-21M18).


NASA Grow Light Relieves Chemotherapy Side Effects

A light used to grow plants on the Space Shuttle and in other NASA experiments may now be useful for earth-bound cancer patients.  Treatments with a light system called a High Emissivity Aluminiferous Luminescent Substrate (HEALS) have been shown to be effective in helping cancer patients deal with a painful and difficult side effect of chemotherapy treatment known as oral mucositis.

Signs of oral mucositis are sores and ulcers inside the mouth.  Oral mucositis is often painful and can hinder a patient’s ability to eat, drink and speak.  The open sores that occur with oral mucositis can also become infected, which leads the patient to experience more pain and possible fever.  The condition often arises in patients undergoing high dosages of chemotherapy, especially in those patients under treatment for bone marrow and stem cell transplants.

The treatment with the HEALS device involved moving the glowing red light along a patient’s face for up to ninety seconds on each side, every day for up to two weeks.  The small light emitting diodes (LEDs) each give off twelve times more light than the sun, and the device contains nearly three hundred diodes, so the light is powerful enough to penetrate the patient’s skin.  Since the light from the diodes produces very little heat, doctors and patients need not worry about burns due to exposure.  The device is also small and lightweight, about the size of a paperback book.

Dr. Donna Salzman worked as the main clinical physician during the HEALS trials, which were conducted at the University of Alabama at Birmingham Hospital.  She said that the effectiveness of the HEALS device was “phenomenal” and that patients showed “no adverse effects” from the treatment.  Overall, the trial data showed a 96 percent chance that the patients’ improvement could be attributed to treatment with the HEALS lights.

Robin Schumacher is a spokesperson for Quantum Devices, the manufacturers of the HEALS device.  Ms. Schumacher explained that the device works by sending light directly into the cells affected by oral mucositis, which increases the production of adenosine triphosphate (ATP), a chemical responsible for cellular metabolism and waste management.  She said that the device allows the cells to start the healing process and “increases (their) ability to take out the garbage”.

In its original incarnation, the HEALS devices, then known as the WARP 75, was used in the development of plant growth experiments on various NASA Space Shuttle missions.  The device emits light in the near infrared/far red end of the visible light spectrum, which was found to be useful in growing plants in an environment with little space and little to no sunlight.

The technology was also found to be useful in healing troublesome wounds, such as severe burns and skin ulcers related to diabetes. The device is currently awaiting premarket approval from the US Food and Drug Administration.

Helen Stinson, a NASA staffer who oversees the agency’s involvement in the HEALS project, said that the potential applications for the device are “exciting”.  She also said that the agency is “proud to be a part of the HEALS technology medical advancements”.



New Gene Set Discovery Improves Targeted Treatment for Lung Cancer

A specific genetic signature has been linked to a high risk for recurrence of non-small cell lung caner following surgery, according to a team of researchers led by pathologist Dr. Ming Tsao. The discovery provides an avenue for identifying high-risk patients who may benefit from chemotherapy treatments once surgical removal of the tumor has occurred.

Previous studies have shown that post-surgical chemotherapy does not necessarily improve a lung cancer patient’s survival rate. Thanks to the newly identified biomarker, Tsao and his colleagues believe doctors can now identify which patients are most likely to benefit from additional chemotherapy, while sparing low-risk candidates from “the potentially debilitating side effects of this treatment.”

The study builds on a previous research study (dubbed JBR.10) conducted by the National Cancer Institute of Canada (NCIC) that concluded non-small cell lung cancer patients enjoyed improved survival outcomes with the help of chemotherapy drugs such as vinorelbine and cisplatin following surgery.

To come to their conclusions, Tsao and team reviewed the genetic data of 133 patients who took part in the 2005 JBR.10 research study. Through this analysis, the team was able to identify 15 genes that correlated to a high recurrence of cancer in cases where chemotherapy was not administered following surgery.

A randomized review of the JBR.10 results also allowed researchers to effectively “predict” which patients eventually experienced the most benefit from chemotherapy following surgery. The research indicates that both stage-I and stage-II lung cancer patients may benefit from chemotherapy following surgery.

The study was funded in part by the NCIC and U.S. National Cancer Institute. Research was performed in conjunction with researchers from the Princess Margaret Hospital Cancer Program and Ontario Cancer Institute.



Blocking “Rogue Gene” May Prevent Cancer Spreading

Scientists at the University of East Anglia in England have reportedly discovered a “rogue gene” that can lead to the spread of cancer throughout the body.  The gene, labeled WWP2, attacks proteins in healthy cells that typically prevent the spread of cancer from one area of the body to another.  The researchers found that the WWP2 gene is often present in late-stage cancer patients as the disease moves to different organs, a process known as metastasis.

Metastasis often occurs in the late stages of the disease.  Cancer cells often spread through either the bloodstream or the lymph system and attack other organs.  In many cases, the metastasized tumors are the ones attributable for many fatalities, rather than the tumors at the original site.  The ability to prevent or forestall the metastatic process has long been considered an important factor in treating many forms of cancer.

Many types of cancer, including breast and colon cancers, are often aggressive and spread quickly throughout the body.  The research team also determined that the development of chemotherapy drugs that can target the WWP2 gene might interrupt the metastasis process.  The healthy cells, protected from the effects of WWP2, could fight off the cancerous mutations and prevent the spread of most types of cancers to other organs.

Dr. Andrew Chantry, one of the researchers who conducted the study, said that the work involved in creating such a drug “is a difficult but not impossible task”.  He also said that the biggest challenge would be to develop a drug that will attack the WWP2 gene within the cancer cells and stimulate the production of anti-cancer proteins.

Dr. Surinder Soond, another researcher on the study, said that the results showed “a novel and exciting approach” in the treatment of highly aggressive forms of cancer.  He also told reporters that the process “holds great potential” for preventing the spread of the disease.

Dr. Kat Arney, an official with the British agency Cancer Research UK, said that the WWP2 discovery “adds one more to this ever-growing list” of genes understood in the spread of cancer.  She said that the East Anglia study was helpful in learning more about the process behind how cancer spreads throughout the body, but that any potential applications of the discovery are ‘still at the laboratory stage”.

The discovery of the WWP2 gene has led to speculation that a new class of chemotherapy drugs could come about within the next ten years.  The anti-WWP2 drugs could prevent the spread of cancer to more susceptible organs, such as the heart or brain, while traditional chemotherapy routines or surgical procedures would still be used to attack the primary cancer site.


Scientists Fight Cancer With Cancer

Scientists at the Rogosin Institute in New York have found a new weapon in the fight against cancer: beads made from mouse cancer cells.  Researchers created the beads by removing cancer cells from mice and coating them in agarose, a sugar derived from seaweed.  In previous tests on animals, the study found that the beads significantly reduced the size of the surrounding tumors.

The beads start as a mixture of agarose and kidney cancer cells from mice.  The next step is to cover the mixture in another layer of agarose, creating the coating for the bead.  After three to ten days, almost all of the kidney cancer cells die off.  The remaining cells resemble cancer “stem cells” and begin to reproduce inside the bead.

As the stem cells divide and refill the bead’s interior, they emit proteins that other nearby cancer cells use as a signal.  The process essentially “tricks” cancer cells into believing that more cancer cells are nearby and that the existing cancer cells must stop growing.  In most cases, the tumors can stagnate, shrink, or die off entirely.

The process of testing the method on humans has already begun.  At least thirty cancer patients have been implanted with the beads, with more test subjects expected to join the study pending the early results.  The patients in the study have some of the most aggressive forms of cancer, including colon, pancreatic and prostate cancers, in the advanced stages of the disease.  The research team hopes to release the results from the small-scale study by the end of the year.

Dr. Howard Parnes, a researcher with the National Cancer Institute, called the efforts at Rogosin “a completely novel way” of looking at cancer treatment methods.  He said that the methods of moving mouse cancer cells into humans has yet to show any evidence of creating any ill effects on patients.  Dr. Parnes mentioned that the study showed a “remarkable proof of principle” that the genetic structure of cancer cells in one animal could be used as an effective treatment in another species.

Dr. Daniel Petrylak, director of the prostate-cancer program at Columbia University Medical Center, said that the results from the Rogosin study appear to be “very compelling”.  Dr. Petrylak said that he would soon select patients to take part in the next phase of the study.  Prostate cancer is often very aggressive and spreads quickly throughout the body, thus prostate cancer patients would be suitable candidates for further testing.

Dr. Barry Smith, director of the Rogosin Institute, said that the team’s results with lab mice were promising.  The study showed that mice treated with the beads showed a reduction in tumor size of up to sixty percent within a month of the procedure.  The group also treated eleven dogs with prostate cancer using the beads.  The dogs that received the beads lived an average of nearly six months, with one dog surviving for almost two years, compared with a typical survival time of less than two months for untreated dogs.


Blue Light Special: Killing Cancer With “Light Activation”

A new platinum-based compound that is activated by blue light offers a cancer-killing potency that is up to 80 times higher than that of current platinum-based anti-cancer drugs, according to research led by the University of Warwick.

Working in conjunction with researchers at Ninewells Hospital Dundee and the University of Edinburgh, the Warwick team hopes the new compound will improve cancer treatment effectiveness for a wide variety of cancers. According to Professor Peter Sadler, University of Warwick Department of Chemistry:

“This compound could have a significant impact on the effectiveness of future cancer treatments. Light activation provides this compound’s massive toxic power and also allows treatment to be targeted much more accurately against cancer cells.”

This assertion is backed up by initial tests performed at Ninewells Hospital Dundee. Here, a team tested the effectiveness of the new compound on killing cultivated esophageal cancer cells. The results of these studies were encouraging, with 50 percent of all cancer cells killed by a small concentration of 8.4 micro moles per liter of the compound.

Additional research for the compound is set to begin on ovarian and liver cancer cells.

Previous platinum-based compounds have been engineered to react to ultraviolet light. However, the narrow wavelength of ultraviolet rays has limited its real-world potential. Since the new compound reacts directly with visible blue light (as well as green light), it is expected to deliver a broader range of applications.

Researchers also report that the new compound is stable and easily administered. Additionally, it is water soluble, meaning that it simply dissolves and flushes from the body following treatment.

Peter Sadler explains that “light activation generates a powerful cytotoxic compound that has proven to be significantly more effective than treatments such as cisplatin.” As a result, the team has hopes that the new compound will offer effective treatment options for cancer types that do not traditionally respond well to platinum-based chemotherapy.