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).


World’s First Cancer-Killing Pill May be Available Within the Decade

Thanks to advancement made possible through the Human Genome Project, British researchers believe the world’s first cancer-killing pill may be on the horizon. According to the team’s timeline, such a pill may be available in as few as ten years.

The success of this future pill will work by exploiting a specific gene flaw that is present in cancer’s DNA. In lab tests, the British team was able to show that a mutation of specific cancer cells effectively blocked the disease’s ability to repair damaged genetic material. As such, a pill or injection could potentially be made that switches on this mutation and shuts down important repair mechanisms that cause the illness to grow uncontrollably.

Since such a drug would not affect the health of normal human cells, it is believed that treatment will not only be more effective, but also result in far fewer side effects.

A research team led by Professor Ghulam Mufti at Kings College London announced the findings on October 24th. Mufti summed up the findings by saying, “The genetics of cancers are being rapidly unraveled. We are soon going to have a library of what genetic abnormalities lead to which cancers. If these are specific, we can target these abnormalities using new treatments.”

Many researchers not affiliated with the study agree that all cancers are moving towards a targeted treatment process. Thanks in large part to the Human Genome Project, various research teams are now identifying potential genetic markers that may eventually lead to a cure for cancer.

One of the first of such drugs is currently being tested at the Breakthrough Breast Cancer Research Centre in London. This drug works in exactly the same manner as described by Mulfti – by altering a tumor’s cells so they cannot successfully repair DNA properly.

In early trials, the research team was able to show that breast cancer cells are killed while healthy cells are largely unaffected. The team also notes a complete lack of noticeable side effects.

Similar methods are also currently in the works for curing such illnesses as cystic fibrosis. Current medical trials that utilize gene therapy could lead to an effective cystic fibrosis treatment in as little as five years.


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.



Anemia Drugs May Decrease Survival Time Among Cancer Patients

Doctors need to exhibit extreme caution before prescribing a class of anemia drugs known as erythropoeisis-stimulating agents (ESAs) to cancer patients, according to an updated guideline endorsed by the American Society of Hematology (ASH) and American Society of Clinical Oncology (ASCO).

Anemia is a fairly common side effect of chemotherapy. As a result, ESAs such as Procrit, Epogen and Arenesp are frequently prescribed to stimulate the production of additional red blood cells. While such medications are typically preferred over the alternative of blood transfusions, experts warn that such drugs have been linked to reduced survival times of cancer patients. An increased risk of internal blood clotting has also been noted.

According to the new guidelines, physicians are urged not to recommend ESAs for any cancer patient who is currently not undergoing chemotherapy (with the exception of patients with myelodysplastic syndrome). For patients dealing with chemotherapy, new guidelines suggest physicians should discuss the many benefits and risks of ESAs directly with each patient. When discussing these risks, it is also important to discuss the alternative of blood transfusions and how this alternative may affect quality of life.

These updated recommendations are based on the analysis of a variety of information sources. These sources include analysis of published clinical trials, various medical literature and reviews of individual patient data.

Further recommendations for dosage levels, thresholds for initiation and modification of ESAs are also detailed in the new guidelines. According to ASH member Samuel Silver, MD, “These are issues that confront practicing hematologists and oncologists on a daily basis, and we hope that these evidence-based recommendations will influence practice standards and result in better care for patients.”

Complete data related to the revised guidelines can be found at the following website:

Complete guidelines will also be published in the November 18th issue of Blood and the November 20th issue of the Journal of Clinical Oncology.


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.


New Blood Test Could Improve Diagnosis and Treatment of Cancer

New blood test technology has been developed that is sensitive enough to detect cancer cells, according to researchers at Massachusetts General Hospital (MGH) and Veridex (a division of Johnson & Johnson).

A press release published by Johnson & Johnson suggests the technology, which is currently in development for commercial use, “will enable [circulating tumor cells] to be used both by oncologists as a diagnostic tool for personalizing patient care, as well as by researchers to accelerate and improve the process of drug discovery and development.”

A prototype of the technology has previously been able to successfully identify a variety of cancer cells in the blood (such as breast cancer, lung cancer and prostate cancer). The device is similar in size to a business card and makes use of a microfluidics chip to sift through blood samples and identify any signs of cancer.

Each microfluidics chip contains tens of thousands miniscule posts that are encased with a binding molecule. Different posts contain a different protein that is identified with different types of cancer. As such, if tumor cells are present in the blood sample, then they will stick to those posts that contain the matching binding protein. Based on this information, an identification of cancer can quickly be made.

Physicians and researchers are hopeful that the technology will not only ease diagnosis, but also assist in developing improved treatment regimens. This may be accomplished by routinely monitoring cancer cell counts to determine if a current treatment is offering positive effects. Additionally, the level of precision provided by the technology allows doctors to learn whether or not a specific tumor contains common genetic mutations that may warrant alternative treatment methods.

Though the current estimated cost of production is fairly expensive (each chip costs around $500), researchers are hopeful that the technology will one day be available on a global scale.

Ideally, the new blood tests will take a lot of the guesswork out of selecting a cancer therapy. According to Dr. Peter Ravdin, director of the Comprehensive Breast Health Center at the University of Texas Cancer Therapy & Research Center, current protocol requires doctors to “wait about three months and take an x-ray to see if the tumor has gotten smaller” once a treatment has been implemented.

With the help of Johnson & Johnson’s new technology, this wait-and-see timeline has the potential to be dramatically reduced.


Hormone Receptor Identified as Potential Target for Cancer Treatment

At least 11 common cancers may be partially spurred by the presence of the follicle stimulating hormone (FSH), according to research conducted at the Mount Sinai School of Medicine and France’s National Institute of Health and Medical Research.

The findings suggest that cancer treatments that target FSH within cancerous tumors may serve as a viable method for both detecting early signs of cancer and treating the illness.

FSH is a receptor that is normally present within the blood vessels of reproductive organs. In woman, it contributes to the growth of ovarian follicles and production of estrogen. In men, the hormone assists in the production of spermatozoa.

Among organs outside the reproductive system, FSH is typically absent. However, analysis conducted by the Mount Sinai team reveals that FSH also pops up in blood vessels of certain types of cancer. The 11 cancer types linked to FSH include:

• Breast cancer
• Prostate cancer
• Colon cancer
• Pancreatic cancer
• Bladder cancer
• Kidney cancer
• Lung cancer
• Liver cancer
• Stomach cancer
• Testicular cancer
• Ovarian cancer

Interestingly, the presence of FSH was identified across all 11 cancers regardless of stage of the tumor. This fact indicates that FSH serves as a biomarker that can be used to facilitate early diagnosis.

According to the study’s lead researcher, Aurelian Radu, “This new tumor marker may be used to improve cancer detection. Tumor imaging agents that bind to the new marker could be injected in the vasculature and would make visible early tumors located anywhere in the body,” said Aurelian Radu of Mount Sinai, the study’s lead author.

These findings are based on research that examined biopsies of more than 1,300 cancer patients.

Beyond early detection, Radu and colleagues are hopeful that FSH can also be used as a successful target for treatment. Since the receptor is linked to growth of tumor blood cells, treatments targeting FSH may assist in:

• Blocking the formation of new blood vessels
• Inhibiting blood flow to tumors via coagulation
• Destroying existing tumor blood vessels

In all three cases, the desired outcome is a reduction of oxygen flow to the cancerous tumor. Ultimately, this outcome could result in reduced growth, shrinkage or altogether elimination of a tumor.

One major advantage of using FSH as a target for cancer treatment is that it is absent in most normal tissues. This means that FSH-related drugs may result in fewer side effects than current chemotherapy treatments.

Before treatment avenues that relate to FSH production can begin, the research team concedes that additional research is needed. Additionally, the team reiterates the need to search for the role of FSH beyond the 11 cancers already studied.

The Mount Sinai research was published in the October 21 issue of the New England Journal of Medicine.