Category Archives: EphB4

New Drug Targets Cancer Caused By Asbestos

May 26, 2014

Mesothelioma lung cancer can come to those persons who loved, and simply hugged their parent who worked around asbestos.  For example, now at age 45, Heather Von St. James recalls her father working as a building demolition employee around materials containing asbestos.  He would return home each day thoroughly covered by dirt and dust. She remembers how much she enjoyed hugging her father each night.mesothelioma-studies

By age 36, Heather was diagnosed with mesothelioma, the deadly yet to be cured cancer connected with exposure to asbestos particles.  Mesothelioma can take decades to develop and it often kills within months after symptoms appear. Heather was a new mother to a 3-month-old daughter, and she was told her only chance to live was by having a lung removed.

In 2013, more than 107,000 people died worldwide from mesothelioma.  However, Heather opted for the surgery instead, and removed the disease in time to stay alive.   According to Ms. St. James, “There’s a lot of people who don’t.”

Fortunately for other people with mesothelioma, or those that will discover they have the deadly disease, a new wave of drugs developed and being tested are giving new hope that mesothelioma cancer may be slowed or stopped.  Drug researchers, like Verastem Inc. (VSTM), GlaxoSmithKline Plc (GSK), and Dr. Parkash Gill of the USC Norris Comprehensive Cancer Center have announced that they are testing new cancer fighting drugs.

According to Dean Fennell, a lead researcher doing a trial study with a new drug by Verastem:

“[Mesothelioma] is not a curable cancer; it’s not a disease that can be wiped out completely by surgery as you see with lung cancer. Finding ways to stop that process or slow it down can have big implications for patient survival.”

Unlike lung cancers, Mesothelioma affects the cell tissues that cover the lungs.  It can also affect the tissues around the heart and abdominal organs.  Like all cancers, mesothelioma is treated by doctors with cutting the cancer tissue out, or irradiating it, but both methods sometimes have dangerous side effects.

New Drugs Offer New Hope to Replace Old Treatments

Verastem (based out of Cambridge, Massachusetts) has developed a drug (VS-6063) that is now in late-stage human testing. Consecutively, Glaxo (based out of London) has a compound that is being tried in combination with another product in an early-stage study. The drugs from these two companies each target an enzyme involved in cell movement that permits the cancer to spread.

The enzyme is a key marker of aggressive cancers and is overabundant in many tumors that spread quickly. Also, patients with an inactive gene called Neurofibromatosis 2 (NF2) respond well to the test drugs being developed where nearly half of mesothelioma patients have inactive NF2s.

In the U.S. and Europe, the VS-6063 treatment has been granted orphan drug status.  This means that Verastem with their VS-6063 product is given seven (7) years of exclusive marketing.  A Bloomberg report states that according to four (4) analysts, the VS-6063 drug could possibly generate $450 million in sales by 2019 if the product is cleared for public use.

Earliest Stage

Defactinib is the medicine that targets early stage cancer stem cells.  These are considered to be theorigin of the cancer and frequently are resistant to existing therapies.   The cancer stem cells for mesothelioma are known to be particularly resistant to chemotherapy.

Now, Mr. Dean Fennell does not have an economic connection with Verastem, nor is he a paid consultant to the company.  And yet, Mr. Fennell (who is chairman of thoracic medical oncology at the University of Leicester in England) stated during an interview:

“The hope is we can suppress the cancer in such a way that it becomes a more chronic disease, rather than have a disease that’s going to progress relentlessly and kill the patient”

Verastem with a market value of about $215 million is developing the drug assisted by several renowned pharmaceutical companies providing guidance. The development team includes former Genzyme Corp. CEO Henri Termeer; Human Genome Project leader Eric Lander; and Phillip Sharp, a Nobel laureate at Biogen Idec Inc.

Other Drug Combinations

Under a license from Pfizer Inc., AstraZeneca Plc of London is testing a drug called tremelimumab, on mesothelioma in a mid-stage trial. The treatment works differently from the other developmental drugs in that it helps the patient’s immune system to recognize and kill cancer cells.  According to

Carolyn Buser-Doepner (VP for tumor signaling at Glaxo, the U.K.’s biggest drugmaker), there are plans to combine a new drug GSK2256098 with some other medicines to potentially make cancer treatments more effective.  In one early-stage trial, it will be paired up with Glaxo’s Mekinist, which is approved for melanoma.  She said, “The pre-clinical data are very encouraging. We’re very excited about it.”

Boehringer’s Drug

A fourth drug, nintedanib from Germany’s Boehringer Ingelheim GmbH, is in early-stage testing for mesothelioma, according to a spokesman. Unlike the previous mentioned medicines, this one works by targeting proteins directly related to the formation of blood vessels that feed tumors.

According to the director of research at the British Lung Foundation, Noel Snell, the kind of research studies most likely to yield improvements in cancer care are those that investigate the nature of the disease itself.  Still, treatments being tested today on mesothelioma are most encouraging.

Snell said in a statement:

“It is shameful that this kind of fundamental research remains so drastically underfunded, and that the number of trials available for mesothelioma patients is still dwarfed so dramatically by the number available to other cancer patients.”

Dr. Gill and EphB4 Treatment

For several years, Dr. Parkash Gill of the USC Norris Comprehensive Cancer Center has proceeded with Phase I Clinical Trials with the new cancer fighting drug Eph-B4 made available to qualifying mesothelioma patients. With generous support from the Mesothelioma Research
Foundation of America
, the initial Phase I Trial Eph-B4 has been available to newly diagnosed patients who have not Ask Dr. Gill about the most recent clinical trials avaialbleundergone any conventional lung cancer treatment options, as well as those patients who have exhausted all other treatment options such as surgery and chemotherapy.

The results of these recent clinical trials have truly been exciting as Dr. Gill reports that Eph-B4 is showing great promise as a solo treatment, or in conjunction with other drugs like Alimta, Cisplatin and Carboplatin.

The research of Dr. Gill, in conjunction with similar studies by other Oncologists, have improved the understanding among Primary Care physicians about the detection process, and given them better options to offer patients with lung cancer including mesothelioma.

Eph-B4 as a Better Treatment

Treatments have also gotten better because we now understand two principles: a)molecular changes in lung cancer with very specific mutations; and b)medication (like Eph-B4) that is specific to addressing the treatment of only one cellular abnormality.

As Dr. Gill with the Mesothelioma Research Foundation of America continues the goal to make mesothelioma a disease of the past, our understanding of the human body immune system has also improved.    From this we have Eph-B4, an immune specific treatment that assists a patient with lung cancer to live longer with fewer side effects.

His studies have contributed to the evolution of mesothelioma cancer research over the last decade.  Collectively, researchers are producing a canonical story in which the range of research works has grown a consensus among recognized oncologists and Primary Care physicians of a “great” or “major” break through with the two principles mentioned above.  Basically, we can now identify subsets of cancer in a patient at the molecular level and bring a retardant treatment (immunity) to that cancer in those patients.  And this observation continues to this day to be repeated by many research projects.  More than ever before, researchers continue to identify specific cancer mutations and use similar drugs to shut down these cancers and improve patient survival.

Asbestos: The Miracle Fiber That Kills

Asbestos was named the “miracle fiber,” but has become the topic and issue of many lawsuits claiming losses as well as damages from illness caused by asbestos products.  It was commonly used in building materials such as insulation for years because it was cheap, abundant and heat-resistant.

Many countries have banned asbestos mining.  However, the World Health Organization estimates that as many as 125 million people worldwide continue to be exposed to asbestos either at work or in their homes because it continues to be mined and made into  products from in RussiaChina and India.

Unfortunately, mesothelioma cancer can lay dormant for as long as 50 years before spreading, which explains why rates have risen long after many countries have banned the asbestos.

New cases of mesothelioma cancer in the United Kingdom, where asbestos was restricted starting in the 1980s and outlawed fully in 2006, were 2,125 in 2012.  These numbers are expected to peak in 2015.  In the United States, the number of new cancer cases has been stable, hovering around 3,000 per year since 2000.  This stability was expected because of extensive efforts put into public education.  Still, a complete ban of Asbestos in the U.S. was overturned in the courts.  One of the world’s largest asbestos exporters, Canada, closed its remaining mines in 2011.

An Asian Asbestos Mesothelioma Cancer ‘Tsunami’

In Japan, asbestos was banned in 2006, the Japanese government pays the full cost of treatment for related illnesses, and rate of new cases of cancer are predicted to continue rising until 2027.  The director of a World Health Organization occupational health group, Ken Takahashi, has warned Asian governments to prepare themselves for an “asbestos tsunami.”

Again, Dean Fennell reminds us:

 “In the early ’70s, this was an incredibly rare disease. Now my clinic is full of patients with mesothelioma. Because the rates are increasing, we have a real need now to identify effective treatment.”

A cure for mesothelioma can not be found fast enough.  Still, there are survivors like Heather Von St. James, who breaths with great effort during Minnesota winters with her one remaining lung, and she volunteers her time to be a coach to other mesothelioma patients.   By her personal experience with mesothelioma, she wants other victims of mesothelioma to understand:

 “If they can keep it under control,
that’s the first hope.”

 

Eph-B4: An Improvement and Better Options for Lung Cancer Patients

PRESS RELEASE
February 23, 2014

Ask Dr. Gill about the most recent clinical trials avaialbleFor several years, Dr. Parkash Gill of the USCNorrisComprehensiveCancerCenter has proceeded with Phase I Clinical Trials with the new cancer fighting drug Eph-B4 made available to qualifying mesothelioma patients. With generous support from the Mesothelioma Research Foundation of America, the initial Phase I Trial Eph-B4 has been available to newly diagnosed patients who have not undergone any conventional lung cancer treatment options, as well as those patients who have exhausted all other treatment options such as surgery and chemotherapy.

The results of these recent clinical trials have truly been exciting as Dr. Gill reports that Eph-B4 is showing great promise as a solo treatment, or in conjunction with other drugs like Alimta, Cisplatin and Carboplatin.

The research of Dr. Gill, in conjunction with similar studies by other Oncologists, have improved the understanding among Primary Care physicians about the detection process, and given them better options to offer patients with lung cancer including mesothelioma.

Improvements for cancer patients

Early detection of lung cancer has improved with the use of Spiral CT scanners.  Computed tomography (CT) is an imaging procedure that uses special x-ray equipment to create a series of detailed pictures, or scans, of areas inside the body. It is also called computerized tomography and computerized axial tomography (CAT) scanning.   In cancer, CT may be used to help detect abnormal growths; to help diagnose tumors; to provide information about the extent, or stage, of disease; to help in guiding biopsy procedures or in planning treatment; to determine whether a cancer is responding to treatment; and to monitor for recurrence.  For people who do not have lung cancer but are at risk, the proper and early use of a CT scanner with annual inspections can reduce mortality rates in the US by 20%.

Eph-B4 as a Better Treatment

Treatments have also gotten better because we now understand two principles: a)molecular changes in lung cancer with very specific mutations; and b)medication (like Eph-B4) that is specific to addressing the treatment of only one cellular abnormality.

As Dr. Gill with the Mesothelioma Research Foundation of America continues the goal to make mesothelioma a disease of the past, our understanding of the human body immune system has also improved.    From this we have Eph-B4, an immune specific treatment that assists a patient with lung cancer to live longer with fewer side effects.

Our research has contributed to the evolution of mesothelioma cancer research over the last decade.  Collectively, researchers are producing a canonical story in which the range of research works has grown a consensus among recognized oncologists and Primary Care physicians of a “great” or “major” break through with the two principles mentioned above.  Basically, we can now identify subsets of cancer in a patient at the molecular level and bring a retardant treatment (immunity) to that cancer in those patients.  And this observation continues to this day to be repeated by many research projects.  More than ever before, researchers continue to identify specific cancer mutations and use similar drugs to shut down these cancers and improve patient survival.

The Future in Lung Cancer Research

The development of research in cancer resistance will be the next wave of understanding and will lead research teams into novel ways to overcome cancer resistance to treatments.  This will include discovery efforts through second and third generation cancer inhibitors; incorporation of other cancer targets that may be found; and possibly adding inhibitors that may change protein folding associated with molecular cancer mutation.  Each new discovery makes an opportunity to also create a specific, focused drug treatment.

Going forward with mesothelioma cancer research, our researchers will also begin defining those cancer mutations in which there is no antigen driver.  We will learn how to integrate targeted agents, how to sequence and / or combine them to inhibit multiple cancer growth signals.  Future research will also teach us how to do inhibitor agent integration so that the toxicity of the treatment is most effective and safe for the cancer patient.

Lung Cancer Early Detection Saves Lives

The cancer research industry and medical doctors practicing lung cancer treatment will become more proficient at explaining the benefits of the complex investigation associated with lung cancer screening tests.  Primary care physicians will become more knowledgeable and comfortable with their understanding of the new research about lung cancer.  Presentations about lung cancer screening and its benefits will help persons at risk of lung cancer to have less fear about the process and discover how screening saves lives; maybe their life.  While considering the costs and benefits of lung cancer screening, one must also balance the perspective with the knowledge of 160,000 persons who die each year from lung cancer, which many might be saved by choosing lung cancer screening.

Phase II Clinical Trials of Eph-B4 to Soon Begin

Dr. Gill has several mesothelioma cancer victims currently in the Phase I clinical trial using the Eph-B4 drug, and being treated at USCNorrisComprehensiveCancerCenter in Los Angeles.  The improved results these cancer patients are displaying are very encouraging to the USC Norris cancer research team.  Consequently, Dr. Gill has recently received permission from the FDA to enter into clinical trials for Phase II.  This study will proceed and include cancer patients with mesothelioma as well as pancreatic cancer.

Contact Dr. Gill for more information: (800) 909-6376 or www.mesorfa.org (ask Dr. Gill)

Reference:

  • Dr. Parkash S. Gill is a professor of Medicine and Pathology and leads the MesoRFA.org research team.
  • The Mesothelioma Research Foundation of America has a mission: fund research that will lead to the quickest cure for mesothelioma. Since 2001, the foundation has funded the Cancer Research Laboratory under the supervision of Dr. Gill at the USC/Norris Comprehensive Cancer Center in Los Angeles.  Dr. Gill (a board certified oncologist and hematologist) has received FDA approval to provide Clinical Trials for lung cancer patients using new treatment drugs with research 100% funded by the foundation.  We are all very excited at the possibilities of a more effective treatment over what presently is available for lung cancer victims.

Dr. Parkash Gill and Novel Therapeutic Targets (EphB4, Axk, GRP78) in Pancreatic Cancer

English: Gene expression pattern of the EPHB4 ...
Gene expression pattern of the EPHB4 gene

Ephrin type-B receptor 4 is a protein that in humans is encoded by the EPHB4 gene.[1][2]

Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. The Eph family of receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. The protein encoded by this gene binds to ephrin-B2 and plays an essential role in vascular development.[2][3]

APA/Hirshberg Symposium: Celebrating 10 Years of the Hirshberg Seed Grant THERAPY Novel Therapeutic Targets (EphB4, Axk, GRP78) in Pancreatic Cancer Dr. Parkash Gill.

  1. Bennett BD, Wang Z, Kuang WJ, Wang A, Groopman JE, Goeddel DV, Scadden DT (Jun 1994). “Cloning and characterization of HTK, a novel transmembrane tyrosine kinase of the EPH subfamily”. J Biol Chem 269 (19): 14211–8. PMID 8188704.
  2.  Jump up to:a b “Entrez Gene: EPHB4 EPH receptor B4”.
  3. Jump up Gerety SS, Wang HU, Chen ZF, Anderson DJ (1999). “Symmetrical mutant phenotypes of the receptor EphB4 and its specific transmembrane ligand ephrin-B2 in cardiovascular development.”. Mol. Cell 4 (3): 403–14. doi:10.1016/S1097-2765(00)80342-1PMID 10518221.