Friday, January 30, 2015

A new trial down the “Hedgehog” pathway for men with high-risk prostate cancer


Nearly ten years ago, Johns Hopkins researchers David Berman and Philip Beachy discovered the hedgehog pathway in mice with prostate cancer.[1] This molecular pathway is turned on in the embryologic development of lung, pancreas, prostate, brain and other organs during normal development. In prostate cancer, this pathway is abnormally turned "on" as prostate cancer grows and spreads. Patrick C. Walsh, MD, describes the pathway, "It's like soil and seeds. The soil is the stroma of the prostate — the connective tissue that serves as its framework — and the cancer cells are the seeds." And the Hedgehog protein is compost, sunlight and water — everything the seeds need to grow. "If these cells spread but try to grow in poor soil, they can't survive. But if they can manufacture the Hedgehog signal, they can make the soil that they need — they can pack their lunch and take it with them."

In their original study, published in Nature,[1] Drs. Berman and Beachy demonstrated that giving drugs that could block the Hedgehog pathway, could shrink human prostate cancer tumors in animals. That model is now ready for prime-time testing in humans. Dr. Ashley Ross, MD, PhD, Assistant Professor in Urology, Oncology, and Pathology, is partnering with Emmanuel Antonarakis, MD, medical oncologist, are opening a randomized, placebo-controlled clinical trial of a highly selective Hedgehog pathway inhibitor, called LDE225 and made by Novartis. Dr. Ross explains the hypothesis of the trial:

Ashley E. Ross, MD, PhD
"By looking at gene expression patterns, we and others have found that the Hedgehog pathway appears up-regulated in men with disease that metastasizes after local therapy. Also, in men with advanced prostate cancer, Itraconazole, which inhibits the Hedgehog pathway, appears to slow the disease by a mechanism independent of the androgen receptor. Itraconazole is an antifungal drug. Recently, new, Hedgehog pathway specific drugs with much more favorable toxicity profiles are available."

Men with high-risk prostate cancer are badly in need of a drug that could potentially prevent cancer growth and metastasis. In these patients, there is always the possibility that, even after surgery or radiation therapy, some cancer cells have already escaped the prostate, are hiding somewhere in the body, and will repopulate. Use of a systemic Hedgehog inhibitor may help wipe out these "micrometastatic" cells. Dr. Ross explains,
"We need to start thinking of high-risk disease as a different type of cancer, a systemic disease, and we have to start treating them like we treat other cancers, with a systemic approach in addition to surgery and/or radiation."

The trial is open to radical prostatectomy patients at Johns Hopkins with high-risk prostate cancer: men with a Gleason score of 8 to 10, a PSA of 20 or greater, or clinical stage T3 disease. The men who receive the drug will take the pill for four weeks before radical prostatectomy. All of the men will undergo a repeat biopsy and will have a molecular profile done on their cancer cells before surgery, and then will have the radical prostatectomy specimens examined afterward. Dr. Ross explains, "It's a pharmacodynamic trial, to see if this new drug actually gets into the prostate and inhibits the Hedgehog pathway as we expect it should. Of course, men will be followed closely following prostatectomy and we will also monitor whether superior cancer control results are achieved in those who received LDE225."


 


 

This blog and quotations are extracted from:
Target: Hedgehog Pathway, New Trial Opens for Men with High-Risk Prostate Cancer in Discovery, Volume XI, Winter 2015.

Hedgehog Blockers:Can They Stop Advanced Prostate Cancer? Scientists One Step Closer To Finding Out in Prostate Cancer Discovery, Volume II, Autumn 2005.

 

[1] Karhadkar SS, Bova GS, Abdallah N, Dhara S, Gardner D, Maitra A, Isaacs JT, Berman DM, Beachy PA. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature. 2004 Oct 7;431(7009):707-12. Epub 2004 Sep 12.

 

7 comments:

  1. It's amazing to see how fast this kind of technology is progressing. I didn't even know what a urologist was until my roommate had kidney stones. It turns out the kidney stones were a symptom of much larger problems. It was a good thing he checked out the causes more thoroughly. | http://drmatthewbui.com

    ReplyDelete
  2. Read the information you share, it is very helpful for me. Hope I will learn more interesting information on your blog.
    Chuyenhangvevietnam.com là một trong những đơn vị vận tải hàng hóa uy tín tại TPHCM. Chúng tôi cung cấp tới quý khách hàng các dịch vụ như: cho thuê xe tải 500kg tự lái, vận chuyển hàng hóa bằng container, vận chuyển ô tô bắc nam giá rẻ, công ty chuyển phát nhanh tại tphcm, giao hàng nhanh, giao hàng tận nơi, cho thuê kho, ship cod,... uy tín, chất lượng và giá cả cạnh tranh nhất thị trường hiện nay. Uy tín của công ty chúng tôi được xây dựng nên từ sự tin tưởng và hài lòng của tất cả các khách hàng đã sử dụng qua dịch vụ của chúng tôi.

    Nếu quý khách hàng đang tìm kiếm một đơn vị vận tải chất lượng, hãy liên hệ ngay với chuyenhangvevietnam của chúng tôi qua số hotline 1900 1247 để được tư vẫn kĩ hơn về các dịch vụ của chúng tôi.

    ReplyDelete
  3. Get rid of Cold Sores, unexpected Outbreak and HSV, HSV1, HSV2 and all kinds of Viruses infections with antiviral roots and herbs herbal medicine which is purely Natural, no side effects? don't have to keep waiting for treatment when the is a herbal medicine that Eradicate this Viruses. I was searching online for Herbal Cure for Herpes Virus when I saw a testimony online about Dr. Akintunde and how he cured a lady of HSV1 with his.
    natural herbal medicine and tested Negative and in less than a month she was cured of this virus. So it took me time to believe that this was true, because my family Doctor tried all his best to get rid of this virus in my body system but yet no cure and I suffered from outbreak and Cold Sores always. I had to contact Dr. Akintunde after I have access his website and i had faith in God that I was going to be fine and free of this virus one day. Finally I contacted Dr. Akintunde on his WhatsApp number that I saw on the testimony post online, and after our conversation the Doctor only promise me that I was going to be cured and free of this virus after taking his natural herbal medicine because I was tired of my situation with this virus it was so distracting to my life and whole family. Later Dr. Akintunde send some Herbal medicine to me through UPS courier service, with instructions on how to used this medicine, to my biggest surprise first week of taking my herbal medication I saw great improvement and I still think that it's a dream but this is real, I now test Negative of this virus today and my blood pressure well regulated now, my family doctor after my test was extremely surprise to see my test result change to HSV1 Negative and no more symptoms, cold sores, sores throat and outbreak again. I wish to tell everyone about this, mostly if you have this virus then do yourself good to contact Dr. Akintunde and see what the Lord can do through this Herbal Doctor's medicine in less than a month. 100% free from herpes Virus. I and my family say "thank you" Sir, for helping my life. You are a blessing to this generation and God will reward you richly

    Email: drakintundehomecare@gmail.com

    WhatsApp number: +234 703 524 5593

    ReplyDelete
  4. WHAT A GREAT MIRACLE THAT I HAVE EVER SEE IN MY LIFE. My names are Clara David I’m a citizen of USA, My younger sister was sicking of
    breast cancer and her name is Sandra David I and my family have taking her
    to all kind of hospital in USA still yet no good result. I decided to go to
    the internet and search for cancer cure so that was how I find a lady
    called peter Lizzy she was testifies to the world about the goodness of a
    herbal man who has the roots and herbs to cure all kind of disease and the
    herbal man email was there. So I decided to contact the herbal man @herbalist_sakura for my younger sister help to cure her breast cancer. I contacted him and told him
    my problem he told me that I should not worry that my sister cancer will be
    cure, he told me that there is a medicine that he is going to give me that
    I will cook it and give it to my sister to drink for one week, so I ask how
    can I receive the cure that I am in USA, he told me
    That I will pay for the delivery service. The courier service can
    transport it to me so he told me the amount I will pay, so my dad paid for
    the delivery fee. two days later I receive the cure from the courier
    service so I used it as the herbal man instructed me to, before the week
    complete my sister cancer was healed and it was like a dream to me not
    knowing that it was physical I and my family were very happy about the
    miracle of Doctor so my dad wanted to pay him 5 million us dollars the
    herbal man did not accept the offer from my dad, but I don't know why he
    didn't accept the offer, he only say that I should tell the world about him
    and his miracle he perform so am now here to tell the world about him if
    you or your relative is having any kind of disease that you can't get from
    the hospital please contact dr.sakuraspellalter@gmail.com or whats app him
    +2348110114739  you can follow him up on Instagram @herbalist_sakura for the cure, he will help you out with the
    problem. And if you need more information about the doctor you can mail me
    davidclara223@gmail.com 

    ReplyDelete
  5. All these post about HERBAL MEDICINE and spell casters are scammers and fake trying to collect money all in the name of HERPES cure and when you contact them, they will be asking for your name, pictures, country, phone number, occupation and when you have given them all the information, they will be asking for money. I was once suffering from GENETIC HERPES and i spent a lot of money going from one herbal doctor to another but they all scam and take my money away until i came in contact with this powerful one called Dr. Aire who cured me from Herpes with his herbal medication , after doctor Aire has finished preparing the herbal medicine, he asked me to send him my residential address, so that he will send the herbal medicine to via D.H.L so i did. 2days later, i received the herbal medicine and i had to follow the instructions he gave to me on how i will apply it. 2weeks later i went to hospital for test and according to the test done by the Medical doctor philip it stated that i was cured.
    So viewers be wise and beware of fake spell casters and fake herbal doctors, they are all over the internet trying to steal from poor people. I will drop you the email of this powerful herbal doctor just in case you wish to contact him for help. drairehome@gmail.com OR whatAspp him on +2347036740271 or call +2347036740271
    Dr Aire CAN AS WELL CURE THE FOLLOWING DISEASE:-

    1. HERPES
    2. LASSA FEVER
    3. GONORRHEA
    4. HIV/AIDS
    5. LOW SPERM COUNT
    6. MENOPAUSE DISEASE
    7. EPILEPSY
    8. ASEPSIS
    9. CANCER
    10. ANXIETY DEPRESSION  

    ReplyDelete
  6. I'm very excited to inform everyone that I'm completely cured from my HSV 1&2 recently. I have used Oregano oil, Coconut oil, Acyclovir, Val acyclovir, Famciclovir , and some other products and it's really help during my outbreaks but I totally got cured from my HSV 2 with a strong and active herbal medicine ordered from a powerful herbalist and it completely fought the virus from my nervous system and I was tested negative after three weeks of usage. I'm here to let y'all know that HSV 1& 2 has a complete cure, I got rid of mine with the help of Dr Moses Buba and his herbal exploit, AFTER I engage with other wrong doctors. Contact him via email: buba.herbalmiraclemedicine@gmail.com or Call/WhatsApp him at +2349060529305
    thank you..

    ReplyDelete
  7. I was diagnosed as HEPATITIS B carrier in 2013 with fibrosis of the
    liver already present. I started on antiviral medications which
    reduced the viral load initially. After a couple of years the virus
    became resistant. I started on HEPATITIS B Herbal treatment from
    ULTIMATE LIFE CLINIC (www.ultimatelifeclinic.com) in March, 2020. Their
    treatment totally reversed the virus. I did another blood test after
    the 6 months long treatment and tested negative to the virus. Amazing
    treatment! This treatment is a breakthrough for all HBV carriers.

    ReplyDelete