13 replies to this topic

[Hedgehog]

A little update of clinical data. Please note some of these patients have been on the drug for over 2 years now and had very poor prognoses. Also Genentech is trying to get first line treatment for colon cancer and if this looks good then a very very broad expansion of the program to a number of different cancers.

Please view the attachements (can be graphic)

http://cc.talkpoint....tity=86_8KD2JEN (presentation)

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[tunt01]

interesting thx.

[Hedgehog]

interesting thx.

There is also a natural inhibitor of this called cyclopamine and has been well characterized as specific Hedgehog Pathway (Hh) antagonist

http://en.wikipedia....iki/Cyclopamine

[tunt01]

interesting thx.

There is also a natural inhibitor of this called cyclopamine and has been well characterized as specific Hedgehog Pathway (Hh) antagonist

http://en.wikipedia....iki/Cyclopamine

isn't this treatment the kind of thing TheFirstImmortal needs? i thought he had small lung cell cancer and this molecule by genentech treats it?

[Hedgehog]

interesting thx.

There is also a natural inhibitor of this called cyclopamine and has been well characterized as specific Hedgehog Pathway (Hh) antagonist

http://en.wikipedia....iki/Cyclopamine

isn't this treatment the kind of thing TheFirstImmortal needs? i thought he had small lung cell cancer and this molecule by genentech treats it?

Yes I think I mention some time ago he should try to get on the clinical trial for "Compassionate Use" there is also a company called "Infinity" who is conduction a phase I trial of their Hh antagonist.

This would work very well for SCLC. Genentech even presented some Pre-Clinical data on SCLC and the Hh antagonist.

[tunt01]

interesting thx.

There is also a natural inhibitor of this called cyclopamine and has been well characterized as specific Hedgehog Pathway (Hh) antagonist

http://en.wikipedia....iki/Cyclopamine

isn't this treatment the kind of thing TheFirstImmortal needs? i thought he had small lung cell cancer and this molecule by genentech treats it?

Yes I think I mention some time ago he should try to get on the clinical trial for "Compassionate Use" there is also a company called "Infinity" who is conduction a phase I trial of their Hh antagonist.

This would work very well for SCLC. Genentech even presented some Pre-Clinical data on SCLC and the Hh antagonist.

Roche is in the process of trying to acquire Genentech. I would buy a share of Roche and apply for compassionate use directly at Genentech. If they deny you, threaten to sue on the basis of discrimination because you are a Roche shareholder.

[thefirstimmortal]

Hi Hedgehog,
I have an update for you. I short time ago I found out why I was having such a hard time getting the IHC data for you. They simply didn't do it. I'm in the process of switching doctors and have met with one who is willing to help me put together the program I want to have put together, including possibly using the kind of test that Kurt has refused to use. I could sure use you help on some of this. How strapped for time are you?

Edited by thefirstimmortal, 22 March 2009 - 04:57 AM.

[Prometheus]

Very impressive.

http://www.cancer.go...earchid=5955513

[Hedgehog]

Hi Hedgehog,
I have an update for you. I short time ago I found out why I was having such a hard time getting the ICH data for you. They simply didn't do it. I'm in the process of switching doctors and have met with one who is willing to help me put together the program I want to have put together, including possibly using the kind of test that Kurt has refused to use. I could sure use you help on some of this. How strapped for time are you?

Hi TFI,

Can you send me a link of what you are planning to-do or take?


Online book (go to page 294)
http://books.google....m...6&ct=result


SCLC & Hh

One additional area that deserves mention is the possible identification of the tumor stem cell population in SCLC. Several studies have suggested the presence of a subpopulation of cells (tumor stem cells) in solid tumors that are able to regenerate and propagate the tumor. Recently, Gutova and colleagues identified a rare population of cells in SCLC cell lines that were urokinase-type plasminogen activator receptor (uPAR)-positive and possessed clonigenic activity and marked resistance to chemotherapy when compared with the uPAR-negative population that was chemosensitive and did not posses clonigenic activity.[1] Further study is required to demonstrate whether this uPAR-positive group of cells may be the putative stem cell population for SCLC. Hedgehog Signaling Pathway

In addition, the hedgehog pathway (an embryonic signaling pathway) has been shown to be activated in airway epithelium in response to injury, and this is thought to lead to malignant change by repeatedly expanding the airway stem cell pool. The cells within SCLC tumors in vivo that are involved in hedgehog signaling are compartmentalized and appear to recapitulate the process seen in airway development and injury repair. It has therefore been speculated that these cells are maintained as tumor stem cells through ongoing hedgehog signaling.[2,3] Treatment of SCLC cell lines and xenografts with cyclopamine (a specific hedgehog pathway inhibitor) produces tumor growth arrest in both models.[4] Currently, GDC-0449, an orally bioavailable synthetic inhibitor of the hedgehog pathway is in phase I and II studies in patients with solid tumors, including SCLC.

http://www.cancernet...e/10165/1355177

Hh Infinity

today announced that preclinical data from a model of small
cell lung cancer (SCLC) show that following treatment with chemotherapy,
once-daily oral administration of IPI-926 leads to a statistically significant
delay in tumor re-growth, compared to vehicle control (p=0.01). These results
suggest that inhibiting the Hedgehog pathway with IPI-926, Infinity's novel,
potent Hedgehog pathway antagonist following chemotherapy delays tumor
recurrence in SCLC. These data were presented today during the Annual Meeting of
the American Association of Cancer Research (AACR) in San Diego, California.

"These data suggest a subpopulation of 'progenitor-like' cancer cells -- cells
that are chemo-resistant and Hedgehog responsive -- are being affected by
IPI-926," commented Vito Palombella, Ph.D., vice president of drug discovery at
Infinity. "We believe this approach is an exciting opportunity for clinical
development of IPI-926, as the data suggest that administration of IPI-926 could
lead to increased relapse-free survival for patients living with this aggressive
and difficult to treat cancer."
http://www.reuters.c...008 PNW20080415

[Hedgehog]

Roche is in the process of trying to acquire Genentech. I would buy a share of Roche and apply for compassionate use directly at Genentech. If they deny you, threaten to sue on the basis of discrimination because you are a Roche shareholder.

LOL I suppose so.

It appears that there is enough people willing to help TFI that we could get some body to purify some cyclopamine for him.... However, I would still try a clinical trial...

[thefirstimmortal]

Hi Hedgehog,
I have an update for you. I short time ago I found out why I was having such a hard time getting the ICH data for you. They simply didn't do it. I'm in the process of switching doctors and have met with one who is willing to help me put together the program I want to have put together, including possibly using the kind of test that Kurt has refused to use. I could sure use you help on some of this. How strapped for time are you?

Hi TFI,

Can you send me a link of what you are planning to-do or take?

Start with this post and read to bottom of thread. I'll fish out the other posts and post it in the fighting cancer thread.

http://www.imminst.o...&...st&p=301661

Edited by thefirstimmortal, 22 March 2009 - 04:58 AM.

[thefirstimmortal]

Start with this post and read to bottom of thread. I'll fish out the other posts and post it in the fighting cancer thread.

Here are the other posts.

http://www.imminst.o...&...st&p=302269

http://www.imminst.o...&...st&p=302376

http://www.imminst.o...&...st&p=302401

http://www.imminst.o...&...st&p=302671

http://www.imminst.o...&...st&p=303205

http://www.imminst.o...&...st&p=303332

[Hedgehog]

A little update of clinical data. Please note some of these patients have been on the drug for over 2 years now and had very poor prognoses. Also Genentech is trying to get first line treatment for colon cancer and if this looks good then a very very broad expansion of the program to a number of different cancers.

Please view the attachements (can be graphic)

http://cc.talkpoint....tity=86_8KD2JEN (presentation)

Update on number of clinical trials.

• Colon Cancer
• Ovarian Cancer
• Advanced Basal Cell Cancer
• Pancreatic Cancer *
• Brain Cancer (Medulloblastoma, Common brain cancer in children)*

*Please note that these clinical trials are sponsored by National Cancer Institute (NCI)

ALSO please note NCI is really (finally picking up on this pathway)

Novel Agents for Cancer Treatment. Initiate early phase clinical trials of novel agents in three areas: 1) targeting the tumor stem cell by evaluating the sonic hedgehog smoothened antagonist, GDC-0449, and the pan-notch inhibitor, RO4929097, in collaboration with Genentech and Roche, respectively, in trials of breast, lung, colon, leukemia and ovarian cancer; 2) testing Anti-IGFR-1 Monoclonal Antibody IMC-A12 (ImClone) in pediatric tumors such as rhabdomyosarcoma, osteosarcoma, and neuroblastoma, as well as studies in breast, small cell lung, adrenocortical and pancreatic cancer; and 3) testing PARP inhibitor ABT-888 in breast, ovarian, and pancreatic cancer. Contact: Dr. Jeff Abrams, 301-496-2522, abramsj@mail.nih.gov

http://grants.nih.go...rity_Topics.pdf

Also the NOTCH inhibitor fits nicely into the theory of ADULT STEM CELLS cause cancer...

[Hedgehog]

A little update of clinical data. Please note some of these patients have been on the drug for over 2 years now and had very poor prognoses. Also Genentech is trying to get first line treatment for colon cancer and if this looks good then a very very broad expansion of the program to a number of different cancers.

Please view the attachements (can be graphic)

http://cc.talkpoint....tity=86_8KD2JEN (presentation)

Update on number of clinical trials.

• Colon Cancer
• Ovarian Cancer
• Advanced Basal Cell Cancer
• Pancreatic Cancer *
• Brain Cancer (Medulloblastoma, Common brain cancer in children)*

*Please note that these clinical trials are sponsored by National Cancer Institute (NCI)

ALSO please note NCI is really (finally picking up on this pathway)

Novel Agents for Cancer Treatment. Initiate early phase clinical trials of novel agents in three areas: 1) targeting the tumor stem cell by evaluating the sonic hedgehog smoothened antagonist, GDC-0449, and the pan-notch inhibitor, RO4929097, in collaboration with Genentech and Roche, respectively, in trials of breast, lung, colon, leukemia and ovarian cancer; 2) testing Anti-IGFR-1 Monoclonal Antibody IMC-A12 (ImClone) in pediatric tumors such as rhabdomyosarcoma, osteosarcoma, and neuroblastoma, as well as studies in breast, small cell lung, adrenocortical and pancreatic cancer; and 3) testing PARP inhibitor ABT-888 in breast, ovarian, and pancreatic cancer. Contact: Dr. Jeff Abrams, 301-496-2522, abramsj@mail.nih.gov

http://grants.nih.go...rity_Topics.pdf

Also the NOTCH inhibitor fits nicely into the theory of ADULT STEM CELLS cause cancer...

Lets add another clinical trial SCLC for this Hedgehog Inhibitor



Purpose
RATIONALE: Drugs used in chemotherapy, such as cisplatin and etoposide phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. GDC-0449 may slow the growth of tumor cells. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving cisplatin and etoposide are more effective when given together with GDC-0449 or cixutumumab in treating small cell lung cancer.

PURPOSE: This randomized phase II trial is studying cisplatin and etoposide phosphate to see how well they work when given with or without GDC-0449 or cixutumumab in treating patients with extensive-stage small cell lung cancer.