I put this list here because it makes me feel better that so many good and dedicated people are working on ovarian cancer (cancer generally). If you know of any therapies not listed here, please contact me:

01. NIH TriCom Vaccine targeting Muc1
02. Telik's drug candidate Telcyta
03. Antisoma and Roche drug candidate Pemtumomab/AS1404
04. Introgen Therapeutics drug candidate INGN 241
05. Lpath Therapeutics drug candidate Sphingomab
06. Tibotec Therapeutics drug DOXIL
07. PharmaMar and Johnson and Johnson drug candidate YONDELIS (TM)
08. Schering-Plough drug candidate CAELYX (Peg-Doxil)
09. Genentech and Roche drug Avastin
10. Genentech drug candidate Pertuzumab
11. National Cancer Institute Study drug Gleevec
12. GPC Biotech drug candidate Satraplatin
13. Geron drug candidate GRN163L
14. Myriad Genetics drug candidate MPC-2130
15. CuraGen and Topo Target A/S drug candidate PXD101
16. Tulane University Ovarian Cancer Study drug Ontak
17. GlaxoSmithKline drug Topotecan
18. Eli Lilly drug Gemzar (gemcitabine)
19. Rexahn drug candidate RX-0201
20. Novogen drug candidate Phenoxodiol (PXD)
21. ViRexx drug candidate OvaRex(R) MAb
22. Celgene (Monsanto) Thalomid (Thalidomide); Revlimid
23. VioQuest Pharmaceuticals Inc. drug candidate Tricirbine
24. Amgen drug candidate MPC-2130
25. Cell Therapeutics drug candidate Xyotax
26. Oxigene drug candidate CA4P
27. ArQule: ARQ-501 drug candidate ß-Lapachone
28. HANA BIOSCIENCES, INC.drug candidate TALOTREXIN (PT-523)
29. Ångstrom Pharmaceuticals drug candidate A-6

The immune system rejects invading pathogens (bacteria and viruses) by recognizing components of these organisms as 'foreign'. Cancer cells also have components which are different from normal cells. These components can be isolated as genes (DNA), or as the corresponding protein, thus providing materials for use as antigens for immunization. Current studies focus on the MUC1 antigen which is over-expressed and differently processed by ovarian cancers.

Many cancers, including ovarian, over-express epithelial mucin (MUC1) and promote anti-MUC1 antibodies that may correlate with more favorable prognosis. By extension, risk for ovarian cancer might be reduced by pre-existing MUC1-specific immunity. A European Union project "Cancer Immunotherapy" aims at the development of an effective immunotherapy for breast cancer (and ovarian), based on dendritic cell (DC) vaccines using the tumor-associated cell surface glycoprotein MUC-1 as antigen. In a first phase of the project this includes the generation of dendritic cells, the production of the cancer related immunogen MUC-1, the development of new and the improvement of existing strategies for enhanced antigen presentation by DC's. The objectives of the Institute of Medical Virology as partner of the EU-network "Cancer Immunotherapy" are (i) To establish a strategy for delivery of MUC1-based immunogens by developing virus like particles or viral constructs coding for or packaging the antigen of interest. (ii) To evaluate the possibility for enhancing antigen uptake by coupling of MUC1 to transfer peptides. BACKGROUND: Aberrations in expression of mucin glycoproteins have been observed during malignant transformation of human ovarian epithelium. To date, several secretory mucin genes designated the MUC gene family have been identified, of which MUC1 encodes a mammary-type and MUC2 an intestinal-type epithelial mucin.

The NIH has a phase one study in the United States involving three ovarian cancer patients. A phase two study is underway in Australia.

Anne Helman: "Update on one woman at NIH on the TriCom Vaccine targeting Muc1 - after 3 months on the trial and completion of the core phase, her CA125 marker is NORMAL and the results of CT Scan from December 23, 2005 show her to be CANCER FREE. This is, of course wonderful news for her and for the ovarian community now awaiting results of scans for a second woman on this trial. While we know that not everyone responds to the vaccine [as evidenced by the trials that have been ongoing in other cancers], it is encouraging to see such a stunning response in an ovarian. We must keep in mind that there have not been any trials such as this for ovarian cancer - based upon the stunning response of the first woman, the NIH is in the process of expanding the trial and hope to have it up and running by early Spring 2006.

"I am NOT an expert on science, but my VERY basic understanding of the basic science behind this is genes that produce MUC1 are genetically re-created and inserted into a live virus, Then, in what's called the priming stage with the Vaccinia virus (similar to Smallpox), it is injected into the patient. The goal is for the body to produce a robust immune response against the vaccine. As the immune system goes after the virus, it is also getting the engineered MUC1 antigen along with it. As the immune system kills the virus, it is also killing the MUC1 antigen that came in with the virus. It is hoped that the immune system will then begin to recognize MUC1 as a foreign substance in the body. This is followed by the boosting phase in which the patient is given 3 live fowlpox virus injections also carrying the synthetically engineered MUC1. Again, the goal is to generate a robust immune response to the virus so that the immune system goes after it, is exposed to more MUC1, helping the immune system to be boosted further to recognize MUC1 as an invader. The researchers are looking for a T Cell medidated response. In this trial, they are using the entire MUC1 antigen with genetically modified epitopes. What one wants to have happen is the virus causes an inflammatory action making cytokines and other chemical responses that will tip the balance of immunology inside the body to recognize that any overproduction of MUC1 is foreign to the immune system and must be destroyed. Using the FULL or ENTIRE MUC1 antigen as opposed to peptides (fragments) is hoped to allow the immune system to see multiple points of contact. Many vaccines are HLA A2 restricted because they contain peptides and not the full antigen.

"There is a trial getting underway out of Ontario for breast cancer patients, I include the link to that here only for the purposes of clarification about why using a vaccine with the entire antigen may be superior to peptides: this study explains why the MUC1 trial doesn't depend on HLA A2 (MHC1) expression for vaccine efficacy. The NIH (Bethesda, MD) MUC1 vaccine trial also uses the entire MUC1 antigen and not just an epitope from an antigenic determinant or peptide. read the trial intro and you will see what I mean.

TELCYTA™ has been evaluated in Phase 1 and 2 clinical trials in ovarian, non-small cell lung, breast and colorectal cancer. Randomized Phase 3 clinical trials are currently in progress:

1. ASSIST-3 (Assessment of Survival In Solid Tumors-3): A randomized study of TELCYTA plus Carboplatin versus liposomal doxorubicin as second-line therapy in platinum-refractory or platinum-resistant ovarian cancer.

2. ASSIST-1 (Assessment of Survival In Solid Tumors-1): A randomized study of TELCYTA versus liposomal doxorubicin or topotecan as third-line therapy in platinum-refractory or platinum-resistant ovarian cancer.

Information on clinical trials is available at www.clinicaltrials.gov

Physicians and patients seeking additional information on TELCYTA™ clinical trials may send Email to clinicaltrials@telik.com

In November, 2004, reports from phase two clinical trials were very encouraging. The partial and complete remission rate in women with recurrent cancer was 52 percent. Current use of DOXIL, the standard treatment (in combination with platinum and taxol) for recurrent cancer has a response rate of just 12 to 15 percent. TELCYTA works by making ovarian cancer cells return to their vulnerability to standard first line treatment (platinum and taxol administration). More than 100 sites nationwide (USA) are participating in stage three clinical trials.

Telcyta may be available for compassionate use in late 2006 to early 2007 (Anne Helman). Compassionate use is when a drug is just about ready to be FDA approved and a doctor requests its use from the company in order to help a patient who has failed everything else - when they believe that this drug will help.

There is no hair loss with TELCYTA, and it is a one hour transfusion. Side affects are minimal.

Pemtumomab (a human milk fat globule membrane (HMFG), is based on a mouse monoclonal antibody that binds specifically to an abnormal form of mucin (MUC1), a protein found on the surface of cells in many types of solid tumour, including those of the ovary, stomach, lung, breast and prostate. The antibody is attached to the radioisotope Yttrium-90, which irradiates and destroys the cells bound by the antibody and those in close proximity. Three hundred patients were recruited for the phase three trial in 2001.

The launch of Pemtumomab was delayed until at least 2005, because of a tough stance taken by the US Food & Drug Administration on Yttrium-labelled antibodies.

AS1404 (6-dimethylxanthenone-4-acetic acid- DMXAA for short) is a small molecule vascular targeting agent that selectively disrupts blood flow through tumour blood vessels. It is currently in phase I trials. Vascular disrupting agents exert an effect distinct from that of angiogenesis inhibitors, which inhibit the formation of new tumour blood vessels.

The basis for the targeting of tumour blood vessels by AS1404 is thought to lie in the distinctive features of tumour blood vessels: the capillary network is more permeable and less well organised than that of a normal tissue. AS1404 acts directly on the endothelial cells that line tumour blood vessels, causing apoptosis (cell suicide). AS1404 also acts indirectly, causing the release of von Willebrand's factor, which leads to blood clotting and occlusion of blood vessels. In addition, it triggers a local cascade of cytokines (biochemical mediators) including serotonin and tumour necrosis factor (TNF). The direct and indirect effects of AS1404 culminate in the breakdown of the vasculature and the death of tumour cells (haemorrhagic necrosis).

In August 2005, enrollment of patients was completed for a phase II study combining AS1404 with carboplatin and paclitaxel in the treatment of non-small cell lung cancer. Preliminary data were announced from the trial in non-small cell lung cancer on 17 October 2005. Two further phase II trials in ovarian and prostate cancers are also ongoing.

DNA contains genes that are known to suppress tumor growth. Cancer killing strategies include ways to use this knowledge of suppressor genes to stop cancer growth. One of these suppressor genes is called mda-7- it is the active component of INGN 241. Use of the drug has been shown in preclinical trials to increase cancer cell death, and to stimulate immunity against cancer. It is believed that biochemically INGN 241 targets several key pathways that impact the development, growth, and metastasis of cancer cells.

Researchers from nine academic cancer centers concluded that Doxil® (pegylated liposomal doxorubicin) is the first choice for non-platinum-based chemotherapy for relapsed ovarian cancer. The details of this extensive review were published in the January 2005 issue of Gynecologic Oncology.

Women with recurrent ovarian cancer have several options for palliative treatment following failure of taxane and platinum-based chemotherapy. If a recurrence occurs more than six months after remission induction, such patients are classified as platinum-sensitive and tend to respond to repeated platinum-based therapy. Patients who fail induction or relapse within six months of induction therapy are considered to be platinum-resistant and are usually treated with alternative drugs. Drugs that have activity in women with recurrent ovarian cancer include Doxil®, etoposide, Hycamtin® and Gemzar® given as single agents or in combination with other drugs. The optimal therapy for patients with recurrent ovarian cancer has not been determined.

Several advantages were noted in patients treated with Doxil®, such as fewer dose modifications, less frequent treatment for low blood counts and a lower total cost per patient. In addition, Doxil® seemed to produce a survival advantage among patients with platinum-sensitive recurrent ovarian cancer. Other studies, which evaluated cardiac toxicity, were also reviewed and found that Doxil® improved cardiac safety when compared to other drugs within the same class. Based on the survival and side effect advantages and the once-monthly dosing schedule, Doxil® was considered to be the first choice for non-platinum chemotherapy for relapsed ovarian cancer.

In a previous Spanish study, it was concluded that Doxil® was more cost-effective than Hycamtin® for patients with recurrent ovarian cancer and produced equivalent benefits. These authors stated that the costs of the two drugs were equivalent, but that the costs of managing adverse events were higher for the Hycamtin®-treated patients compared to the Doxil®-treated patients. This analysis confirmed an American study published in the Annals of Oncology.

Avastin clinical trials for ovarian cancer were halted in September, 2005 because of unacceptable side affects- gastrointestinal perforations. Patients enrolled were allowed to continue protocol treatment if they desired. One thought is that Avastin was so effective with patients with advanced cancer that when it killed ovarian cancer in the bowel it left perforations in the bowel. Contact Genentech for details.

Genentech and Roche have not given up on Avastin (as of November, 2005) as a useful drug to address ovarian cancer. They now are testing Avastin in patients with less advanced metastasis ("low dose" chemotherapy- also called "metronomic dosing"). Remember however that Avastin kills tumors that are rapidly producing new blood vessels. There is no reason that it would work on microscopic ovarian cancer cells that seed the abdomen.

Pertuzumab is classified as a HER dimerization inhibitor. "HER" refers to "Human Epithelial Growth Factor Receptor". HER pathways regulate cell reproduction. Often cancer cells over-express components of the HER pathways which results in unchecked cell replication (cancer). Dimerization is considered essential for communication from cell to cell along the HER pathways. Pertuzumab interferes with dimerization in cancer cells so that replication is halted.

Phase 1 studies established safe dosages for Pertuzumab and showed that the drug had a partial response in one patient with ovarian cancer. A later study with 58 patients with ovarian cancer was reported at the Chemotherapy Foundation Symposium in 2005. Results from seven patients were reported as follows: one achieved partial disappearance of cancer; 5 achieved stabilization; and one had a mixed response (some tumors grew, other shrunk). Further studies are planned.

. Phase two studies are underway to determine the efficacy of Pertuzumab in combination with Gemcitabine in women with advanced ovarian cancer.

Anne Helman: Gleevec is (may be) a huge disappointment for ovarian cancer- not living up to it's initial hype. I received the same feedback from several others: Gleevec is a disappointment for ovarian cancer patients.

The Phase I clinical study is designed to evaluate the safety and pharmacokinetic profile of MPC-2130 in patients with advanced metastatic tumors or blood cancers as well as refractory cancer that has progressed despite previous chemotherapy. In preclinical studies MPC-2130 demonstrated significant cancer cell killing activity in ovarian cancer, prostate cancer and two lymphoma cell lines, Burkitt's lymphoma and T-cell lymphoma. MPC-2130 was also evaluated in xenograft mouse models of ovarian cancer and prostate cancer. The drug candidate reduced growth of ovarian cancer tumors by 61% relative to controls.

"MPC-2130 is our second investigational drug for cancer to enter the clinic using the apoptotic pathway and fighting cellular proliferation by causing cancer cells to self-destruct. However, our two cancer compounds are very different and function at independent points in the apoptosis pathway," said Adrian Hobden, Ph.D., President of Myriad Pharmaceuticals, Inc. "Not only does each compound demonstrate preclinical attributes that provide it with potentially broad utility in metastatic cancer, but the two drug candidates also display their best potencies against different cancer types."

MPC-2130 was shown to be highly effective in cancer cell lines that are resistant to multiple drugs. Cancer cells may become resistant to chemotherapy through a cellular function that actively purges drugs from the cell. The function is carried out by MDR pumps and is the primary cause of cancers' resistance to many marketed drugs such as paclitaxel and vinblastine. MPC-2130 was tested to determine its susceptibility to MDR pumps, and was shown to be equally effective in anti-cancer activity against the MDR cell lines tested, suggesting that the drug candidate is not a substrate for MDR pumps.

In preclinical studies, PXD101 had a growth-inhibitory activity against a wide range of tumors, including ovarian, and it was effective in specimens resistant to carboplatin and paclitaxel. Alone or in combination, PXD101 could play a significant role in the treatment of solid and hematologic cancer, potentially overcoming some of the resistance mechanisms used by cancer cells.

Anne Helman: Ontak may kill cells that stop immune systems from fighting cancer. As these bad T cells are wiped out, good T cells remain, not necessarily increased in numbers by Ontak, but proportionally more numerous, giving the immune system opportunity to rev up and engage in battle. Phase two studies for ovarian are now open and enrolling. The study location was moved to Baton Rouge after Hurricane Katrina. Denileukin diftitox (Ontak) is a novel recombinant fusion protein approved by the FDA to treat relapsed or refractory cutaneous T-cell lymphoma. It consists of fragments of diphtheria toxin linked to human interleukin-2 and works by targeting the high-affinity interleukin-2 receptor expressed on malignant cells.

Hycamtin has a different mode of action compared to other chemotherapy drugs approved for ovarian cancer. It belongs to a class of drugs known as topoisomerase I (topo-I) inhibitors. Topo-I is produced in the body and is involved in cell division of both normal and cancer cells. In order for cancer cells to divide, which leads to tumor growth, these cells must copy the genetic material contained in their DNA. Treatment with Hycamtin damages DNA, which results in the death of dividing cancer cells and causes therapy-related side effects.

In those situations where cancer recurs after first-line therapy, Hycamtin has demonstrated proven efficacy with mild-moderate nonhematologic toxicities. Many clinicians consider relapsed ovarian cancer to be a chronic disease requiring treatment for the duration of a patient’s lifetime. Hycamtin may be a valuable part of “second-line” treatment during which a number of agents may be used in a carefully monitored sequence.

Topotecan interferes with the growth of cancer cells and slows their growth and spread in the body.

As of May, 2006, Gemzar with carboplatin has been highly critized and is not expected to receive FDA approval.

2006 internet email: "Next we called Novogen, where a spokesman explained that although phenoxodiol is still fast tracked for prostate cancer, the company is concentrating its resources on a clinical trial for ovarian cancer. Phenoxodiol is being tested for women with advanced ovarian cancer as chemo sensitizer along with carboplatin, This is the OVATURE (OVArian TUmor REsponse) Study, official Title: Multi-Center, Randomized, Double-Blind, Phase III Efficacy Study Comparing Phenoxodiol in Combination With Carboplatin Versus Carboplatin With Placebo in Patients With Platinum-Resistant or Platinum-Refractory Late-Stage Epithelial Ovarian, Fallopian or Primary Peritoneal Cancer Following at Least Second Line Platinum Therapy.” The study begins this month (October 2006) and is expected to recruit 470 patients.

Given the realities of clinical trials, a Novogen spokesman told us today, the company believes that by focusing their attention on this ovarian cancer Phase III trial they are following “the shortest route” to FDA approval of phenoxodiol. "

Two Revimid trials were canceled in 2006: in combination with doxil; and in combination with topotecan.

The compound, tricirbine, was tested at various cancer centers from 1982 to 1996 and found to inhibit some cancers, but researchers failed to determine why. The Moffitt-USF team discovered that tricirbine works only against tumors in which the cancer-causing Akt protein is abundant and/or abnormally active. These tumors are addicted to hyperactive Akt and cannot survive without it. Resurrecting tricirbine may be promising for patients with ovarian cancer, for instance, because 40% of women with ovarian cancer have tumors with high levels of active Akt.

VioQuest Pharmaceuticals Inc. (VQPH) of New Jersey is acquiring the licensing rights to the compound from USF through its merger with Greenwich Therapeutics Inc. and is planning clinical trials with Moffitt. The trials are expected to start in 2006. Patients will be selected for the trials based on whether their tumors have hyperactive Akt, which can be determined by a simple slide-stain test of tumor tissue. Because tricirbine has previously been investigated in humans, the hypothesis-driven clinical trials planned at Moffitt can move directly into a PhaseI/II trial.

A phase I clinical trial (2005) was initiated to define the maximum tolerated dose (MTD) and characterize the pharmacokinetic behavior of ARQ 501 administered as a weekly 1-hour intravenous infusion. Eighteen patients received 41 monthly courses of ARQ 501 at doses ranging from 10–550 mg/m2. There was no evidence of drug accumulation or change in disposition upon repeated weekly dosing. A partial response was observed in a patient with uterine leiomyosarcoma who remains on study after 56 weeks of therapy. Two patients achieved stable disease (16 and 32 weeks). Adverse events have been mild, including anemia and fatigue.

Conclusions: Initial dose escalation of ARQ 501 has been achieved without evidence of dose limiting toxicity. Early signs of clinical activity have been demonstrated by partial response and stable disease cases.

April 4, 2006--ArQule, Inc. (Nasdaq: ARQL - News) today reported results from a Phase 1 monotherapy trial with its lead product, ARQ 501, which provided evidence of clinical tolerability and promising anti-tumor activity in cancer patients with advanced solid tumors who had failed prior treatments with chemotherapy.

ARQ 501, the Company's lead product generated from its Activated Checkpoint Therapy(SM) (ACT) platform, is being developed under an alliance with Roche. ACT compounds are designed to selectively and broadly target cancer cells through activation of checkpoint pathways. ARQ 501 activates E2F1-mediated checkpoint pathways, resulting in apoptosis (cell suicide) in cancer cells selectively.

Based on data from Phase 1 trials, the Phase 2 development plan for ARQ 501 has been established and will include monotherapy trials in leiomyosarcoma and head and neck cancer, as well as combination therapy trials with gemcitabine in pancreatic cancer and with paclitaxel in ovarian cancer.

Phase I trial in solid tumors, Ph I/II in NSCLC (non-small cell lung cancer), and Ph I/II in ALL (acute lymphocytic leukemia) are ongoing. Ph II trials in cervical, endometrial, ovarian cancers forthcoming.

Å6 consistently shows efficacy across cancers, indicating that it is addressing a fundamental pathway for proliferative and invasive diseases. The favorable biological activity of Å6 has been demonstrated in in vitro models of cell migration, invasion and angiogenesis, as well as, in animal models including breast, prostate and brain tumors; also in models of ocular disease in rodents and monkeys.

Results from a completed Phase 1a safety clinical trial in humans showed there were no systemic drug-related adverse events in healthy volunteers. The Company has also successfully completed enrollment of patients with advanced gynecologic cancer in a Phase 1b clinical trial. To date, there have been no drug related serious adverse events and > 40% patients dosed continuously with Å6 experienced disease stabilization. Based on the encouraging Phase 1 results, Ångstrom is currently (2006) enrolling patients with asymptomatic CA125 progression of ovarian cancer (“marker-only relapse”) in a randomized, double-blind, placebo-controlled Phase 2 clinical trial.