NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS

The NCDDG Program, established in 1983, supports broad, innovative, multi-disciplinary approaches to the discovery of new, synthetic or natural-source derived anticancer drugs. Although this program does not support clinical trials, a timely evaluation of products discovered by the Groups is encouraged. The NCDDGs are funded as cooperative agreements in response to a Request for Applications (RFA). A cooperative agreement is a funding mechanism used when the work is investigator initiated but significant involvement of the Government is anticipated in performance of activities.


Past Issuances:

National Cooperative Drug Discovery Groups for Cancer, RFA CA-05-001, NIH Guide, January 16, 2004 (Letter of Intent Receipt Date: April 19, 2004; Application Receipt Date: May 19, 2004)
(Closed: 05/20/04)
This RFA is a reissuance of RFA-CA-99-010, which was published in the NIH Guide on April 14, 1999


Current Awardees:

No./Expiration Date

P.I./Institution

Title

Collaborators

U19 CA52955

08/01/05-04/30/10 Abstract/Programs 		Phillip O. Crews, Ph.D.
University of California, Santa Cruz, CA 		Targeted Discovery of Marine-derived Anticancer Leads Robert Schlege, Novartis Institutes of Biomedical Research, Inc.; William H. Gerwick, Oregon State Univ.; Amy E Wright, Harbor Branch Oceanographic Institute; William Fenical, Scripps Institute of Oceanography

U19 CA67786

09/26/05-04/30/2010 Abstract/Programs 		Chris M. Ireland, Ph.D.
University of Utah, Salt Lake City, UT 		Anticancer Agents from Unique Natural Products Sources Lee Greenberger, Guy Carter, Semirami Ayral-Kaloustian, Wyeth Pharmaceuticals; John H. Clardy, Harvard Univ.; Raymond J. Andersen, Univ. of British Columbia

U19 CA11341

09/09/05-04/30/2010
Abstract/Programs 		Elizabeth M. Jaffee, M.D.
Johns Hopkins University, Baltimore, MD 		Combinational Immunotherapies to Amplify Vaccine Induce* T.C. Wu, Drew Pardoll, Lieping Chen, Johns Hopkins Univ.

U19 CA113298

08/19/05-04/30/2010 Abstract/Programs 		Kit S. Lam, M.D.
University of California-Davis, Sacramento, CA 		Targeting Agents for Human and Canine Lymphoma Yoshikazu Takada, Sally DeNardo, Univ. of California-Davis

U19 CA52995

09/29/05-04/30/2010 Abstract/Programs 		Garth Powis, D. Phil
Arizona Cancer Center, Tucson, AZ 		Cancer Drugs Active Against Stress Signaling Pathways Robert T. Abraham, Peter Houghton, Mary-Ann Bjornsti, St. Jude Children's Hospital; John S. Lazo, Univ. of Pittsburgh

U19 CA113318

08/15/05-04/30/2010 Abstract/Programs 		John C. Reed, M.D.
Burnham Institute, La Jolla, CA 		Apoptosis-Based Cancer Drug Discovery Dennis Carson, Univ. of California San Diego; Maurizio Pellechia, The Burnham Institute

U19 CA67771

05/27/05-04/30/2010 Abstract/Programs 		Saïd M. Sebti, Ph.D.
H. Lee Moffitt Cancer Center & Research Institute, Drug Discovery Program, Tampa, FL 		Inhibitors of Rho Function as Novel Cancer Therapeutics Andrew D. Hamilton, Yale Univ.; Nicholas J. Lawrence, Moffitt Cancer Center; Adrienne Cox and Channing Der, Univ. of North Carolina at Chapel Hill

U19 CA113297

06/21/05-04/30/2010 Abstract/Programs 		Ben Shen, Ph.D.
University of Wisconsin-Madison, Madison, WI 		UWCCC National Cooperative Drug Discovery Group for Cancer Jon S. Thorson, Paul F. Lambert, F. Michael Hoffman, Univ. of Wisconsin

U19 CA113317

07/01/05-04/30/2010 Abstract/Programs 		Shaomeng Wang, Ph.D.
University of Michigan, Ann Arbor, MI 		Novel Small-Molecule Inhibitors of Bcl-2/Bcl-xL Protein* Jeanne Stuckey, Kenneth J. Pienta, Univ. of Michigan

Four Marketed Agents with Substantial Input from NCDDG Program

Product:

Hycamtin (Topotecan HCl)

NCDDG Grantee:

Dr. Warren Ross, U of Florida at Gainesville

Company Partner:

SmithKline Beecham (now GlaxoSmithKline)

NCDDG Funding Years:

1985 - 1990

Year of First FDA Approval:

1996 (11 years after start of funding)

Indications (2007):

Ovarian, small cell lung, and cervical cancers

Comments:

Hycamtin is an inhibitor of topoisomerase I, an enzyme involved in replication, recombination and repair of DNA. Inhibiting this enzyme leads to DNA damage and apoptosis. Hycamtin is a semi-synthetic, water- soluble analog of the natural product camptothecin. It is available in both oral and iv dosage forms.

Return on Investment:

Sales of $160 million in 2006


Product:

Gliadel

NCDDG Grantee:

Dr. Henry Brem, Johns Hopkins University, Baltimore, MD

Company Partner:

Guilford Pharmaceuticals (now MGI Pharma, Inc.)

NCDDG Funding Years:

1990 - 2005

Year of First FDA Approval:

1996 (6 years after start of funding)

Indications (2007):

Glioblastoma multiforme

Comments:

This product consists of BCNU (carmustine) impregnated in a wafer composed of a polyanhydride biodegradable polymer invented by Dr. Robert Langer of MIT. Wafers are implanted at the time of surgical resection of the tumor. Over time the drug diffuses away from the polymer, which degrades. This was the first agent approved to treat brain tumors in 20 years at the time of its approval. Gliadel is also being evaluated in combination with O6-Benzylguanine (O6BG), an inhibitor of repair of DNA adducts by alkylguanine transferase. O6BG is an investigational agent developed by the NCDDG led by Dr. Anthony Pegg.

Return on Investment:

Sales of $35.8 million in 2006


Product:

Ontak (Denileukin Diftitox)

NCDDG Grantee:

Dr. John Murphy, The University Hospital, Boston, MA

Company Partner:

Seragen, Inc. (NCDDG) followed by Ligand Pharmaceuticals, Inc.(now Eisai)

NCDDG Funding Years:

1988 - 1998

Year of First FDA Approval:

1998 (10 years after start of funding)

Indications (2007):

Cutaneous T cell lymphoma

Comments:

This fusion protein, the only one in clinical use, is composed of the catalytic and transmembrane domains of diphtheria toxin and IL-2. The product induces remissions in lymphomas that express the CD25 component of the IL-2 receptor. On June 4, 2007, Eisai announced that Ontak achieved a 49.1% overall response rate in a Phase III trial of CTCL and showed an extension in progression-free survival. These preliminary results were from the largest randomized, placebo-controlled clinical trial ever conducted in this orphan disease for which there is no known cure.

Return on Investment:

Sales of $34.3 million in 2003


Product:

Erbitux (Cetuximab)

NCDDG Grantee:

Dr. John Mendelsohn, MD Anderson, Houston, TX (formerly of Memorial Sloan-Kettering, New York, NY)

Company Partner:

ImClone Systems, In. and Bristol-Myers Squibb Co.

NCDDG Funding Years:

1985 - 1998

Year of First FDA Approval:

2004 (19 years after start of funding)

Indications (2007):

Colorectal and Head & Neck cancers

Comments:

This anti-EGF receptor antibody (C225) is a recombinant, human-mouse chimeric monoclonal antibody that binds specifically to the extracellular domain of the human epidermal growth factor receptor (EGFR). Is composed of the Fv regions of a murine anti-EGFR antibody with human IgGI heavy and kappa light chain constant regions. Erbitux is the first FDA-approved agent for head & neck cancer in 45 years. It was approved based on its ability to extend survival in combination with radiation. It was also approved as monotherapy to treat head and neck cancer that has metastasized. It was approved to treat colorectal cancer as monotherapy or in combination with irinotecan.

Return on Investment:

First Quarter 2007 Global Net Sales of $306.1 million and $160.1 million in sales in the US market

Investigational New Drugs with Substantial Input of the NCDDG Program, 1984 to 2007

(Excludes 4 Marketed Agents)
Total Count: 21

Agent

N1,N 14-diethylhomospermine

  • Polyamine analog synthesized by Raymond Bergeron on Carl Porter NCDDG.
  • Disrupts polyamine homeostasis.
  • Diethylhomospermine (DEHOP) evaluated in a Phase II trial in AIDS patients with uncontrolled, refractory diarrhea; licensed by SunPharm.
  • SunPharm was acquired by GelTex on 8/17/1999. DEHOP placed on hold on 1/13/2000 while side-effects were examined. On 12/14/2000 Genzyme Corp acquired GelTex. Development of DEHOP was not continued.

N1,N 11-diethylnorspermine

  • Polyamine analog synthesized by Raymond Bergeron on Porter NCDDG.
  • Disrupts polyamine homeostasis.
  • Diethylnorspermine entered Phase II clinical trials for the treatment of multiple types of solid tumors at Roswell Park, U of Florida, and Johns Hopkins University; licensed by Parke-Davis.
  • Now licensed by Genzyme Corporation. Drug received Orphan Drug Designation on 5/25/2004 for the treatment of hepatocellular carcinoma. Clinical trials in liver cancer are in progress.

O6-Benzylguanine (OBG)

  • Identified and evaluated by the NCDDG guided by Anthony Pegg, The Milton S. Hershey Medical Center.
  • Selected from a series of compounds synthesized by Robert Moschel at NCI Frederick.
  • Entered NCI-sponsored clinical trials in combination with BCNU as a means of blocking repair of DNA adducts by alkylguanine transferase, a protein responsible for a major mechanism of resistance to BCNU and similar agents.
  • Collaborated with Brem NCDDG in combination studies with Gliadel.
  • Two brain tumor studies are recruiting as of 2/26/2008 (Clinical Trials.gov site).

Cryptophycin

  • Novel depsipeptide isolated by the late Robert Moore, University of Hawaii, from blue-green algae on the Fred Valeriote NCDDG.
  • Found to have potent antiproliferative and antimitotic properties that differ from those of Taxol.
  • A semi-synthetic analog, Compound #52, entered Phase II clinical trials under sponsorship of Eli Lilly. Lilly chemists developed a total synthesis procedure in collaborative effort between natural product and medicinal chemists.
  • Lilly closed their IND. However, Sanofi licensed the cryptophycins from Wayne State University in 12/2007. Second generation analogs have been identified with less peripheral neuropathy; one is expected to be selected for development.

Cordycepin and Deoxycoformycin

  • Entered Phase I clinical trials for eventual treatment of lymphoblastic leukemias and lymphomas that contain terminal deoxynucleotidyl transferase (TdT), a unique DNA polymerase that catalyzes the polymerization of deoxyribonucleotides on 3'-hydroxyl ends of preformed oligo- or polydeoxynucleotide initiators, without the need of a template. Cordycepin inhibits TdT if its own metabolism is blocked by deoxycoformycin, an inhibitor of adenosine deaminase. Developed clinical assay.
  • Project was conceived and brought to trial by the NCDDG headed by Ronald McCaffrey, The University Hospital, Boston, MA found that cordycepin activated an apoptotic cascade and had antifungal properties.
  • First licensee was Oxigene. License for cordycepin is now held by OncoVista through a merger with Aengus Pharmaceuticals in January 2006. Currently in Phase I/II clinical trial in patients with acute lymphoblastic leukemia (ALL) who express the enzyme TdT.

Murine Anti-Transferrin Receptor Monoclonal Antibodies (A27,15/E2.3)

  • The product consisted of a pair of murine IgG1 monoclonal antibodies directed against the human transferrin (Tf) receptor identified on the John Mendelsohn NCDDG by Ian Trowbridge, Salk Institute.
  • Entered Phase IA clinical trails at the University of Arizona in Tucson under the supervision of Dr. Raymond Taetle.
  • Antibodies were administered as a combination in a 1:1 ratio based on preclinical studies that showed that the most effective inhibition occurred when the products were given as a pair, presumably by cross-linking the transferrin receptor.
  • Product was produced by the Biopharmaceutical Development Program at NCI-Frederick with oversight by the Biological Resources Branch.
  • IND was held by NCI; closed in 2001 due to toxicity.

A Farnesyl Transferase Inhibitor

  • Developed by the NCDDG headed by Said Sebti, University of South Florida, Tampa, FL.
  • Based on the peptide structure of CAAX box, a series of peptidomimetics were synthesized and evaluated.
  • This Group was the first to publish the antitumor properties of this class of compounds in human xenograft models and to demonstrate, contrary to initial hypotheseshypothesis, that the ras protein is probably not the target or the determinant of antitumor activity.
  • One derivative entered Phase I clinical trials under sponsorship of Abbott Laboratories, but the IND was closed when orally administered drug did not achieve required blood levels.

Provenge, A Vaccine for Prostate Cancer

Sipuleucel-T (APC-8015)

  • Developed by Dr. Riner Laus, Dendrion Corp., Seattle, WA, on Ronald Levy’s NCDDG.
  • The approach is to isolate a patient’s dendritic cells, pulse them with a peptide derived from prostatic acid phosphatase, and re-administer the modified dendritic cells back to the patient.
  • On 2/17/2005, Dendreon Corp. announced survival advantage in men with asymptomatic, metastatic androgen-independent prostate cancer.
  • However, on 3/28/2007, FDA stated that Provenge failed both primary and secondary endpoints in two separate trials.
  • On April 14, 2009, Dendrion announced that a pivotal Phase III trial achieved the pre-specified level of statistical significance in improvement of overall survival. The company is awaiting a final decision from FDA.

Betulinic Acid

  • A pentacyclic triterpene isolated from bark of white birch trees by the Douglas Kinghorn NCDDG.
  • Developed for treatment of melanomas based on NCDDG data and findings of Tapas K. Das Gupta using primary human cultures. Appears to induce apoptosis.
  • Clinical product developed by NCI RAID program.
  • In Phase I-II trials as 20% betulinic acid ointment for treatment of dysplastic nevi in prevention trial.

HTI-286

WAY-174286

  • Developed on the NCDDG headed by Chris Ireland and taken to clinical trial by their industrial partner Wyeth-Ayerst; totally synthetic analog of hemiasterlin, a tripeptide from a marine sponge.
  • Tubulin binder at Vinca site with activity in Taxol-resistant cells. Poor substrate for P-glycoprotein.
  • IND closed by Wyeth-Ayerst after limited Phase I-II trials in non-small cell lung cancer (corporate decision). Ongoing negotiations to re-open the IND with another sponsor.

LAF389

  • Developed on the Phillip Crews NCDDG and taken to clinical trial in Europe by the industrial partner, Novartis. Is a semi-synthetic analog of Bengamide B, which was isolated by the NCDDG from the marine sponge Jaspidae.
  • Inhibitor of methionine amino peptidase 2 (MetAP2) with anti-angiogenic properties.
  • IND closed after a Phase I and pharmacokinetic study due to unpredictable cardiovascular events and lack of clinical response.

LAQ824

  • Developed on the Phillip Crews NCDDG as a result of a medicinal chemistry program by Novartis, their industrial partner. Novartis tried to mimic the histone deacetylase inhibitory activity of psammaplin A, which had been isolated on the NCDDG but was found to have poor physiologic stability.
  • Developed to clinical trial in Europe by Novartis as a Class I/II HDAC inhibitor (same class as SAHA, which is now marketed).
  • Phase II trials were discontinued by Novartis. Some cardiac toxicity was noted (EKG changes and dose-related increases in QTcF).

PX-478

  • This first-in-class inhibitor of hypoxia inducible factor HIF-1 alpha, a transcription factor that controls the expression of genes in cancer cell growth and survival, was developed on the Garth Powis NCDDG.
  • This orally-administered agent entered clinical trial in late 2007 in patients with advanced solid tumors or lymphomas. The licensee is Biomira, Inc., Edmonton, Canada (renamed Oncothyreon in 12/2007).

PX-12

  • The Garth Powis NCDDG developed this first-in-class irreversible thioredoxin-1 (Trx-1) inhibitor, which entered clinical trial in 2002.
  • Trx-1 is a small redox protein that is over-expressed in many human tumors and is associated with aggressive tumor growth and decreased patient survival.
  • Now in Phase 1B trial for long-term infusion and in Phase II trial in pancreatic cancer under sponsorship of Prolx (now under control of Oncothyreon), the industrial NCDDG partner. A Phase II trial in colorectal cancer will start soon.
  • In human trials, PX-12 decreased plasma Trx-1 levels and VEGF levels.

PX-866

  • Powis NCDDG is developing this PI-3 Kinase inhibitor. Powis discovered and patented Wortmannin as a PI-3 Kinase inhibitor and then developed this second generation product, which has less toxicity in animal testing.
  • Assisted with early preclinical studies by the NCI RAID program (RAID I).
  • Licensed to ProlX, their pharmaceutical partner that became a wholly owned subsidiary of Biomira. In December 2007 Biomira moved from Canada to Bellevue, WA in the US and changed its name to Oncothyreon.
  • In Phase I clinical trial in patients with solid tumors.

CSR-207

  • This vaccine was developed on the Elizabeth Jaffee NCDDG to target Mesothelin-expressing tumors, such as malignant epithelial mesothelioma, adenocarcinoma of the pancreas, non-small cell lung carcinoma, and adenocarcinoma of the ovaries.
  • The vaccine consists of an attenuated, live form of Listeria monocytogenes expressing human Mesothelin. The product has been genetically modified with recombinant DNA to release the Mesothelin antigen. CSR-207 boosts an immune response to Mesothelin. Product was approved by the RAC and the FDA for trial.
  • In monkey studies, this product broke T cell tolerance against Mesothelin.
  • A Phase I study began in 12/2007 and is now recruiting patients. The study is sponsored by Anza Therapeutics, Inc. Ampicillin is given for 10 days after the last dose of CSR-207 to block potential infections.

pNGVL4a-HPV-16 E7(detox)/HSP70

  • This vaccine was developed on the Elizabeth Jaffee NCDDG to target the treatment of patients with HPV 16-positive head and neck tumors.
  • Production assistance was provided by the NCI Biopharmaceutical Development Program at NCI-Frederick with oversight by the Biological Resources Branch.
  • A Phase I clinical trial of the safety and immunogenicity of repeated vaccination with this product is in progress in patients with Stage III or IV HPV 16-positive head and neck squamous cell carcinoma (HNSCC).

pNGVL4a-Sig/E7(detox)HSP70

  • This vaccine was developed on the Elizabeth Jaffee NCDDG to target the treatment of patients with HPV 16-positive cervical tumors.
  • Production assistance was provided by the NCI Biopharmaceutical Development Program at NCI-Frederick with oversight by the Biological Resources Branch.
  • A Phase I/II clinical trial is in progress for the treatment of patients with HPV 16-positive cervical intraepithelial neoplasia 3 (CIN3).

CRS-100

  • The NCDDG headed by Elizabeth Jaffee developed Listeria as a targeting agent for liver metastases and licensed the technology to the Cerus Corporation. Product The product consists of a live-attenuated strain of Listeria monocytogenes. CRS-100 is attenuated by genetic modification to limit cell to cell spread and invasion of liver cells. The product has less virulence but retains the ability to stimulate immunity in mice and generate anti-tumor activity.
  • CRS-100 is the parent vector (bare vector without antigen, such as mesothelin). The FDA required safety testing of the vector alone over concern that injected patients may transmit a Listeria infection to children or those with compromised immunity. Are seeing fevers in patients.
  • On 11/20/2007, Cerus entered into an agreement with Anza Therapeutics, Inc. to transfer certain assets and license agreements, including this one.
  • A Phase I study is currently enrolling patients with liver metastases under sponsorship of Anza.

GRN163L

  • This NCDDG led by Alison Chen at the Geron Corporation searched for inhibitors of telomerase, a high risk project.
  • Identified and evaluated a short chain phosphorothioate coupled to a lipid; targets the RNA at catalytic site of the enzyme.
  • Clinical trials are ongoing.

Ch14.18

  • This chimeric mouse/human monoclonal antibody was developed and evaluated on the Ralph Reisfeld NCDDG at Scripps.
  • This Mab binds to the ganglioside GD2 and induces antibody-dependent cell-mediated cytotoxicity and complement- dependent cytotoxicity against GD2-expressing tumor cells. GD2 is overexpressed in malignant melanoma, neuroblastoma, osteosarcoma, and small cell carcinoma of the lung.
  • Anti-tumor effects due to granulocyte-mediated, antibody-dependent cell-mediated cytotoxicity (ADCC).
  • Product was produced by the Biopharmaceutical Development Program at NCI-Frederick with oversight by the Biological Resources Branch.
  • The Children’s Oncology Group determined that immunotherapy – a combination of ch14.18 antibody, IL-2 and GMCSF – and Isotretinoin (also known as cis-retinoic acid) more effectively reduces the risk that neuroblastoma in children will grow back than treatment with Isotretinoin alone (trial protocol ANBL0032). Also, the immunotherapy increases the chance of survival after completion of stem cell transplantation therapy.
  • It is expected that this new immunotherapy, based in part from NCDDG supported research, will become first line therapy for high risk neuroblastoma in children.

Hu14.18-Interleukin-2 Fusion Protein

  • This human monoclonal antibody, also developed on discovered in the Ralph Reisfeld NCDDG, is combined with interleukin-2. The Mab binds to the cancer cells and delivers IL-2, which stimulates the immune system to destroy the cancer cells.
  • Product was produced by the Biopharmaceutical Development Program at NCI-Frederick with oversight by the Biological Resources Branch.
  • Currently recruiting patients for a Phase II trial in melanoma. Are two active trials (one Phase I and one Phase II) in neuroblastoma. Paul Sondel, U. of Wisconsin, and collaborators are coordinating the studies. Trials are sponsored by NCI, but negotiations are taking place with Merck/Serono.

IL-7

  • John Murphy, Boston University produced IL-7 on his NCDDG devoted to the preparation of fusion proteins including interleukins such as IL-7.
  • IL-7 was produced by the Biopharmaceutical Development Program at NCI-Frederick with oversight by the Biological Resources Branch. BDP developed a production and purification strategy that was scaled up by the owner, Sanofi/Cytheris, using a Cooperative Research and Development Agreement (CRADA) in support of multiple intramural and extramural clinical trials.
  • IL-7 may stimulate the white blood cells to kill tumor cells; now in an NCI-sponsored Phase I trial in kidney cancer.
  • IL-7 was shown in a Phase I/II study to improve CD4 T-cell counts in chronically infected HIV-1 patients; now in other trial in HIV-infected patients under sponsorship of the National Institute of Allergy and Infectious Diseases.
  • IL-7 is also in clinical trial in cancer patients along with IL-2 and a dendritic cell vaccine to boost CD4 T-cell counts.

Former Awardees:

No./Performance

Period

P.I./Institution

Title

Collaborators

U19 CA52857

06/15/90-04/30/05 Abstract/Programs 		Henry Brem, M.D.
Johns Hopkins School of Medicine
Baltimore, MD 		Controlled Release Polymers for Brain Tumors Drew Pardoll, Johns Hopkins; O. Michael Colvin, Duke Univ. Medical Center; Robert S. Langer, MIT; W. Mark Saltzman, Yale Univ.

U19 CA67842

09/20/95-09/30/04 Abstract/Programs 		Allison C. Chin, Ph.D.
Geron Corporation
Menlo Park, CA 		Telomerase: A Molecular Target for Cancer Therapy Richard L. Tolman, Geron Corp.; Malcolm A.S. Moore, Memorial Sloan-Kettering Cancer Ctr.

U19 CA52955

09/01/90-04/30/05 Abstract/Programs 		Phillip Crews, Ph.D. University of California, Santa Cruz Santa Cruz, CA Molecular Approaches to Discover Marine Natural Product Anticancer Leads Dennis France, Novartis Institute for Biomedical Research; William H. Gerwick, Oregon St. U.; Amy E. Wright, Harbor Branch Oceanographic Institute

U19 CA67775

09/08/95-04/30/05 Abstract/Programs</ 		William Fenical, Ph.D.
Scripps Institution of Oceanography
University of California, San Diego, La Jolla, CA 		New Anticancer Drugs from Cultured and Collected Marine Organisms D. John Faulkner, Scripps Inst. of Oceanography, UCSD; Yuzuru Shimizu, U. of Rhode Island; Robert Kramer, Bristol-Myers Squibb Pharmaceutical Research Institute

U19 CA87427

09/27/00-04/30/05 Abstract/Programs 		Jose A. Halperin, M.D.
Harvard Medical School
Laboratory for Membrane Transport, Boston, MA 		New Translation Initiation Inhibitors for Cancer Therapy William Christ, Gerhard Wagner, Harvard Medical School

U19 CA50771

09/29/89-05/31/05 Abstract/Programs 		Sidney M. Hecht, Ph.D.
University of Virginia
Charlottesville, VA 		Natural Products Discovery - Nuclear & Signaling Targets John S. Lazo, U. of Pittsburgh; David G. I. Kingston, VPI & State U.; Steven C. Bobzin, Galileo Laboratories

U19 CA67786

09/08/95-04/30/05 Abstract/Programs 		Chris M. Ireland, B.A., Ph.D.
University of Utah
Salt Lake City, UT 		Anticancer Agents from Unique Natural Products Sources Philip Frost, William M. Maiese, Jerauld S. Skotnicki, Wyeth-Ayerst Research; Jon. C. Clardy, Harvard; Raymond J. Andersen, U. of British Columbia

U19 CA72108

09/30/96-04/30/04 Abstract/Programs 		Elizabeth Marion Jaffee, M.D.
Johns Hopkins University School of Medicine
Baltimore, MD 		Antigen-Specific Vaccines for Breast Cancer Drew Pardoll, Tzyy-Choou Wu, Johns Hopkins; Yvonne Paterson, Univ. of Pennsylvania School of Medicine

U19 CA52956

09/01/90-04/30/05 Abstract/Programs 		Alan Douglas Kinghorn, Ph.D., D.Sc., Univ. of Illinois at at Chicago, Chicago, IL Novel Strategies for Plant-Derived Anticancer Agents Norman R. Farnsworth, U. of Ill. at Chicago; Mansukhlal C. Wani, RTI; Robert A. Kramer, Bristol-Myers Squibb Pharmaceutical Research Institute

U19 CA87525

9/30/00-05/31/05 Abstract/Programs 		Alfred H. Merrill, Jr., Ph.D.
Georgia Institute of Technology
Atlanta, GA 		Naturally Occurring Sphingolipids and Spingolipid Analogs as Mechanism-based Anti-cancer Agents Dennis C. Liotta, David Pallas, Emory Univ.

U19 CA67763

9/08/95-04/30/05 Abstract/Programs 		William Booth Parker
Southern Research Institute
Birmingham, AL 		Tumor Sensitization to Purine Analogs by E. coli PNP Steven E. Ealick, Cornell Univ.; John A. Secrist, III, Southern Research Institute; Eric J. Sorscher, U. of Alabama at Birmingham

U19 CA52995

08/08/90-04/30/05 Abstract/Programs 		Garth Powis, D. Phil
Arizona Cancer Center
Tucson, AR 		Anticancer Drugs Active Against Cell Cycle and Signal Pathways Targets Robert Abraham, Burnham Institute; John Lazo, Univ. of Pittsburgh

U19 CA67771

09/01/95-04/30/05 Abstract/Programs 		Saïd M. Sebti, Ph.D.
Lee Moffitt Cancer Center & Research Institute, Drug Discovery Program,
Tampa, FL 		Geranylgeranyltransferase I Inhibition and Cancer Therapy Andrew D. Hamilton, Yale Univ.; Adrienne Cox, Univ. of North Carolina

U01 CA45967

09/03/87-05/31/92 		Michael G. Brattain, Ph.D.
Baylor College of Medicine
Houston, TX 		Growth Regulation of Human Colonic Neoplasms J.K.V. Willson, Case Western Reserve Univ.; Y.S. Kim, Univ. of CA at San Francisco; L.C. Yeoman, Baylor College of Medicine; Bristol-Myers Squibb Co.

U01 CA50743

7/15/89-04/30/94 		Ching-jer Chang, Ph.D.
School of Pharmacy, Purdue University
Lafayette IN 		Mechanism-Based Discovery of Antitumor Agents Curtis L. Ashendel, Robert L. Geahlen, Purdue Univ.

U01 CA50750

09/01/89-06/30/94 		Jon C. Clardy, Ph.D.
Cornell University
Ithaca, NY 		New Anticancer Drugs from Cultured and Collected Marine Organisms Anna-Maria Casazza, Bristol-Myers Co.; D. John Faulkner, William Fenical, Scripps Inst. of Oceanography; Chris Ireland, Univ. of Utah; Yuzuru Shimizu, Univ. of Rhode Island

U01 CA45962

09/10/87-07/31/90 		Thomas H. Corbett, Ph.D.
Wayne State University, School of Medicine
Detroit, MI 		Drug Discovery - Anticancer Agents for Colorectal Cancer Paul Cavanaugh, Eastman Kodak/Sterling Drug (replaced Paul Aristoff and Pat McGovern, The Upjohn Co.); Frederick Valeriote, Gordon Luk, Wayne State Univ.

U01 CA52956

09/30/90-09/29/95 		Geoffrey A. Cordell, Ph.D.
Univ. of Illinois at Chicago,
Chicago, IL
(replaced by: A. Douglas Kinghorn) 		Novel Strategies for Plant-Derived Anticancer Drugs Norman R. Farnsworth, A. Douglas Kinghorn, John M. Pezzuto, Univ. of Ill. at Chicago; Monroe E. Wall, Research Triangle Inst.; Timothy J.R. Harris, Glaxo Group Research Ltd.

U01 CA57714

09/30/92-09/29/95 		J. Gordon Foulkes
Oncogen Science, Inc.
Uniondale, NY 		Development of Novel Drugs for PH1 Positive Leukemia Collin Goddard, Oncogen Science, Inc.; Barry Katz, MYCOsearch, Inc.; John A. Slack, Aston Molecules, Ltd.; John Groffen, Children’s Hospital of Los Angeles; Richard Van Etten, Center for Blood Research

U01 CA51880

06/07/90-05/31/95 		L. L. Houston, Ph.D.
Cetus Corp.
Emeryville, CA 		Engineered Antibreast Cancer Single-Chain FV Immunotoxin James S. Huston, Creative BioMolecules; Louis M. Weiner, Fox Chase Cancer Ctr.; Walter F. Stafford, Boston Biomedical Research Ctr.

U01 CA46088

09/30/87-05/31/92 		Michael R. Johnston, M.D.
Univ. of Colorado Health Sciences Ctr.
Denver, CO 		National Cooperative Drug Discovery Group for Lung Cancer Paul A. Bunn, Univ. of Colorado Health Sciences Ctr.; Christopher A. Dawson, Zablocki V.A. Medical Ctr.; Edward L. Gillette, Colorado State Univ.

U19 CA 53617

05/01/90-09/29/01 		Victor A. Levin, M.D.
University of Texas/M.D. Anderson Cancer Center
Houston, TX 		Development of Drug Inhibitors of Src John S. McMurray, Raymond Budde; Robert Newman, Gary Gallick, U. of Texas, M.D. Anderson Cancer Ctr.; Johnathon Ellman, Univ. of Calf, Berkley

U01 CA 37655

08/01/84-1988 		Victor A. Levin, M.D.
Northern California Cancer Center 		Approaches to Inhibition of Oncogene Expression J. Michael Bishop, George Kenyon, U. of California, San Francisco; Paul Bartlett, U. of California, Berkeley; David Stringfellow, Bristol-Myers

U19 CA72103

9/30/96-09/30/01 		Ronald Levy, M.D.
Stanford Univ. Medical Center
Stanford, CA 		GM-CSF Fusion Proteins and Dendritic Cells as Tumor Vaccines Edgar G. Engleman, Stanford Univ.; Reiner Laus, Activated Cell Therapy

U01 CA51908

05/21/90-04/30/95 		Marc E. Lippman, M.D.
Lombardi Cancer Research Center, Georgetown University
Washington, D.C. 		Growth Regulation as Targets in Breast Cancer Treatment Mary Beth Martin, Edward A. Sausville, Robert Clarke, Anton Wellstein, Robert Dickson, Georgetown Univ.

U01 CA52020

06/01/90-05/31/93 		Ronald P. McCaffrey, M.D.
University Hospital, Boston University, Boston, MA 		Specific Therapy for TdT-Positive Leukemia/Lymphoma G. Peter Beardsley, Yale Univ. School of Medicine; Chung K. Chu, Univ. of Georgia

U01 CA51992

06/15/90-05/31/95 		Frank McCormick, Ph.D.
Cetus Corporation
Emeryville, CA 		Discovery of Drugs Inhibiting Oncogenic RAS Proteins Alfred Wittinghofer, Max Planck Inst.; Alfred Redfield, Brandeis Univ.; Alexander W. Wood, Hoffmann-LaRoche

U19 CA37641

08/01/85-08/31/98 		John Mendelsohn, M.D.
Univ. of Texas, M.D. Anderson Cancer Ctr.Houston, TX
(replaced by: Raymond Taetle
University of Arizona,
Tucson, AZ) 		Antireceptor Monoclonal Antibodies in Cancer Treatment Ralph A. Reisfeld, The Scripps Research Inst.; Raymond Taetle, Univ. of Arizona; Ian S. Trowbridge, The Salk Inst. of Biological Studies; Hideo Masui, Memorial Sloan-Kettering

U19 CA48626

09/01/95-08/31/98 		John R. Murphy, Ph.D.
University Hospital, Boston University,
Boston, MA 		IL-7 & IL-7R Targeted Therapeutic Agents for Leukemia Francine Foss, Boston Univ. Medical Ctr. Hospital; Benjamin Rich, Brigham & Women’s Hospital; Cory A. Waters, Seragen, Inc..
U19 CA48626
09/30/88-07/31/93 		John R. Murphy, Ph.D.
University Hospital, Boston
University, Boston, MA 		Growth Factor Receptor Targeted Toxins for Leukemia/Lymphoma Ronald McCaffrey, Univ. Hospital, Boston U.; Terry B. Strom, Beth Israel Hospital; Vicki E. Kelley, Brigham & Women’s Hospital; Jean Nichols, Seragen Corp.
U19 CA72108
09/30/96-09/29/00 		Drew M. Pardoll, M.D., Ph.D.
Johns Hopkins University,
Baltimore, MD 		Antigen Specific Vaccines for Breast and Cervical Cancer T.C. Wu, Elizabeth Jaffe, John Hopkins; Yvonne Paterson, U. of Pennsylvania

U19 CA57725

08/17/92-09/29/01 		Anthony E. Pegg, Ph.D.
Penn State University
Hershey, PA 		Inhibition of DNA Repair to Enhance Chemotherapy M. Eileen Dolan, The Univ. of Chicago Medical Ctr; Henry S. Friedman, Duke Univ. Medical Center; S. Clifford Schold, Univ. of Texas Southwestern Medical Ctr.; Stanton L. Gerson, Case Western Reserve Univ.

U01 CA37606

09/01/84-08/31/92 		Carl W. Porter, Ph.D.
Grace Cancer Drug Center, Roswell Park Memorial Inst.
Buffalo, NY 		Inhibitors of Polyamine Biosynthesis and/or Function Raymond J. Bergeron, Univ. of Florida at Gainesville; James K. Coward, Rensselaer Polytechnic Inst.; Janice R. Sufrin, Roswell Park Memorial Inst.; Anthony E. Pegg, Hershey Medical Ctr.; Laurence J. Marton, Univ. of California at San Francisco; Robert A Casero (replaced Steve Baylin), Johns Hopkins Univ. School of Medicine; Gordon Luk, Harper Hospital, Detroit, MI

U01 CA51946

08/01/90-07/31/93 		Ralph A. Reisfeld, Ph.D.
Research Institute of Scripps Clinic
La Jolla, CA 		New Tumor Models for the Development of Immunotherapy Stephen D. Gillies, Damon Biotech, Inc.; Barbara M. Muller, Research Institute of Scripps Clinic

U01 CA40884

07/01/85-06/30/90 		Warren Ross, M.D.
University of Florida
Gainesville, FL 		Topoisomerases as New Therapeutic Targets Leroy F. Liu, Johns Hopkins Univ.; Robert Hertzberg, Randall Johnson, Smith, Kline & French Labs.; Timothy MacDonald, Univ. of Virginia

U01 CA57723

08/21/92-07/31/96 		Sydney E. Salmon, M.D.
Univ. of Arizona College of Medicine
Tucson, AZ 		Discovery of Peptide Anticancer Drugs Michal Lebl, The Selectide Corp.; Axel Ullrich, Max-Planck Inst.; Kit S. Lam, Arizona Cancer Ctr.; Joseph Schlessinger, New York Univ.; Victor Hruby, Univ. of Arizona

U19 CA67861

09/08/95-08/31/00 		Michael I. Sherman, Ph.D.
PharmaGenics, Inc.
Allendale, NJ
(replaced by: Katherine Klinger, Genzyme Corp., Framingham, MA) 		Discovery of Natural Products that Restore p53 Function Michael Moore, Xenova Ltd.; Arthur Bertelsen, PharmaGenics, Inc.; Nikola Pavletich, Memorial Sloan-Kettering Cancer Ctr.

U01 CA51958

06/01/90-05/31/93 		Zenon Steplewski, M.D., Ph.D.
The Wistar Institute
Philadelphia, PA 		Radioisotope-Antibody Conjugates for Cancer Therapy Peter Curtis, The Wistar Inst.; Leonard F. Mausner, James F. Hainfeld, Brookhaven National Laboratory

U01 CA60130

08/27/92-07/31/96 		Donald L. Trump, M.D.
University of Pittsburgh
Pittsburgh, PA
(replaced by: Eric Wickstrom
Thomas Jefferson University,
Philadelpha, PA) 		Gene-Specific Therapy of Breast and Pancreatic Cancer Thomas Jefferson Univ.; Barbara Shaw, Duke Univ.; Marvin Caruthers, Univ. of Colorado; J. Dirk Iglehart, Duke Univ.; Rudolph Juliano, Univ. of North Carolina

U19 CA53001

09/30/90-09/29/01 		Frederick A. Valeriote, Ph.D.
Wayne State University School of Medicine
Detroit, MI
(replaced by: Charles Grieshaber, Jerome Horwitz
Wayne State Univ.) 		Discovery of New Anticancer Agents from Natural Products Richard Moore, Univ. of Hawaii; Joseph Hoffmann, Univ. of Arizona; Thomas Corbett, Wayne State Univ., Eli Lilly Corp.

U19 CA67760

09/30/95-09/29/01 		Daniel D. Von Hoff, M.D.
The University of Texas Health Science Center at San Antonio
San Antonio, TX 		Telomere and Telomerase Interactive Agents Shih-Fong Chen, Bradford Windle, Cancer Therapy and Research Ctr.; Laurence Hurley, Univ. of Texas at Austin

U01 CA48405

08/01/88-07/31/91 		Geoffrey Wahl, Ph.D.
The Salk Institute for Biological Studies
San Diego, CA 		Detection and Curing of Amplified Genes in Human Cancer Daniel D. Von Hoff, Univ. of Texas Health Science Ctr. of San Antonio

History of NCDDG RFA Issuances:

Year Issued

Type

Initiative

NIH Guide

1983 Mechanism based NIH-NCI-DCT-DTP 83-6 07/17/83
1984 Mechanism based 84-CA-22 08/03/84
1986 Lung and colorectal cancers 87-CA-01 for lung
87-CA-02 for colon 		10/03/86
10/03/86
1987 Mechanism of action, disease-based, model development 87-CA-24 for disease
87-CA-25 for mechanism
87-CA-26 for models 		08/28/87
08/28/87
08/28/87
1988 Natural products 88-CA-17 09/02/88
1989 Disease-based, mechanism-based and models 89-CA-01 for disease
89-CA-02 for mechanism
89-CA-03 for models 		03/10/89
03/10/89
03/10/89
1991 Mechanism of action and disease-based CA-91-19 08/23/91
1994 Mechanism of action and disease-oriented CA-94-008 06/03/94
1994 Natural products CA-94-007 06/03/94
1995 Mechanism of action and disease-oriented CA-95-020 09/22/95
1999 Mechanism of action and disease-oriented natural products CA-99-010 04/14/99
2004 Mechanism of action and disease and natural products CA-05-001 01/16/04