Office of Technology Development

Combinations of PKC Inhibitors and Therapeutic Agents for Treatment of Cancer

SK 684

Summary of Invention

Protein kinase C (PKC) plays a role in carcinogenesis, tumor cell metastasis, and cell apoptosis. Researchers at Memorial Sloan-Kettering have discovered that specific inhibitors of PKC, in combination with cytotoxic agents, may prove useful in cancer therapy by potentiating apoptosis in tumor cells.

Based on promising in vitro and in vivo studies, two Phase I clinical trials of paclitaxel and PKC inhibitor therapy (using either flavopiridol or bryostatin) are ongoing at Memorial Sloan-Kettering Cancer Center in patients with various solid tumors. Notably, the combination therapies are especially active against esophageal and prostate cancers.

Through the studies, MSKCC scientists have discovered that the specific order and dosage of the PKC inhibitors and the chemotherapeutic agent are essential for clinical enhancement of tumor cell apoptosis. Based on their successes, the researchers have designed a screen for new PKC inhibitors that may prove useful in potentiating apoptosis in tumor cells and in identifying the proper sequence of administration of drugs.

Advantages

Potentially large market for various solid tumors.
The combination therapy has been shown to be superior to chemotherapeutic single agents in inducing apoptosis in several tumor cell lines with a variety of PKC inhibitors.
Patients who have failed to respond to Flavo and Taxol as single agents have responded to combination therapy.

Areas of Application

Screening and therapeutic tool

Stage of Development

Clinical studies in progress (e.g., flavopiridol plus paclitaxel combination study)

Lead Inventor

Gary K. Schwartz, MD

Patent Information

U.S. patents issued:

Licensing strategy

Field of use

Contact Information

Lisa Placanica, PhD
Tel: 212-639-6181, Fax: 212-717-3439
E-mail: placanil@mskcc.org

Categories

Therapeutics

administration (ad-MIH-nih-STRAY-shun)

In medicine, the act of giving a treatment, such as a drug, to a patient. It can also refer to the way it is given, the dose, or how often it is given.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

apoptosis (A-pop-TOH-sis)

A type of cell death in which a series of molecular steps in a cell leads to its death. This is the body’s normal way of getting rid of unneeded or abnormal cells. The process of apoptosis may be blocked in cancer cells. Also called programmed cell death.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

cancer (KAN-ser)

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

carcinogenesis (KAR-sih-noh-JEH-neh-sis)

The process by which normal cells are transformed into cancer cells.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

cell (sel)

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

chemotherapeutic agent (KEE-moh-THAYR-uh-PYOO-tik AY-jent)

A drug used to treat cancer.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

clinical (KLIH-nih-kul)

Having to do with the examination and treatment of patients.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

combination therapy (KOM-bih-NAY-shun THAYR-uh-pee)

Therapy that combines more than one method of treatment. Also called multimodality therapy and multimodality treatment.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

cytotoxic (SY-toh-TOK-sik)

Cell-killing.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

esophageal (ee-SAH-fuh-JEE-ul)

Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

flavopiridol (FLAH-voh-PIH-rih-dol)

A substance being studied in the treatment of several types of cancer. It stops cells from dividing and may kill cancer cells. It is a type of cyclin-dependent kinase (CDK) inhibitor. Also called alvocidib and HMR 1275.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

kinase (KY-nays)

A type of enzyme that causes other molecules in the cell to become active. Some kinases work by adding chemicals called phosphates to other molecules, such as sugars or proteins. Kinases are a part of many cell processes. Some cancer treatments target certain kinases that are linked to cancer.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

metastasis (meh-TAS-tuh-sis)

The spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a “metastatic tumor” or a “metastasis.” The metastatic tumor contains cells that are like those in the original (primary) tumor. The plural form of metastasis is metastases (meh-TAS-tuh-SEEZ).

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

paclitaxel (PA-klih-TAK-sil)

A drug used to treat breast cancer, ovarian cancer, and AIDS-related Kaposi sarcoma. It is also used together with another drug to treat non-small cell lung cancer. Paclitaxel is also being studied in the treatment of other types of cancer. It blocks cell growth by stopping cell division and may kill cancer cells. It is a type of antimitotic agent. Also called Taxol.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

PKC

An enzyme found throughout the body's tissues and organs. Several forms of PKC are involved in many cellular functions. PKC is being studied in the treatment of cancer. Also called protein kinase C.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

prostate (PROS-tayt)

A gland in the male reproductive system. The prostate surrounds the part of the urethra (the tube that empties the bladder) just below the bladder, and produces a fluid that forms part of the semen.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

protein (PROH-teen)

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

screening (SKREE-ning)

Checking for disease when there are no symptoms. Since screening may find diseases at an early stage, there may be a better chance of curing the disease. Examples of cancer screening tests are the mammogram (breast), colonoscopy (colon), and the Pap test and HPV test (cervix). Screening can also include checking for a person’s risk of developing an inherited disease by doing a genetic test.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

Taxol (TAK-sol)

A drug used to treat breast cancer, ovarian cancer, and AIDS-related Kaposi sarcoma. It is also used together with another drug to treat non-small cell lung cancer. Taxol is also being studied in the treatment of other types of cancer. It blocks cell growth by stopping cell division and may kill cancer cells. It is a type of antimitotic agent. Also called paclitaxel.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

therapeutic (THAYR-uh-PYOO-tik)

Having to do with treating disease and helping healing take place.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

therapy (THAYR-uh-pee)

Treatment.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

tumor (TOO-mer)

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)