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(12) Patent Application Publication (10) Pub. No.: US 2004/0092583 A1 Shanahan-Prendergast (43) Pub US 20040092583A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2004/0092583 A1 Shanahan-Prendergast (43) Pub. Date: May 13, 2004 (54) TREATMENT FOR INHIBITING (30) Foreign Application Priority Data NEOPLASTICLESIONS Jan. 2, 2001 (IE)........................................ S2001/0002 (76) Inventor: Elizabeth Shanahan-Prendergast, O O O O County Kildare (IE) Publication Classification Correspondence Address: (51) Int. Cl.7 ..................... A61K 31/343; A.k'S HOFFMANN & BARON, LLP 6900 JERICHO TURNPIKE (52) U.S. Cl. ........................... 514/469; 514/475; 514/762 SYOSSET, NY 11791 (US) (57) ABSTRACT (21) Appl. No.: 10/250,535 The invention discloses the use of incensole and/or furan ogermacrens, derivatives metabolites and precursors thereof in the treatment of neoplasia, particularly resistant neoplasia (22) PCT Filed: Jan. 2, 2002 and immunodysregulatory disorders. These compounds can be administered alone or in combination with conventional chemotherapeutic, anti-rival, anti-parasite agents, radiation (86) PCT No.: PCT/IE02/00001 and/or Surgery. US 2004/0092583 A1 May 13, 2004 TREATMENT FOR INHIBITING NEOPLASTIC 0007 Chemotherapy uses poison drugs that take advan LESIONS tage of cancer cells rapid growth and consumption of large amounts of nutrients. Chemotherapy side effects include 0001. The present invention relates to a method for the nausea and temporary full or partial hair loss. Antimetabo Selective inhibition of neoplastic cells, for example for the lites, one group of these drugs, work by mimicking the treatment, inhibition or prevention of precancerous lesions, nutrients the body's cells consume. Physicians inject these tumours, cancer growth or other neoplasias in mammals. drugs into the bloodstream, where they travel throughout the This invention also relates to the use of the compounds of body, consumed by every cell. Rapidly growing cancerous the present invention including incensole and/or furanoger cells consume much more of the poisonous drugs than do macren, derivatives, metabolites, analogues, mimic mol normal cells. As a result, the drugs destroy cancerous cells ecules and to compositions containing the compounds of the faster than normal cells. Cells reproduce by duplicating their present invention including incensole and/or furanogerma genetic code, or DNA. Another group of chemotherapy cren, derivatives, metabolites, analogues, mimic molecules. drugs interferes with the duplication of DNA, so cells cannot 0002 Cancer develops from changes in the DNA, or reproduce. Chemotherapy drugs act on all the patients genetic material, of the body's cells, causing them to cells-the cancerous cells and the healthy cells. A physi develop into precancerous lesions. Such lesions exhibit a cian's challenge is to administer the drugs to kill only the Strong tendency to develop into malignant tumours, or cancer cells, not the healthy cells. Side effects Such as those cancer. Such lesions include lesions of the breast (that can immediately described prevent the long term or recurrent develop into breast cancer), lesions of the skin (that can use of these drugs. Furthermore, there are an increasing develop into malignant melanoma or basal cell carcinoma), number of effective drugs that can no longer be used due to colonic adenomatous polyps (that can develop into colon resistance by the causative agent. cancer), and other Such neoplasms. 0008 Researchers have refined these three cancer treat 0.003 Cancer may take years to develop. The process ments (Surgery, radiation therapy and chemotherapy) over typically begins with some disruption to the DNA of a cell, the past 20 years. As a result, the Survival rate among cancer the genetic code that directs the life of the cell. Many things, patents has increased dramatically. But, the Success of any Such as diet, tobacco, Sun exposure or certain chemicals can treatment for cancer depends on how much the cancer has cause Such disruptions. Some cells will enter a precancerous Spread before treatment begins. Once cancer metastasises, or phase, known as dysplasia. Some cells will also enter the Spreads into different areas of the body, treating it with State of carcinoma in situ, in which the cancer cells are Surgery, radiation therapy or chemotherapy becomes more restricted to a microScopic Site and do not pose a great threat. difficult. AS the tumour mass increases and cancerous cells Eventually, unless the body's own immune System takes proliferate, the cancer may become resistant to any type of care of the wayward cells either on its own or by being therapy medicine can provide. enhanced by Specific chemicals, a tumour will develop. It 0009 Early cancer detection is critical to successful may take as long as 30 years for a tumour to go through the treatment. If physicians destroy tumours before they have entire proceSS and become large enough to produce clinical had an opportunity to spread, a person with cancer has a Symptoms. much greater chance for Survival. 0004 Anyone can get cancer, including children, but it is 0010. The search for drugs useful for treating and pre most common in people over the age of 50. This year about venting cancer is intensive. Indeed, much of the focus of 1.22 million people in the United States will be diagnosed cancer research today is on the prevention of cancer because with cancer (not including the more than 1 million annual chemotherapy for cancer itself is often not effective and has cases of basal and Squamous-cell skin cancers.) About Severe side effects. Cancer chemoprevention is important for 563,000 people will die of cancer this year. Treatment for recovered cancer patients whom retain a risk of cancer cancer has progressed rapidly over the last 30 years. Doctors recurrence. Also, cancer chemoprevention is important for generally prescribe three main treatments for cancer: Sur individuals who, have not yet had cancer, but have heredi gery, radiation therapy, chemotherapy or a combination of tary factors that place them at risk of developing cancer. these. Choosing a course of medical treatment depends With the development of new genetic Screening technolo largely on the cancer type, Stage of progression, and loca gies, it is easier to identify patients with high-risk genetic tion. actors, whom would greatly benefit from chemopreventative 0005 Surgery is generally advisable when physicians can drugs. Therefore finding Such anti-cancer drugs that can be safely remove the cancer from the body. In situations where used for prolonged preventive use is of Vital interest. the cancerous cells have spread, Surgeons Sometimes must 0011. Unfortunately, most chemotherapeutic drugs have remove large areas of healthy tissue along with the tumour Serious Side effects that prohibit their long-term use, or use to insure that no malignancy remains. In these cases, phy in otherwise healthy individuals with precancerous lesions. Sicians remove lymph nodes from the tumour area because There side effects, which are a result of non-specific toxicity cancer can spread through nodes. However, unfortunately of the drugs, immunosuppression and other toxicities. For most cancers are discovered too late for Surgical cure. In this reason there is a need to identify new drug candidates many cases, the patient does not experience Symptoms until for therapy of patients with precancerous lesions that do not the cancer has progressed to a malignant stage. have Such Serious Side effects in humans. 0006 Radiation therapy is used to destroy cancer cells. 0012. The in vitro anti-tumour activity of several natural Ironically, radiation can cause and destroy cancer. Side products has recently been examined to identify new com effects of radiation therapy include radiation Sickness, which pounds that inhibit the cancer cells whilst having lower Side are nausea and Skin redness in the tumour area. effects, as described in U.S. Pat. No. 580,925; U.S. Pat. No. US 2004/0092583 A1 May 13, 2004 6,051,565, U.S. Pat. No. 6,080,741; U.S. Pat. No. 5,578,637; 0021. In one embodiment, the compounds of the present U.S. Pat. No. 5,578,637; U.S. Pat. No. 5,663,196, U.S. Pat. invention are Selected from the group comprising: No. 5,602,184; U.S. Pat. No. 5,817,816: and U.S. Pat. No. 56,077,840 to list but a few. A new group of drugs, utilizing monoclonal antibodies, designed to affect only cancer cells, Formula (1) leaving healthy cells intact have been tested. U.S. Pat. No. 5,064,823 discloses the anticancer activity of pentacyclic triterpenoid compounds which possess topoisomerase inhibitory activity. U.S. Pat. No. 5,876,728 is directed to a composition for treating cancer that contains at least three Formula (2) herbal extracts. These previously described compounds are unrelated to the present invention. 0013 However, despite these developments, there exists a continuing need for chemotherapeutic agents which inhibit tumour growth, especially Solid tumour growth and which have an adequate therapeutic indeX to be effective for in vivo treatment. 0.014. The correlation between the compounds of the 0022) wherein for Formula (1) present invention, incenSole and furanogermacren, deriva tives, metabolites, analogues and/or mimic molecules and 0023 Bonds between carbons 9-10, 10-1, 1-2, 2-3.3-4, neoplasia was not recognised prior to the work of the 4-5, 5-6, can be either single or double with the proviso that applicant. Accordingly the following provides information any two or more double bonds are separated by a single on each of these topics. bond. 0024 Compounds also include those containing epoxide 0.015 The present invention is directed to a composition rings formed between carbons 9-10, 10-1, 1-2, 2-3.3-4, 4-5 comprising one or more compound of the present invention with the proviso that any two or more epoxide rings are described herein, their derivatives, metabolites, analogues Separated by a Single bond.
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