Artifical LDL: a new method for treatment of cancer

• Grant number: 95/00591-9
• Support Opportunities: Research Projects - Thematic Grants
• Start date: December 01, 1995
• End date: November 30, 1998
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Raul Cavalcante Maranhao
• Grantee: Raul Cavalcante Maranhao
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant(s): 96/04670-3 - Microemulsions that bind to ldl receptors (lde) as vehicles for anticancer drugs: a phase i/phaseii study of the complex lde carmustine in multiple myeloma patients., AR.EXT

Abstract

To aim chemotherapic drugs specifically at the neoplasmic cells, avoiding the normal tissues has for a long time been the great ideal of cancer treatment, until now yet to be achieved. Maranhão and colleagues (Lipids, 1993) demonstrated that a microemulsion (LDE) similar to lipoprotein of low density (LDE), is capable of incorporating apolipoprotein E, in contact with the plasma, binding itself to the receptors that withdraw LDL from circulation. In acute myeloid leukemia (Cancer Research, 1994) and in mammary carcinoma, neoplasmic strains which display a marked increase in the expression of receptors of the LDL (increase up to 100 times), showed that the LDE concentrates itself in the tumoral tissue, being able to serve as carrier of chemotherapics. Subsequent experiments showed that when a chemotherapic (hydrophobic or lipophilic in nature) is incorporate din the LDE, its capacity to destroy the neoplasmic cell continues intact, possibly even increased. In experiment begun 45 days ago, the authors are treating a carrier of metastatic pancreatic carcinoma with the chemotherapic carmustin (BCNU) associated with LDE, observing that the collateral effects of the drug were totally abolished. The aim of the present project is to make viable the effective application of the LDE method in the routine treatment of cancer, in those various lines which manifest the increase in the LDL receptors )(such as acute myeloid leukemia, multiple myeloma, carcinoma of the lung, prostate, uterus, breast, the biliary tract, among others). In seven different sets of experiments, it is proposed to study the incorporation to LDE of various lipophilic chemotherapics, proceed to toxicity studies in animals, study in cell cultures the effect of cell destruction of various drugs, to focus the incorporation of multiple drugs into LDE, verify the tropism of LDE through various lines of neoplasmic cells, to study the diagnostic possibilities of the method and, finally, and most important, treat patients carrying four types of cancer: of the breast, of the pancreas, multiple myeloma and acute myeloid leukemia, with a view to observing both the collateral effects of the LDE-chemiotherapic complex as well as the antineoplasmic action. Brought to a successful conclusion, which means minimizing the devastating effects of chemotherapy and increasing its efficiency, this project could give rise to a true revolution in the treatment of cancer. (AU)