About This Project

Ask the Scientists

What is the context of this research?

• Malignant cancer is such a life threatening disease in part because the original tumor sheds cells which migrate to other tissues in the body, a process called metastasis. Thus cancer cells originating in the breast or prostate can spread to vital organs like the liver, brain or bone.
• Chemotherapy currently uses highly toxic chemicals to kill rapidly dividing cancer cells, but often it's a race against time to find a chemo drug to which the cancer isn't genetically resistant. Metastatic cells also generally resist other treatments like radiation.
• Modern cancer drugs are very sophisticated in being able to target a specific subtype of one variety of cancer. But this complexity makes cancer treatments expensive. Our drug could be used broadly as an initial frontline and cost-effective therapy.

What is the significance of this project?

Dr. Montano's lab studies a gene HEXIM1, which acts as a master control switch. Cells which have low levels of HEXIM1 divide rapidly, are likely to be cancerous and spread readily. Cells which are high in HEXIM1 are unable to divide or spread and are termed "differentiated". Typically differentiated cells form tissues and organs.

There are known chemicals called differentiating agents and some of these can increase the levels of HEXIM1 inside cells. One of these, HMBA, would be a useful chemotherapeutic drug, but has low potency and moderate toxicity. Dr. Montano and her collaborator Dr. Bin Su have made new HMBA-derived inducers of HEXIM1 with higher potency/lower toxicity for the treatment of multiple cancers including solid tumors such as those found in breast, prostate, lung etc.

What are the goals of the project?

Previously, we experimentally turned up (induced) HEXIM1 in mice either by genetic engineering or by administering the drug HMBA. We were able to inhibit the spread of breast cancer to the lungs in these mice, which are bred to have a highly aggressive form of breast cancer. Previous experiments with cultured breast cancer cells tell us which of the new HMBA derivatives induce HEXIM1 and are most likely to have high potency and low toxicity.

1. Breed a new cohort of mice for the experiment so that we have meaningful numbers of test animals.
2. Effective doses of the test drugs will be administered to the mice and the progress of disease followed under University approved ethical protocols.
3. At the end of the study lungs will be examined for metastases and breast tumors for metastatic cells.