Heineken Lectures 2004

The Dr. A.H. Heineken Prize for Medicine

Blackburn, Elizabeth H.

2005 | ISBN 90-6984-434-6 | gratis

Heineken Lecture by Professor Elizabeth H. Blackburn, winner of The Dr A.H. Heineken Prize for Medicine 2004.

Telomeres protect and stabilize the ends of chromosomes. They consist of simple DNA sequences, tandemly repeated at the ends of chromosomes, which bind protein factors and make a 'cap', thus securing each end of every chromosome. Without telomeric DNA and its special way of replicating, chromosome ends dwindle away. We have explored molecular features of the telomerase ribonucleoprotein that are needed for its capability to maintain telomeres and keep cells dividing. Loss of telomere function promotes cancer and may occur in human aging. Telomerase plays key roles in cancer in two ways. First, lack of adequate telomerase can lead to loss of telomere functions that may promote early stages of development of cancer, and occur in human aging. A second aspect of cancer, long known to be central to cancer maintenance, is that late-stage cancer cells are effectively immortal and resistant to cell death. Indeed, as most cancers progress, telomerase activity becomes strongly active. Our new results unexpectedly and further implicate telomerase in cancer progression, showing that telomerase promotes metastasis of cancer as well as cancer cell proliferation. We have focused on exploiting the high telomerase activity frequently seen in cancer cells.

To explore new strategies for treatment of cancer that can be translated into rational cancer therapies, using a variety of human cancer cell types, we have shown that we can block tumor cell growth by altering the action of telomerase in two different ways, each eliciting distinct cellular responses. Our recent work and progress to date on targeting telomeres and telomerase will be described.