How Cancer Therapies Kill Tumour Cells

Sept 2003: A team of Melbourne medical researchers, including Andreas Strasser, Andreas Villunger, Ewa Michalak Leigh Coultas and Jerry Adams have won a two-year worldwide race to find out how cancer cells are killed by certain therapies.

Team leader, Dr Andreas Strasser from the Walter and Eliza Hall Institute, says, “Up to now, we knew that radiotherapy and chemotherapy could kill some tumour cells but not others, and that they could also damage normal tissues - but we did not know how these therapies killed cancer cells.

“ Now, we have demonstrated that one pathway is critical for cancer treatment-induced cell killing. It works like this: imagine that we have a bow and arrow and cancer cells are the target. Radiotherapy and chemotherapy are the strong hand that allows you to get a grip on the arrow. The bowstring is a protein called p53. The arrow itself, which cannot work without the p53 bowstring, is made up of a pair of killer proteins called Puma and Noxa. When the arrow is released from the p53 bowstring, the Puma and Noxa arrow hits the cancer cell target.

“ The problem is, only about half of all human cancers have the p53 bowstring intact, so the radiotherapy and chemotherapy hand has nothing to grip on to. And if there is no p53 bowstring, then the Puma and Noxa arrow cannot be shot at the cancer target. That is a major reason why therapies vary in effectiveness between different types of cancers.

“ This discovery about how the cancer cell killing process works leads us on to the next challenge: to find a drug that will propel the Puma and Noxa arrow directly, bypassing the p53 bowstring that is so often missing. You could say that the challenge will be in trying to remake the Puma and Noxa arrow into a javelin, with no bowstring required to propel the weapon to the cancer cell target.

“ Several other research groups in Europe, the United States and Japan have been racing to solve the same problem as us, which is basically: how does the p53 protein induce cell death? Our Australian team has managed to cross the line first. It feels like winning the Olympic Games marathon by a hair’s breadth.”

Dr Strasser and his team made their discovery by examining genetically modified (or gene “knockout”) mice created in the laboratory.

The research appears in the 18 September 2003 electronic version of Science Express and will appear in hard copy in the next issue of the prestigious journal Science.