Research at Cornell: Why is testicular cancer is so easy to treat with chemotherapy?

Advances in chemotherapy have become an important method of cancer treatment, but many cancers still have a poor prognosis and do not respond well to chemotherapy. One type of cancer which has shown astonishing levels of response to chemotherapy is testicular cancer: in 1970, only 5% of patients with highly advanced testicular germ cell tumors survived to the 5 year mark; this number increased to 74% by the early 2000’s, a survival rate which remains considerably higher than other advanced solid cancers. This improvement has been attributed to the sensitivity of testicular germ cell cancer cells to chemotherapy. The million-dollar question remains: why this treatment is so effective in testicular cancer, and not in other types of cancer?

Tim Pierpont, a graduate student in Robert Weiss’ lab at Cornell, believes that the answer may lie in the unique properties inherited from the cells that gave rise to the tumor. Most testicular cancers arise from the germ cells (the precursors to sperm, or an egg in females), and the few that arise from other parts of the organ (5%) have much poorer outcomes. The unique properties of the germ cells may thus explain why these tumor cells are much more sensitive to the effects of chemotherapy.

Tim is studying the mechanism of DNA damage response in these cancerous germ cells. Because germ cells are the cells that eventually give rise to an embryo, any DNA damage, or mistakes made during DNA damage repair, could be passed on to the next generation with devastating results. Germ cells are thus much more likely than other cells to die if DNA damage is detected. Chemotherapy drugs that work by causing DNA damage are thus extremely effective in eradicating testicular germ cell cancer cells.

Tim’s results will help explain why testicular cancer is so easy to attack with chemotherapy, and hopefully offer clues on how to make other tumors similarly sensitive to chemotherapy.

Many thanks to Tim Pierpont who sat down with me to talk about his research and elucidated many aspects of DNA damage!

Cancer stem cells

Image credit: http://www.verastem.com/research/

The latest buzzword (or, rather, words) in the cancer research world is “cancer stem cells”. These stem cells are thought to exist in tumours, and the theory goes that they are the reason that many cancers reoccur and medications fail. But what are these stem cells really, and how are they going to help us understand and fight cancer?

Stem cells are, by definition, cells that are capable of self-renewal (when they divide at least one of the two cells remains a stem cell), and are capable of transforming into other cell types. We have small reserves of stem cells in our body, for example in the bone marrow we have stem cells that produce blood, or in the muscle we have stem cells that form new muscle fibers when we exercise or damage our muscles.

In cancer, it has been proposed that a similar small reservoir of cancer stem cells exists within the tumour, and  these cells are not always capable of being targeted by chemotherapies. Thus, drugs may cause the tumour to shrink, but cancer stem cells may still remain and produce new tumor cells. Furthermore, if these stem cells which survive, pick up a new mutation that renders them immune to the chemotherapy, the tumour becomes chemotheraphy-resistant and continues to grow. Therefore, the answer does not only lie in finding drugs that can attack tumors and reduce their size, but in also finding a way to attack a potential source of the tumour: cancer stem cells. Similar to a video game, you don’t win by attacking the little guys, you win by attacking the big guy at the end of the game.

Because stem cells could be the key to unlocking the secrets of fighting cancer, extensive research is now going into understanding and fighting cancer stem cells. Researchers are beginning to further understand the mechanisms that allow  cancer stem cells to be resistant to chemotherapy. These resistant properties, which differ from normal cells, may even be used to develop targets for future drugs aimed at cancer stem cells.

Many thanks to Tim Pierpont for suggesting the topic of this blog post and providing additional information! For a short video on cancer stem cells made by the Canadian Stem Cell Foundation, visit this link.