• 5/30/2008
  • San Francisco, CA
  • Jeffrey Norris
  • UCSFToday (pubaffairs.ucsf.edu/today)

A new chapter in the saga of the war on cancer is being written. The subject is cancer stem cells. If more patients are to survive, then these cells must die. But many targeted treatments might be missing them.

Communication between cancer experts and stem cell experts is at an exciting, pioneering stage. An important moment in the evolution of this convergence happened last Thursday and Friday at the UCSF Mission Bay campus – a “Stem Cells and Cancer” symposium presented by the UCSF Helen Diller Family Comprehensive Cancer Center, in association with the UCSF Institute for Regeneration Medicine. The symposium brought together research leaders from around the world.

Clearly, cancers sometimes grow back even after treatment appears to have eliminated any trace of disease. But only in recent years has a critical mass of researchers begun to explore the roles of cells within cancers that appear to be stem cells, or that act like stem cells.

Forever Young, and Sometimes Deadly

Stem cells are eternally youthful, immature cells that have infinite capacity to spin off new cells. In this way, they maintain and repair tissue. In contrast, their progeny cells normally mature and grow old. The progeny assume specialized tasks, and they have little or no capability to regenerate themselves. The persistence of abnormal cancer stem cells may be the key to why many cancers come back and resist further treatment.

Most experts believe these cancer stem cells represent a very small fraction of the tumor mass. Nonetheless, a few cancer stem cells are able to re-create an entirely new tumor. By contrast, in many cases, the cancer cells that make up the bulk of the tumor are not capable of sustaining tumor growth.

It is becoming clear that treatment which targets the bulk of the tumor cells may miss some or all of these cancer stem cells. The cancer stem cells are then able to reseed the tumor. This regrowth of the cancer might not become apparent for months or years.

Researchers are already exploring treatments that specifically target cancer cells in the tissue where they are best understood – the cells of the immune system – but the first human trials have not yet begun.

Cancer stem cells share many properties with normal stem cells. Normal stem cells give rise to tissues during embryonic development, and maintain and repair tissues throughout a lifetime. It is important to study both normal and cancer stem cells, and their similarities and differences. Symposium speakers presented research on both.

The molecular fingerprints of cancer stem cells have not been precisely identified. As it stands, a tumor that can regenerate when transplanted into a mouse is regarded as a cancer stem cell. Researchers are busy sorting and describing these cells.

One of the symposium’s organizers, UCSF cancer stem cell researcher Emmanuelle Passegué, PhD, suggests that one of the earliest applications in the clinic of cancer stem cell research is likely to be the development of tests that reveal cancer stem cell prevalence, location and spread within cancer patients. Such data can provide prognostic information that can be used to weigh treatment options.

The Same Cancer Gene Acts Differently in Different Cell Types

Normal genes that go bad, called oncogenes, were shown by UCSF researchers in the 1970s to be the trigger that helps turn normal cells into cancerous cells. But in the development of cancer, the type of cell in which an oncogene becomes activated also matters.

“The consequences of the activation of a cancer gene are different in stem cells than in mature cells,” Passegué explains. Nobody fully understands these differences very well yet – but they are the focus of very active research.

Passegué’s own area of expertise is the study of cancer stem cells in leukemia, a field that really got going about a decade ago. Only in the past few years, she says, have researchers begun to identify cancer stem cells in other, solid tumors – such as colon cancer, head and neck cancer, prostate cancer, brain cancer, and the deadly skin cancer called melanoma.

“In terms of developing something that kills the cancer stem cells, eradicating the disease and leaving normal stem cells untouched, there is still plenty of work to do,” Passegué says. The first treatments are likely to be developed for leukemias, she adds.

The symposium was sponsored in part by a UC Discovery Grant. Corporate sponsors provided additional support. Symposium planners were UCSF cancer experts Martin McMahan, PhD, and Gabrielle Bergers, PhD, along with Passegué.