Theories of Cancer

Check out this thought-provoking piece in the Times of London Literary Supplement yesterday by bladder cancer survivor Sandra Steingraber, reviewing two new books on the intricacies of the scientific, medical and public policy debates about (or rather, the struggles over) how to think about the origins of cancer [links added].

One advantage of being a long-time cancer survivor – besides the obvious – is that it provides a front-row seat in the auditorium of ideas about the disease’s causation. Theories go in and out of fashion over the years, paradigms shift this way and that, and the patient is viewed differently by the medical community depending on which idea is currently on top.
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Two new books expose and explicate the ongoing social contest that is at the heart of our shifting understanding about cancer. They are both important and deserve to be read together. Devra Davis’s book [The Secret History of the War on Cancer] examines the historical forces at work when doubt is cast on the environmental evidence. Phil Brown’s book [Toxic Exposures] explores the opposing social movements that are struggling to rescue this evidence and to bring about public health policy change based on it.

Solving the Adult Leukemia Mystery

When my brother Ed got sick (three years ago this March) we were initially optimistic. The Internet surfing I did in the wee hours after receiving a call from my sister-in-law indicated that his type of leukemia (A.L.L., or 'Acute Lypmphocytic Leukemia') had a very high cure rate (90%).

What we discovered a little later was a chart showing how that broke down by age. Because the vast majority of people who contract ALL are kids, the cure rates reflect their unique physiology and responsiveness to treatment.

The age group with the lowest incidence of A.L.L. is the group that my brother was in (35-39). It is also, we discovered, one of the groups with the lowest cure rate. But because the incidence numbers are so low, the cure rate is almost meaningless statistically.

Opening up my copy of the Dana-Farber magazine recently, I was pleased to see that Ed's lead oncologist Dr. Dan DeAngelo (a real 'rock-star' of a physician and human being -- in all respects) is helping to lead a study into precisely the mystery that killed my brother: why adults die of this thing that the vast majority of kids ultimately survive.

Here's study lead Dr. Stephen E. Sallan:

The early results suggest that cure rates for adults will be much better than in the past, hopefully comparable to those of the older children. Our larger study hopes to build on these results; I believe we are on our way to debunking the asparaginase myth, and hopefully curing more patients.

This much we know: If you are under 21 and you have ALL, you should be on a pediatric-type protocol. All the studies show it is going to double your chances of being alive. What we don't know about is the rest of the population. Is there something fundamentally different about our biological makeup when we're 30 or 40 or 50 that's different from when we're 10 or 20? Is there something different about the leukemia cell? Is there something different about the treatment regimen? Finally, is there something about being a pediatrician or an internist that is fundamentally different in either who we are or how we practice? That's a big mystery, and a key reason why our study covers people up to age 51.

At the end of five years, we hope to have the answers to all of these questions.

This kind of research is important. Won't you help continue it?

Cancer's "Genomic Landscapes"

This morning's issue of the journal Science (released about ten minutes ago) carries a paper ("The Genomic Landscapes of Human Breast and Colorectal Cancers") that I don't claim to even begin to understand... but which sounds tremendously promising. Emphasis added:

Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.

One of the study's authors, Michail Shipitsin, is affiliated with the Department of Medical Oncology at Dana-Farber, as well as the Harvard Medical School. (That's him in the picture above). Go Michail!! Here's another article featuring his work--this one in terms more understandable to us laymen (emphasis added):

Doctors usually measure how well a cancer treatment works by how much tumor it destroys. The more cancer cells killed the better. The eradication of every last mutated cell is ideal, because nearly every tumor cell can regenerate the disease. Or so cancer biologists believed.

Treatments aimed at purported cancer stem cells may miss the deadly metastases that kill patients, suggests a new study...

A radically different idea is transforming cancer research. In this view, a relatively few dangerous cells fuel cancer growth. The implications are profound: find and kill this minority of crucial cells, and the rest of the tumor may languish or even self-destruct. This popular notion is called the cancer stem cell hypothesis.

A new study of human breast cancer tissue challenges this hypothesis in solid tumors. The presence of purported breast cancer stem cells in the primary tumors increased the risk of distant metastases, the researchers found, but the metastases were packed with more differentiated non-stem cancer cells. An experimental molecular therapy that shut down the “stem cells” in culture did not affect the more differentiated cells.

“Patients are killed by the metastases composed of cancer non-stem cells, even though it could have been the cancer stem cells that metastasized,” said senior author Kornelia Polyak, HMS associate professor of medicine at Dana–Farber Cancer Institute. Both groups of cancer cells are bad, she and her co-authors conclude in the March Cancer Cell, with distinct molecular pathways requiring differently targeted drugs.

Go Kornelia!! (That's her, in the picture above.)

Hey, if athletes, actors and musicians can be rock stars, why not cancer researchers too? :)

UPDATE: Turns out Kornelia (Nelly) Polyak was a DFMC teammate in 2006.

Cancer Research Breakthrough - You Ain't Seen Nothin' Yet!

Check out this article on the front page of today's Boston Globe [emphasis added]:

An international team led by a Boston researcher yesterday unveiled the most detailed look ever at the genetic ravages inside a lung tumor, finding at least one target for drug research and laying the foundation for an ambitious - and controversial - federal effort to identify all the DNA damage that causes major cancers...

...the researchers - including scientists from the Dana-Farber Cancer Institute and the Broad Institute of Harvard and the Massachusetts Institute of Technology - said their study validates a new approach to fighting the nation's number two killer: systematically identifying genetic changes that turn healthy cells cancerous, in hopes of finding cancer's weaknesses. The study serves as a pilot project for the federal government's proposed 10-year, $1.5 billion research program to map the genetic blueprint of the 50 most lethal cancers.

"You ain't seen nothin' yet," said Dr. Matthew Meyerson of Dana-Farber and the Broad who is the lead author of the paper posted online yesterday by the science journal Nature. "The potential for finding things that will help cancer patients is so great. This absolutely gives me much more confidence that we should go forward" with similar research in other types of cancer.

Writes DFMC program head, Jan Ross: "Dr. Meyerson, is a Dana-Farber scientist and former Barr Investigator whose early research efforts in this area were funded by DFMC." Those of you who have contributed to DFMC in the past should take a moment to smile with great hope.

Want to fund the next Meyerson? Go here.