Chapter Three

S Scott Armstrong and Lew Silverman recounted to me their initial meetings with Mario and his parents, I could not help but reflect on my own first experiences in treating patients with childhood leukemia. When I was a new clinical associate at the National Cancer Institute (NCI) in Bethesda, Maryland, in 1956, I did not expect to save a single child or adult with any kind of widespread cancer at all. Though Mario's unusual type of leukemia still presents a difficult problem, the care of most...

Glossary

4G10 A monoclonal antibody that detects phosphotyrosine and hence an activated tyrosine kinase. 5-fluorouracil An anticancer drug that inhibits DNA repair and synthesis and thereby reduces the growth of cancer cells. 6-mercaptopurine An anticancer drug that inhibits DNA repair and synthesis, thus reducing the growth of cancer cells, particularly leukemic cells. It is also used as an immunosuppressive agent. Abelson virus or Abelson murine leukemia virus (Ab-MLV) A retrovirus that triggers a...

Info

A very well-written and thoughtful treatise. Gunsalus CK, et al. Mission creep in the IRB world. Science 2006 312 1441. A plea to reduce the scope of IRBs. Hahn WC, et al. Creation of human tumour cells with defined genetic elements. Nature 1999 400 464-8. All three Hahn articles review the work of Hahn and Weinberg on the relatively small complement of genes required to initiate and maintain cancer despite widespread chromosome damage. Hahn WC, Weinberg RA. Modelling the molecular circuitry of...

The Risk of Chemotherapy Resistance

When Flavia and Walter agreed to the two-year course of chemotherapy for Mario, they were relying on the hope that Mario's MLL leukemic cells would not become resistant to the potent combinations of drugs that would be visited on him by Scott Armstrong, Lew Silverman, and their colleagues. Mario's parents did not want to contemplate that risk closely they asked few questions about the development of resistance. But the risk never left Scott's mind as he began the complex protocol he would...

Chapter

When called by Scott to develop a plan for Mario, Lew Silverman was already certain that Mario's leukemia would present a major clinical challenge. The cancer was not the ordinary ALL of childhood. Silverman was confident that detailed laboratory studies would show that Mario had the mixed-lineage leukemia (MLL) of infancy, even though he was older than most of the patients diagnosed with that perilous, rare disorder. Scott had not seen much MLL, which comprises only about 10 percent of all...

Bibliography

Below is an alphabetized list of references that I have used in the preparation of this book. Though the list is largely drawn from medical literature, important newspaper and magazine articles are also included. Precise reference numbers are not employed to avoid the dryness of a textbook. Readers should understand that books must finally be printed and that the publication process, like the gestation of a baby, takes time. The references included here are as of late August 2006. Inevitably...

The Surgical Plan

Modern medical center is a maze of specialties, and even a cancer center can be likened to a rabbit warren. Every professional in a cancer center is committed to the diagnosis, treatment, and prevention of cancer and to further understanding of cancer biology. This creates a source of potential confusion for patients who need to see more than one type of specialist to complete their treatment. The Women's Cancers Program is a perfect example of a well-intentioned but potentially confusing...

The Search for More Smart Drugs

Since the early 1980s when Robert Weinberg and Philip Leder described the importance of myc and ras in cancer, pharmaceutical companies have been busy trying to create drugs that might block the function or the production of oncoproteins and the growth-signaling circuits they activate. Drugs that inhibit myc are technically difficult to design, and progress has been slow. Ras sits in a very strategic position in cells. It is activated by signals that originate on the cell membrane, and it...