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Genetic Linkage

Matching Cancer Patients to Targeted Drugs: Two New Tools

A choreography of mutational events drives cancer cells to invade and metastasize, changing the biology in ways that enable the errant cells to resist treatments. While the traditional slash-and-burn approaches of chemotherapy and radiation attack rapidly-dividing cells, targeted treatments zero in on the altered proteins that reflect precise genetic changes in tumor cells. These are the somatic (“body”) mutations in just the affected cells, not the inherited mutations present in all of a patient’s cells.

Two new papers introduce tools to better match patients to targeted treatments or immunotherapies, based on interpreting the mutations behind a cancer’s initiation and spread. One is a machine learning tool called Cerebro, the other a scale for physicians to rank the evidence that a particular targeted treatment will work against a tumor with specific mutations.

To continue reading go to DNA Science Blog at Public Library of Science, where this post first appeared. Read More 
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Poliovirus To Treat Brain Cancer: A Curious Chronology

Certain things have a natural order. Breakfast before lunch. Infancy before adolescence. Autumn before winter.

So I was surprised to read an article last week in Science Translational Medicine about experiments at Duke University treating cancer in human cells and in mice with an engineered poliovirus, when the television news show 60 Minutes had reported on four patients receiving the treatment for brain tumors back in 2015. Doesn’t preclinical work – cells and animal models – come first?

I decided to investigate. Read More 
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Targeting Cancer: A Basketful of Hope

Basket studies allow researchers to evaluate considering a cancer's mutations in choosing treatment. (NHGRI)
Targeted treatments for cancer have been extending and saving lives for more than 15 years — precision medicine isn’t a new idea in oncology. Now drugs pioneered on select, specific cancers are, one by one, finding new applications.

The first wave of targeted drug approvals were for cancers associated with specific mutations. Herceptin (traztuzumab) led the way, approved in 1998. It’s a monoclonal antibody deployed against the HER2/neu receptor that is overabundant in some aggressive and early-onset breast cancers. Robert Bazell’s excellent book Her 2 tells the tale.

In 2001 came the blockbuster Gleevec (imatinib), a small molecule tyrosine kinase inhibitor that intercepts signals to divide. Erin Zammett’s My So-Called Normal Life with Cancer relates that story. A very young editor at Glamour magazine when a routine check-up revealed chronic myelogenous leukemia, Erin’s recovery was one of the first of thousands thanks to this now famous drug. Read More 
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Celebrating Gleevec – and Basic Research

Peter Nowell and David Hungerford began the work that led to the successful cancer drug Gleevec (Penn Medicine)
When 23-year-old Glamour magazine editor Erin Zammett Ruddy went for a routine physical in November 2001, she expected reassurance that her healthy lifestyle had been keeping her well. After all, she felt great. What she got, a few days later, was a shock. Instead of having 4,000 to 10,000 white blood cells per milliliter of blood, she had more than 10 times that number – and many of the cells were cancerous.

Erin had chronic myeloid leukemia (CML). Two years before her diagnosis, CML was a death sentence. But the drug Gleevec saved her and many others. It offers perhaps the best example of translational medicine. Read More 
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Second Gene Causes Retinoblastoma

This little boy has heritable retinoblastoma. The mutation originated in him, so he didn't inherit it, but he can pass it on.
In a list of famous genes, RB1 would probably be #1. It’s the tumor suppressor gene whose “loss of function” is behind the childhood eye cancer retinoblastoma, and that Alfred Knudson investigated to deduce the 2-hit mechanism of cancer.

In 1971, the idea that the normal function of a gene could be to prevent cancer was revolutionary. Now a study in Lancet Oncology finds that an amplified oncogene can cause the eye cancer too, with just one “hit.” Read More 
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4 Suggestions for Halting the Lethality of Cancer

Brain tumors (photo from Glia, 2002, Ignatova, T. et al, courtesy D.A. Steindler.)

(Originally published at Scientific American, guest blog, June 26)

I had a very strange week. While in Washington, D.C., writing news releases for the Model Organisms to Human Biology: Cancer Genetics meeting sponsored by the Genetics Society of America, I had left, back home in upstate New York, my dear hospice patient. Ruth was nearing the end of her battle with liver cancer. It was jarring to go from holding her hand to listening to litanies of deranged signal transduction pathways and cascades of mutations that cause the damn diseases. Read More 
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