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radiation. Screening blood for the activity level of 24 genes can identify those
patients most likely to react badly to radiation (Rieger et al. 2004 ). This tool may
help physicians to tailor treatments for individual patients. Some factors are a tip-
off that a patient may have an unusually severe reaction to radiation. Patients who
have autoimmune diseases such as diabetes or lupus, or who have certain rare
genetic diseases need to be monitored carefully or avoid radiation altogether. Even
beyond these obvious signs, some patients suffer disfi guring, disabling or extremely
painful effects. These may include wounds that do not heal, skin burns so severe
they require plastic surgery, or brain damage. Past attempts to identify these patients
by screening the cancer cells themselves have failed. Screening blood rather than
cancer cells means the test would be more accessible to patients. Patients who
respond poorly to radiation might have cells that do not properly recognize or
repair radiation- induced DNA damage. These cells may turn on different genes, or
the same genes at different levels, compared with normal cells exposed to radia-
tion. Knowing which patients may have severe radiation toxicity could make treat-
ment decisions easier. For cancers of the breast or prostate, surgical options can be
as effective as radiation. For other cancer patients, radiation may be the best treat-
ment. However, patients at risk for high toxicity may also have cancers that die in
response to much lower radiation doses. In such cases, radiation – though at greatly
reduced doses – may still be an option. Even those patients who do not have severe
radiation toxicity may also benefi t from this study. If you eliminate those patients
with toxicity are excluded, the remaining patients may be eligible for higher doses.
If patients are treated individually rather than as averages, many could receive
higher, more effective doses. Before personalized radiation treatment becomes
possible, investigators must validate the 24-gene test on a larger number of patients.
Then the screen needs to be commercialized to make it available to medical
laboratories.
Genetic profi les of tumor response to treatment techniques available could help
physicians prescribe radiation therapy customized for individual cancer patients’
needs. An important fi nding is that a trio of proteins often present in cancer
cells − NK-κB, extracellular-signal regulated kinase (ERK) and GADD45β − protect
the tumor from destruction by radiotherapy and might lead to radioresistance. These
proteins are co-activated by ionizing radiation in a pattern of mutually dependence
to increase cell survival and defend cells against the cytotoxicity induced by ioniz-
ing radiation. Administration of drugs that block the proteins would enable irradia-
tion of the cancer with lower radiation doses. This would not only be more effective
against the cancer but also less harmful to the patient. A deeper understanding of the
relationship among these protein molecules, gained through genetic testing, would
be the key to a successful attack on cancer. If one can test cancer cells not for just
three proteins but for thousands, the ‘genetic fi ngerprint’ such a test would provide
might help the formulation of better therapies to destroy cancer.
10 Personalized Therapy of Cancer