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tumor, have the worst prognosis. Molecular tests for TP53 and RER are already
considered to offer prognostic value in certain types of cancer. In addition, the abil-
ity to locate residual cancer by molecular methods can aid in predicting the course
of the disease.
A more accurate means of prognosis in breast cancer will improve the selection
of patients for adjuvant systemic therapy. Gene signatures seem to be promising for
predicting outcome, and should pave the way for new therapies that are tailored to
the patient. Gene-expression profi les based on microarray analysis can be used to
predict patient survival in early-stage lung adenocarcinomas. The identifi cation of a
set of genes that predict survival in early-stage lung adenocarcinoma allows delin-
eation of a high-risk group that may benefi t from adjuvant therapy. Differentially
expressed genes were used to generate a 186-gene “invasiveness” gene signature
(IGS), which is strongly associated with metastasis-free survival and overall sur-
vival for four different types of tumors: breast cancer, medulloblastoma, lung can-
cer, and prostate cancer (Liu et al. 2007 ). The prognostic power of the IGS was
increased when combined with the wound-response signature based on transcrip-
tional response of normal fi broblasts to reveal links between wound healing and
cancer progression.
Detection of Mutations for Risk Assessment and Prevention
Tests with the greatest potential for risk assessment include those that target muta-
tions in the following genes:
- BRCA1 and BRCA2 (for breast and ovarian cancers);
- MLH1 and MSH2 (colon cancer);
- APC (for familial adenomatous polyposis);
- RET (for medullary thyroid cancer);
- TP53 (for several tumors);
- CDKN2A (for melanoma);
- RB1 (for retinoblastoma).
Detection of mutation in an individual would theoretically lead to increased sur-
veillance. Lifestyle changes might be advised to avoid known risk factors for pro-
gression of cancer. In some cases, prophylactic surgery may be recommended. In
addition, some chemotherapeutic agents might be prescribed on a preventive basis.
Detection of a mutation may be followed by surveillance-oriented examinations,
including those involving colonoscopy, mammography, measurement of prostate-
specifi c antigen, and other tests. This tactic will promote the early detection of can-
cer and early management. Current molecular research is expected to reveal other
markers for early diagnosis of cancer. In addition, the possibility of generating
genetic profi les for individual tumors offers unique opportunities for distinguishing
between metastases and primary tumors.
10 Personalized Therapy of Cancer