303et al. 2011 ). Breast cancer treatment sensitivity was predicted using combination of
signatures for (1) sensitivity to endocrine therapy, (2) chemoresistance, and (3) che-
mosensitivity, with independent validation and comparison with other reported
genomic predictors of chemotherapy response. A genomic predictor combining ER
status, predicted chemoresistance, chemosensitivity, and endocrine sensitivity and
identifi ed patients with high probability of survival following taxane and anthracy-
cline chemotherapy.
Use of PET to Determine Response to Chemotherapy In patients with meta-
static breast cancer, sequential 18F-FDG PET enables prediction of response to
treatment after the fi rst cycle of chemotherapy. The use of 18F-FDG PET as a sur-
rogate endpoint for monitoring therapy response offers improved patient care by
individualizing treatment and avoiding ineffective chemotherapy.
Prediction of Response to Paclitaxel Breast cancers show variable sensitivity to
paclitaxel. Tubulin polymerization assay has been used to show that low tau expres-
sion renders microtubules more vulnerable to paclitaxel and makes breast cancer
cells hypersensitive to this drug. Low tau expression, therefore, may be used as a
biomarker to select patients for paclitaxel therapy. Inhibition of tau function by
RNAi might be exploited as a therapeutic strategy to increase sensitivity to
paclitaxel.
Predicting the Response to Anti-estrogen Drugs According to the NCI, about
two-thirds of women with breast cancer have estrogen receptor (ER)-positive breast
cancer, in which tumor growth is regulated by the natural female hormone estrogen.
Estrogen is known to promote the growth of most types of breast cancer. However,
another gene, the retinoblastoma tumor suppressor (RB) gene, is functionally inac-
tivated in the majority of human cancers and is aberrant in one-third of all breast
cancers. RB regulates G1/S-phase cell-cycle progression and is a critical mediator
of antiproliferative signaling. RB defi ciency compromises the short-term cell-cycle
inhibition following cisplatin, ionizing radiation, and anti-estrogen therapy of breast
cancer with drugs such as tamoxifen (Bosco et al. 2007 ). Specifi c analyses of an RB
gene expression signature in human patients indicate that deregulation of this path-
way is associated with early recurrence following tamoxifen monotherapy. Thus,
because the RB pathway is a critical determinant of tumorigenic proliferation and
differential therapeutic response, it may represent a critical basis for directing ther-
apy in the treatment of breast cancer. The RB tumor suppressor can be used as a
biomarker for how tumors will respond to anti-estrogen therapy and could become
the basis for deciding how patients with ER-positive breast cancer are treated clini-
cally. This is a way to predict when anti-estrogen drug therapies are inappropriate
for patients with hormone-dependent breast cancer so that physicians can immedi-
ately begin treating the patient with alternative drugs that are more likely to suc-
ceed. However, comprehensive clinical research is needed before this new method
for predicting the success of anti-estrogen drugs is applied in daily patient care.
Role of p63/p73 Pathway in Chemosensitivity to Cisplatin Breast cancers lack-
ing estrogen and progesterone receptor expression and Her2 amplifi cation exhibit
Personalized Management of Cancers of Various Organs