Ca 125

As mentioned earlier, CA 125 has shown promise for early detection of ovarian cancer and detection of recurrence. The rate of decline of CA 125 during chemotherapy has also been shown to be a potential prognostic marker. Several reviews have been written on the topic (13,132) and interested readers are referred to these reviews for a detailed discussion.

ERBB2 is a member of the epidermal growth factor receptor family of receptor tyrosine kinases. Activation of this receptor activates downstream signaling pathways, such as those involving mitogen-activated protein kinase, phosphatidylinositol-3 kinase, and angiogenic pathways (133). Amplification and overexpression of ERBB2 is seen in up to a third of ovarian tumors. ERBB2 signaling has been shown to be important in ovarian cancer development. However, ERBB2 overexpression does not appear to be an independent prognostic factor of ovarian cancer patients (72,134-142), although some studies have found that it could independently predict survival in some cases (143-145). Experiments have demonstrated that ERBB2 expression does not appear to affect the response to conventional, cytotoxic therapy

(146). However, because a significant proportion of ovarian cancers expresses this protein, therapeutic strategies aimed at inhibiting this receptor, represent a promising approach and may reverse the malignancy induced by HER2/Neu overexpression

(147). The monoclonal antibodies Herceptin and Iressa, for example, are currently being investigated for this purpose.

3.5. Kallikreins

Kallikreins have been found overexpressed or underexpressed in various cancers (19). The early investigations of kallikreins in ovarian cancer have been extremely promising. Indeed, multiple kallikreins (hK4-15) have been shown to be independent prognostic factors in ovarian cancer (20,21,148-162). The results are summarized in Table 2. The expression of certain kallikreins, such as hK8, hK9, hK11, hK13, and hK14, was associated with favorable prognosis (149,151-153,160-162), whereas others, such as hK4, hK5, hK6, hK10, and hK15 were associated with poor prognosis (20,21,148,154,156-159). Interestingly, hK4 expression has been associated with taxol resistance (155). It will be important to continue investigating these very promising markers to determine whether they can be useful in the clinic.

3.6. Gene-Expression Patterns

As the processes important in tumor initiation, progression, and development of drug resistance have been shown to be multifactorial and involve multiple molecular pathways, it is likely that overall gene-expression profiles will represent a powerful tool for identifying subset of tumors with particular behavior. For example, several studies performed in the last 4 or 5 years have demonstrated the power of microarrays

Table 2

Prognostic Value of Kallikreins

Table 2

Prognostic Value of Kallikreins

Protein

Detection method

Prognosis

Univariate

Multivariate

Reference

hK4

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