pAkt at Ser473 Predicts Benefit of Paclitaxel Therapy in Breast Cancer

Akt is a serine/threonine protein kinase that has been implicated in the pathogenesis of cancer. The role of Akt phosphorylation (pAkt) at Ser-473 on the outcome of patients with breast cancer who receive taxane-based chemotherapy has not been examined in clinical settings, including adjuvant chemotherapy. In a study published in JCO, Yang et al. hypothesized that pAkt predicts benefit from the sequential addition of paclitaxel to adjuvant doxorubicin plus cyclophosphamide (AC) chemotherapy in patients with node-positive breast cancer, participating in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-28 trial.

Primary tumors from the NSABP B-28 trial tissue microarray were available from 1,581 patients who were randomly assigned to receive either 4 cycles of AC alone, or followed by 4 cycles of paclitaxel. With a median follow-up of 9.1 years, there were no differences in disease-free survival (DFS) or overall survival (OS) with and without receiving paclitaxel among 975 patients with pAkt-negative tumors. In 606 patients with pAkt-positive tumors, the sequential addition of paclitaxel resulted in a 26% improvement in DFS or a 20% improvement in OS, which did not reach statistical significance. The study concluded that pAkt significantly predicts disease-free benefit from the sequential addition of paclitaxel to AC chemotherapy in patients with node-positive breast cancer. However, patients with pAkt-negative breast tumors do not appear to benefit from the addition of paclitaxel.

Source: JCO

 

A MicroRNA Targeting Dicer for Metastasis Control

Although specific microRNAs (miRNAs) can be upregulated in cancer, global miRNA downregulation is a common trait of human malignancies. The mechanisms of this phenomenon and the advantages it affords remain poorly understood. The findings published in Cell by Martello et al. provide evidence that cancer cells use global downregulation of the miRNA network to induce epithelial plasticity and foster invasive and metastatic behaviors. The authors identified a miRNA family, miR-103/107, targeting Dicer, a key component of the miRNA processing machinery that plays a causal role in these events.

The researchers found that in metastatic cells, high levels of miR-103/107 attenuate Dicer expression: this empowers invasive and metastatic properties without major impact on primary tumor growth. Thus, it appears that distinct cellular functions are differentially sensitive to Dicer fluctuations. miR-103/107 keep Dicer below a threshold required for metastasis protection. Conversely, the miRNA network sustaining tumor growth operates safely at lower Dicer levels. miR-103/107 are both generated by, and are regulators of, Dicer; this mutual feedback relationship allows to scale down Dicer levels, but is also intrinsically incompatible with complete depletion, maintaining sufficient Dicer for growth control and, likely, other cellular functions. Another significant finding was the association of the miR-103/107-Dicer pair with EMT (epithelial-to-mesenchymal transition). This suggests a new pathway by which Dicer inhibition drifts epithelial cancer toward a less differentiated, mesenchymal fate to foster metastasis. The positive effects of antagomiR-103/107 at least suggest that modulation of miR-103/107 by RNA-based therapeutics may prove clinically useful for the treatment of breast cancer.

Source: Cell

 

RT and Endpoint PCR Assays for Detecting Mutations in PI3K Oncogene

The PI3K pathway plays a significant role in colorectal, gastric, breast, and endometrial tumors, therefore, drugs inhibiting PI3K are a significant focus of current cancer drug development. Multiple scientific papers have shown that PI3K has the potential to be a clinically relevant biomarker for the prediction of individual response to specific cancer therapies. Diagnostic assays that detect mutations in PI3K will be an essential component of cancer drug development and personalized healthcare.

Roche has an ongoing program to develop a RT (real-time) PCR assay that detects mutations in the PI3K oncogene. The assay will run on Roche's cobas 4800 System, easy-to-use software that integrates sample preparation, amplification and detection, and results management. Roche has obtained a worldwide co-exclusive license for the biomarker PI3K from QIAGEN to develop these assays. Roche intends to make the PI3K PCR assay available to internal and external pharmaceutical partners for use in clinical drug trials.

Source: Roche

 

Monitoring Cancer Therapy Using RECAF Blood Test

BioCurex announced its first set of results supporting the use of RECAF blood test to monitor cancer therapy. RECAF is a receptor for AFP (Alpha-fetoprotein). It is normally expressed by developing cells during fetal and embryonic life, but not expressed in most adult normal cells, which makes this marker an oncofetal antigen (AFP and CEA, two commonly used cancer markers, are also oncofetal antigens). RECAF is found on most cancer cells, including breast, colon, prostate, and lung cancers, and therefore it may be applicable to a much larger patient population. RECAF can be used in blood tests to determine whether a patient has cancer.

The test included samples from 27 human patients with early stages of breast cancer, who were tested before and after surgery. As a control, 15 samples from healthy individuals were also tested. The RECAF blood test detected 26 of the 27 patients as positive for breast cancer (sensitivity = 96%) and 14 of the 15 healthy individuals (93% specificity) were negative at the standard 4,700 RECAF Units cutoff. At a cutoff of 5,500 Units, there were no false positives (all healthy individuals were negative, thus the specificity of the test was 100%). These results indicate that the RECAF test can detect 9 out of 10 women with early stages of breast cancer while being negative in all healthy individuals. While RECAF’s potential for cancer screening is important, the use of this marker for follow-up and monitoring of therapy is its most immediate application.

Source: BioCurex