Extracellular Activity of Cyclic AMP–Dependent Protein Kinase as a Biomarker for Human Cancer Detection: Distribution Characteristics in a Normal Population and Cancer Patients

Abstract

The overexpression of cyclic AMP (cAMP) -dependent protein kinase (PKA) has been reported in patients with cancer, and PKA inhibitors have been tested in clinical trials as a novel cancer therapy. The present study was designed to characterize the population distribution of extracellular activity of cAMPdependent protein kinase (ECPKA) and its potential value as a biomarker for cancer detection and monitoring of cancer therapy. The population distribution of ECPKA activity was determined in serum samples from a Chinese population consisting of a total of 603 subjects (374 normal healthy volunteers and 229 cancer patients). The serum ECPKA was determined by a validated sensitive radioassay, and its diagnostic values (including positive and negative predictive values) were analyzed. The majority of normal subjects (>70%) have undetectable or very low levels of serum ECPKA. In contrast, the majority of cancer patients (>85%) have high levels of ECPKA. The mean ECPKA activity in the sera of cancer patients was 10.98 units/mL, 5-fold higher than that of the healthy controls (2.15 units/mL; P < 0.001). In both normal subjects and cancer patients, gender and age had no significant influence on the serum ECPKA. Among factors considered, logistic analysis revealed that the disease (cancer) is the only factor contributing to the elevation of ECPKA activity in cancer patients. In conclusion, ECPKA may function as a cancer marker for various human cancers and can be used in cancer detection and for monitoring response to therapy with other screening or diagnostic techniques. (Cancer Epidemiol Biomarkers Prev 2007;16(4):789 -95)

Diversity of Bisubstrate Binding Modes of Adenosine Analogue–Oligoarginine Conjugates in Protein Kinase A and Implications for Protein Substrate Interactions

“…In recent years, PKAc has also gained interest as a diagnostic biomarker, due to association of its overexpression and secretion to blood plasma with several forms of cancer. 28 On the other hand, the ubiquitous and essential nature of cAMPregulated cellular processes renders PKAc an 'antitarget' for most protein kinase inhibition strategies.…”

Bisubstrate Inhibitors of Protein Kinases: from Principle to Practical Applications

“…[2] Inhibitors of PKs may have therapeutic use against cancer and other diseases by affecting certain regulators of molecular events, as well as for diagnosis and monitoring of PK-related diseases in the early stages. [3] Currently, ten small-molecule PK inhibitors are approved for medical use, and more than fifty are at various stages of clinical trials as anticancer drugs. [4] The majority of PK inhibitors developed are ATP-site directed, with generally good affinity, however, selectivity is poor due to the high homology of ATP-binding sites of PKs.…”

Higher Prevalence of Secretory CSE1L/CAS in Sera of Patients with Metastatic Cancer

“…These proteins may be useful for screening, cancer diagnosis and prognosis, assessment of therapeutic responses, and monitoring for cancer recurrence. Thus, secreted cancer cell markers are highly beneficial in the diagnosis and treatment of cancers (1)(2)(3)(4)(5)(6)(7).…”