Tumor Markers in Breast Cancer – Evaluation of their Clinical Usefulness

Breast cancer is the most common neoplasm affecting women in the Western world. Many studies are still conducted with the purpose of finding markers that could be used for early diagnosis and/or serve as possible reliable prognostic or predictive parameters, but with conflicting results. At present, no markers are available for an early diagnosis of breast cancer. For surveillance of patients with diagnosed breast cancer the most widely used serum markers are CA 15-3 and CEA which, in combination with other clinical parameters, could have clinical significance. The most useful and clinically important tissue-based markers in breast cancer are estrogen and progesterone receptors, used as a basis for hormonal therapy, and HER-2 receptors, essential in selecting patients for the treatment with Herceptin®. New or potentially new markers for breast cancer include BRCA1 and BRCA2 genes for selecting patients at high risk of developing hereditary breast cancer, as well as urokinase plasminogen activator and inhibitor for assessing prognosis in lymph node-negative patients. Results of tumor and patient genetic analyses including their clinical evaluation will enable application of more individualized and personalized approach in diagnosis and therapy of breast cancer patients

The growing relevance of cap-independent translation initiation in cancer-related genes

Twomainmechanisms for eukaryotic initiation of protein synthesis have been described – the canonical cap-dependent and the alternative cap-independent. They mainly differ in their requirement for 7-methylguanosine cap at 5’ end of mRNAmolecules to initiate translation. In cap-independent translation initiation, an element within 5’ untranslated region (5’UTR) ofmRNA, defined internal ribosome entry site (IRES), recruits 40S ribosomal subunit directly or close to the start codon without the need for the 5’ cap. Some cellular mRNAs – including those encoding for a number of growth factors, oncogenes, receptors, survival proteins, transcription and translation factors – contain IRES elements within their 5’ UTR what may allow them to be translated under different physiological or stress conditions (e.g., amino acid starvation, apoptosis, growth arrest, heat shock,mitosis, radiation) when global cap-dependent protein synthesis is suppressed. IRES-dependent translationmay escape the control of checkpoints present in cap-dependent regulation causing improper protein synthesis that can lead to cell apoptosis or disease. A growing number of cancer-related genes have been reported whose translation initiation depends on the presence of IRES element in their mRNA. These findings make the quest for discovering and testing new putative cellular IRESes even more meaningful. A deeper understanding of the role of IRES-dependent translation initiation in cancer etiology could ultimately give us a novel targets for cancer therapy

Tumor Markers in Breast Cancer – Evaluation of their Clinical Usefulness

Breast cancer is the most common neoplasm affecting women in the Western world. Many studies are still conducted with the purpose of finding markers that could be used for early diagnosis and/or serve as possible reliable prognostic or predictive parameters, but with conflicting results. At present, no markers are available for an early diagnosis of breast cancer. For surveillance of patients with diagnosed breast cancer the most widely used serum markers are CA 15-3 and CEA which, in combination with other clinical parameters, could have clinical significance. The most useful and clinically important tissue-based markers in breast cancer are estrogen and progesterone receptors, used as a basis for hormonal therapy, and HER-2 receptors, essential in selecting patients for the treatment with Herceptin®. New or potentially new markers for breast cancer include BRCA1 and BRCA2 genes for selecting patients at high risk of developing hereditary breast cancer, as well as urokinase plasminogen activator and inhibitor for assessing prognosis in lymph node-negative patients. Results of tumor and patient genetic analyses including their clinical evaluation will enable application of more individualized and personalized approach in diagnosis and therapy of breast cancer patients