Current Cancer Therapy Reviews - Volume 7, Issue 3, 2011

Adverse pathologic features - including positive surgical margins, extracapsular extension, and seminal vesicle invasion - are common findings at radical prostatectomy for clinically localised disease. In the absence of further treatment, patients with such features are at high risk of biochemical and local recurrence and the development of metastatic disease. Radiotherapy is the only known curative treatment modality in patients with locally recurrent disease. Its optimal use following surgery, however, is controversial. In this review, the evidence for immediate (adjuvant) and selective early salvage approaches to postoperative radiotherapy are presented. The results of three randomized controlled trials comparing adjuvant radiotherapy to observation are discussed. The trial with the longest follow-up now demonstrates that, compared to a policy of observation, adjuvant radiotherapy prolongs overall survival and prevents distant metastases. It is not clear, however, whether this survival advantage would remain if adjuvant radiotherapy were compared to a strategy of close monitoring with salvage radiotherapy instituted at the time of biochemical failure. A selective salvage strategy has the advantage of avoiding ‘unnecessary’ radiotherapy, and its toxicity, for those patients destined not to fail after surgery. Large-scale randomized controlled trials comparing these two approaches are underway.

The failed outcome of autologous bone marrow transplantation for breast cancer opens the field for investigations. This is particularly important because the bone marrow could be a major source of cancer cells during tertiary metastasis. This review discusses subsets of breast cancer cells, including those that enter the bone marrow at an early period of disease development, perhaps prior to clinical detection. This population of cells evades chemotherapeutic damage even at high doses. An understanding of this population might be crucial for the success of bone marrow transplants for metastatic breast cancer and for the eradication of cancer cells in bone marrow. In vivo and in vitro studies have demonstrated gap junctional intercellular communication (GJIC) between bone marrow stroma and breast cancer cells. This review discusses GJIC in cancer metastasis, facilitating roles of mesenchymal stem cells (MSCs). In addition, the review addresses potential roles for miRNAs, including those already linked to cancer biology. The literature on MSCs is growing and their links to metastasis are beginning to be significant leads for the development of new drug targets for breast cancer. In summary, this review discusses interactions among GJIC, miRNAs and MSCs as future consideration for the development of cancer therapies.

The last two decades have been crucial for neurooncology due to the enormous progress in the base research and in the medical technology. Such a continuous development has significantly improved the knowledge on the genetics and molecular biology of brain tumors, thus allowing to better define their prognosis and to find new therapeutic targets. Furthermore, it has provided sophisticated diagnostic and therapeutic tools that have radically changed the behavior of neurosurgeons, neurooncologists, and radiotherapists with regards to these neoplasms. Once considered rare and poorly treatable, infantile brain tumors (IBTs) are currently more and more diagnosed and benefit of the aforementioned progresses so that their prognosis has become quite similar to that of the older ages. The aim of the present paper is to review the factors that favored these advances and to analyze the main aspects concerning IBTs, namely: Current information on epidemiology and etiology; - Advances in the neuroimaging; - Changes in the surgical attitude; - Development of ad hoc chemotherapic and radiotherapic protocols; - The role of pathology and molecular biology in the prognosis; - Outcome; - Future directions.

The objetive of this paper is to undertake a review of hormone therapy in localized or locally advanced prostate cancer. We have searched MEDLINE (1996-2009) for randomized or quasi- randomized controlled trials of patients with localised or locally advanced prostate cancer, that is, stages T1-T4, any N, M0, analizing: 1. Primary hormone therapy alone. 2. Neoadjuvant hormone therapy plus prostatectomy. 3. Neoadjuvant +/- concomitant hormone therapy plus radiotherapy. 4. Neoadjuvant hormone therapy plus radiotherapy plus adjuvant hormone therapy. 5. Adjuvant hormone therapy to primary curative intent. a. Radical prostatectomy and adjuvant hormone therapy. b. Radiotherapy and adjuvant hormone therapy. c. Adjuvant hormone therapy with bicalutamide. d. Duration of adjuvant hormone therapy to radiotherapy. 6. Early vs deferred hormonal treatment. 7. Hormone therapy and brachyterapy or cryotherapy. Until very recently it was known that endocrine therapy could improve progression free survival but few studies could demostrate a survival advantage in patients treated wih early endocrine therapy. Treatment of locally advanced prostate cancer (T3-4 N0 M0, T1-4 N1 M0) just with early androgen deprivation has shown not to be superior to deferred androgen deprivation in terms of neither overall nor prostate cancer specific survival. In locally advanced prostate cancer in order to gain benefit of early androgen deprivation, either radical prostatectomy or radiotherapy must be added. Results of several randomized and non-randomized clinical trials published in the English literature suggest that neoadjuvant hormone therapy prior to prostatectomy does not improve overall survival. The use of longer duration of neoadjuvant hormone therapy has any impact in patients survival. Patients treated with radiotherapy show a different outcome. Neo-adjuvant hormones prior to radiotherapy significantly improves both clinical disease-free survival and overall survival at 5 and 10 years.

The ribonucleoprotein, telomerase, prevents genomic instability by adding telomere repeats at the end of chromosomes. Although the telomerase RNA component (TERC) is ubiquitously expressed in mammalian cells, the telomerase reverse transcriptase subunit (TERT) is not expressed at easily detectable levels in most somatic cells but is expressed in most cancer cells. Targeting the up-regulation of TERT expression and/or enzymatic activity has gained considerable attention as a potential cancer therapy. Agents targeting the TERT component include nucleoside and nonnucleoside analogs as well as molecular inhibition of TERT using dominant negative protein expression or by ribozymes. Expression of the RNA component of telomerase has been targeted using RNA oligonucleotides. Additionally, peptide vaccines against telomerase have also been studied. Although several telomerase inhibitors have begun initial clinical trials for cancer therapy, none so far have entered clinical practice. Several aspects of telomere biology and telomerase action must be considered in designing anti-telomerase strategies for cancer treatment. These include expression of telomerase in normal somatic cells, the potential for selection of ALT (alternative lengthening of telomeres) clones, and the time-lag that is observed between initiation of treatment and appearance of cytopathic effect. However, knowledge of telomerase functions beyond telomere maintenance can provide insight into methods that may overcome limitations of telomerase- based therapies.

Skin cancer is the most common malignancy. Its pathogenesis is a multi-step, cumulative process which allows for potential intervention along the length of its spectrum. Cancer chemoprevention is a very promising approach to obtaining this goal. Unfortunately, its widespread application in clinic has been hampered by several problems, including systemic side effects especially if the medication requires prolonged use. For this reason, possible alternative measures have been investigated and are of great interest. The application of phytochemicals and other natural compounds is an appealing approach in that they are generally nontoxic, less costly and widely available. Topical application (e.g., transdermal systems, painting) of chemopreventives also serves as an alternative to systemic administration, and may limit side effects without sacrificing clinical advantages. The purpose of this paper is to provide an extensive investigation of the literature regarding current chemopreventative practices. This paper focuses discussions on the topical application of phytochemicals, by representing recent studies and findings. Based on recognition amongst the literature, five compounds are represented which include resveratrol, green tea, perillyl alcohol, ginger and inositol hexaphosphate. More compounds are also named with brief introduction, and further study is discussed.

Photodynamic therapy (PDT) is based on the use of a photosensitizing agent such as porphyrins, although the earliest descriptions of PDT involved the use of eosin. Many of the molecular details of PDT are unclear, while the basic premise of PDT is simple. A photosensitizing agent, either endogenous or exogenous, is exposed to an activating light source and in the presence of oxygen produces activated intermediates, primarily singlet oxygen. Singlet oxygen is a highly reactive molecule that oxidises carbon-carbon bonds and can damage various components of the target cell (e.g., lipids, nucleic acids, etc.) directly leading to cell death. Porphyrins preferentially bind to a receptor located on the outer mitochondrial membrane called the peripheral benzodiazepine receptor. Photoactivation leads to release of mitochondrial cytochrome c and increases levels of caspases 3 and 9. Caspase 3 plays a major role in apoptosis via protein cleavage. Currently, much research is underway to help identify adjuvant treatments to potentiate the photodynamic response. Active areas of investigation include the use of agents to facilitate cutaneous penetration of photosensitizing agents, amplify the response of macrophages and other inflammatory cells, decrease angiogenesis, inhibit matrix metalloproteinase and cycloxygenase II, and activate the complement cascade. The experimental evidence is that porphyrins accumulate in the tumour tissue. Our results indicate that phenylalanine and tyrosine are the amino acids that have the most affinity in binding HpD. Recently, our investigations in vitro have sought to reduce the side effects of PDT and cytostatic therapy by using reduced amounts of compounds with a high rate of toxicity in anti-cancer protocols.