Current Cancer Therapy Reviews

ISSN: 1573-3947

Current Cancer Therapy Reviews
Volume 3, Number 2, May 2007

Contents


Physical Activity and Cancer Prevention: Updating the Evidence. The Role of Oxidative Stress in Carcinogenesis Pp. 81-95
Joanna Kruk and Hassan Y. Aboul-Enein
[Abstract]


Working Towards the Development of Vaccines for the Treatment and Prevention of Early Breast Cancer Pp. 97-107
Robert E. Roses, Min Xu, Shuwen Xu, Ursula Koldovsky, Gilsoo Son, Gary K. Koski and Brian J. Czerniecki
[Abstract]


Relation Between Helicobacter Pylori Infection and Gastroduodenal Diseases Pp. 109-115
Antonio De Luca, Elisabetta Buommino, Lucrezia Manente and Maria A. Tufano
[Abstract]


Combination of Anti-EGFR Drugs and Other Molecular Targeted Agents as Anti-Cancer Strategy Pp. 117-126
Floriana Morgillo, Erika Martinelli, Teresa Troiani, Giampaolo Tortora and Fortunato Ciardiello
[Abstract]


Stage N2/IIIA Non Small Cell Lung Cancer: An Evidence-Based Review Pp. 127-139
Christopher B. Komanapalli, Charles R. Thomas, Jr. and Mithran S. Sukumar
[Abstract]


Large Granular Lymphocyte (LGL) Leukemia: Pathobiology, Diagnosis and Treatment Pp. 141-150
Edna Ku, Todd Alekshun, Thomas P. Loughran, Lubomir Sokol and Pearlie K. Epling-Burnette
[Abstract]




Abstracts

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Physical Activity and Cancer Prevention: Updating the Evidence. The Role of Oxidative Stress in Carcinogenesis
Joanna Kruk and Hassan Y. Aboul-Enein

Objective: Cancer has been hypothesized being influenced by oxidative stress. Physical activity may offer one means for the influence on possible mechanisms operating on malignancy development. Hypothesis holds that physical activity influences on cell homeostasis.

Design: Update the evidence on a link between physical activity and cancer of the colon, rectal and colorectal, breast, prostate, lung, endometrial and ovarian, using research studies published between 2004-2006. Review of the accumulated evidence for possible role of oxidative stress in cancer development.

Methods: Studies were identified through a systematic review of literature available on the NLM PubMed, Medline, Current Contents, Elsevier-Science Direct databases.

Results: The reduction in cancer risk associated with exercise and physical activity was more likely to be found in case-control studies than in cohort studies. The maximal magnitudes of the risk reduction reported were: 63% for colon, 38% for breast cancer, 80% for prostate, 32% for lung, 40% for endometrial, and 33% for ovarian cancer. The available data show that physical activity could modify the tissue redox balance.

Conclusion: Recent evidence on the physical activity and cancer risk relation confirms previous findings that moderate in intensity exercise and physical activity prevents against some types of cancer; the best evidence remains for colon and breast cancer. Regular exercise at moderate levels seems to increase level of antioxidant enzymes; this might partially explain the lower cancer risk among physically active people.


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Working Towards the Development of Vaccines for the Treatment and Prevention of Early Breast Cancer
Robert E. Roses, Min Xu, Shuwen Xu, Ursula Koldovsky, Gilsoo Son, Gary K. Koski and Brian J. Czerniecki

Recent studies of immune responses to pathogens have identified pathogen-associated molecular patterns (PAMPs) recognized by the innate immune system through specialized receptors called toll-like receptors (TLRs). Signaling through these receptors initiates robust immune responses. By exploiting TLR signaling pathways, immunity to tumor-associated antigens may be generated. Many tumor-associated antigens are involved in the regulation of tumor phenotype or carcinogenesis. Immune targeting of these antigens may either alter the tumor phenotype, yielding a more treatable tumor, or eradicate early tumor stem cells preventing tumor formation. The oncoprotein HER-2/neu, which is over-expressed in a significant number of pre-malignant breast lesions of ductal carcinoma in situ (DCIS), may provide such a target. Immune responses directed against HER-2/neu may eliminate the disease, make tumors more amenable to anti-estrogen therapy, or prevent escape of hormone-resistant tumor phenotypes. Effective breast cancer prevention in preclinical studies utilizing HER-2/neu transgenic murine models has stimulated interest in, and optimism regarding, protective breast cancer vaccines in humans. Induction of anti-HER-2/neu T cell (CD4+ and CD8+) and B cell responses has been demonstrated in an ongoing clinical study targeting HER-2/neu using a TLR agonist stimulated dendritic cell (DC) vaccine. Moreover, these vaccinations lead to reductions in both HER-2/neu expression and extent of DCIS. HER-2/neu expression and aromatase activity have recently been linked through the intermediary cyclooxygenase 2 (COX2). This convergence between growth factor and hormone mediated pathways reinforces the notion that a significant number of breast cancers may be prevented through effective immune targeting of HER-2/neu. As progress is made in the development of vaccines for breast cancer prevention, the contributions of immune-mediated effector and inhibitory mechanisms to the pathogenesis of HER-2/neu over-expressing breast cancers will need to be better understood.


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Relation Between Helicobacter Pylori Infection and Gastroduodenal Diseases
Antonio De Luca, Elisabetta Buommino, Lucrezia Manente and Maria A. Tufano

H. pylori is now recognized as one of the most common pathogens afflicting humans, correlated with socioeconomic status and age. In the developed world H. pylori is believed to affect about 50% of people.

H. pylori infection was found to be correlated with precancerous lesions, such as chronic atrophic gastritis in the stomach. A long time colonization of human stomach by H. pylori may lead to peptic ulcers, non-Hodgkin’s lymphoma of the stomach, gastric atrophy and distal gastric adenocarcinoma.

Balance between proliferation and apoptosis is the essential element in maintaining the integrity of gastric mucosa. The disturbance of this balance could result in either cell loss with mucosal damage and ulcer formation or cell accumulation leading to cancer development.

H. pylori has a colonization range restricted to gastric mucosa and produces a number of protein products including urease, cytotoxin, flagella, CagA, VacA, heat shock proteins and adherence factors that contribute to its ability to colonize, to avoid host defenses, and to inflict damage to the host. For example, strains that possess CagA or HspB are associated with increased severity of gastritis and with additional risk to develop atrophic gastritis and cancer, instead strains that possess VacA increase the apoptotic events in the gastric mucosa.

To know the exact cascade of events activated after H. pylori infection by these proteins, may help to develop new strategies to fight, or rather to prevent, gastric cancer and other common malignancies.


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Combination of Anti-EGFR Drugs and Other Molecular Targeted Agents as Anti-Cancer Strategy
Floriana Morgillo, Erika Martinelli, Teresa Troiani, Giampaolo Tortora and Fortunato Ciardiello

Novel therapeutic approaches targeting signaling pathways involved in cell proliferation, apoptosis, angiogenesis and metastasis have been under clinical development. Of many potential targets in adult solid tumors, the epidermal growth factor receptor (EGFR) has been the most extensively studied since its over-expression has been observed in several common solid tumors. However, the insurgence for resistance to drugs targeting the EGF-receptor has been described. The understanding of the mechanisms which are responsible of resistance to EGFR inhibitors could lead to the development of improved strategies to integrate anti-EGFR therapies. In this review, we will describe the latest new strategies developed to optimize the therapeutic effects of EGFR inhibitors, by exploring combinations with other molecular targeted approaches including other erbB family member inhibitors, drugs with different structure and mechanism of action, other tumor cell-directed signal transduction inhibitors, anti-angiogenic treatment modalities, and the use of broad spectrum EGFR tyrosine kinase inhibitors.


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Stage N2/IIIA Non Small Cell Lung Cancer: An Evidence-Based Review
Christopher B. Komanapalli, Charles R. Thomas, Jr. and Mithran S. Sukumar

Introduction: The N2 /IIIA Non small cell Lung cancer is a heterogenous group of patients with many differences within the stage that warrant different treatment strategies and have an individual prognosis that varies depending on the size, site and number of lymph node stations involved.

Method: Review of the pertinent current literature on the identification of the various subsets of N2 disease and their management and prognosis.

Discussion: Define the spectrum of N2 disease and characterize the subsets within the stage. Highlight the different management strategies and prognosis of the various N2 scenarios that are commonly seen. Examine the evidence for restaging after neoadjuvant therapy and the modalities that may be used.

Summary: A concise outline of the subsets within the N2/IIIA stage with their evidence based treatment and survival.


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Large Granular Lymphocyte (LGL) Leukemia: Pathobiology, Diagnosis and Treatment
Edna Ku, Todd Alekshun, Thomas P. Loughran, Lubomir Sokol and Pearlie K. Epling-Burnette

Clonal lymphoproliferative diseases of large granular lymphocytes (LGL) arise from both CD3-negative and CD3-positive cells, which define NK and T-LGL leukemia, respectively. Chronic neutropenia and anemia represent the most common clinical manifestation of these diseases but lymphocyte infiltration into bone marrow, spleen, and liver also occurs in some cases. The mechanism(s) responsible for expansion of the LGLs are unknown and the impact of lymphocytosis on the development of cytopenias is also incompletely defined. In this review, we discuss the incidence, clinical presentation, diagnostic criteria, and possible mechanisms of LGL leukemia pathogenesis. Despite the indolence of most cases of LGL leukemia, approximately 65% of patients will require therapy. There have been few controlled clinical trials conducted in this disease and long-term treatment is often required for sustained disease control. Novel therapies are primarily directed toward the targeted disruption of LGL leukemia survival. Conventional and novel therapeutics are discussed.