Current Cancer Therapy Reviews (v.5, #1)

1,444,920 new cases of cancer were projected in 2007 in the U.S., half of these patients are suffering from cancers of the prostate, the breast, the lung, and the colon/rectum. Colorectal and lung cancer are the most frequent solid tumors in both women and men. However, the US cancer statistics offer some hope. The incidence rates of colorectal and lung cancer rose till 1985 and 1991, respectively after which they fell. Global statistics is the one side of the coin but successful prevention and treatment of solid tumors requires the acceptance that these are not single diseases. This review focuses on the following topics: 1) Tumor biology: inflammation, growth factors (EGF, VEGF, IGF and its receptors), and epigenetic events. 2) Management strategies in diagnosis: Is early diagnosis feasible? a) Tumor-specific antigens. b) Radiological methods. c) Endoscopy. d) Contributions of pathology to diagnosis and treatment decisions. 3) Appropriate patient selection for treatment purposes. a) Evaluation of tumor tissue. b) Tumor staging. 4) Therapy sequencing: drugs, beams, surgery. 5) Clinical trials a) Phase I trials. b) What are the best inclusion criteria and endpoints? 6) The pipeline. 7) New drugs and manifold consequences. 8.) Prevention strategies. 9.) Future directions.

In modern clinical oncology there is a growing need to diagnose the presence of disease as soon as possible, even when symptoms are not yet present or are minimal, to identify the response to treatment in patients that have been treated and to detect improvement or worsening of the disease as early as possible. Conventional imaging methods that rely on morphologic or structural data are very precise in the delineation of lesions, but frequently present a limited diagnostic efficacy in the evaluation of response to oncologic treatments. These imaging methods define response to treatment as a reduction of tumor volume, without considering molecular or functional aspects that appear earlier than the structural or anatomic changes. Positron emission tomography (PET) and PET-CT with 18F-fluorodeoxiglucose (FDG) are very useful in monitoring response to treatment, following chemotherapy and radiotherapy. Many studies have demonstrated that FDG PET is an accurate method to correctly detect response to therapy. Moreover, early therapy response evaluation with FDG PET can predict response to treatment and patient outcome. This allows tailoring treatments to the individual patient depending on the chemosensitivity and radiosensitivity of the tumor. Therefore, FDG PET is a diagnostic imaging method that has the potential to improve the probability of cure or improvement and reduce the adverse effects and cost of unnecessary or ineffective treatments. In the research and development of new therapies, the non-invasive imaging methods used are of great importance, especially PET as it supplies functional and molecular information. PET can be used to assess all the processes related with the development of a new drug, especially assessing evolution and outcome. Here we present a review of the available evidence regarding therapy response evaluation with PET and PET-CT in non-small cell lung cancer.

Cellular and Molecular Mechanisms of Lymphangiogenesis and Lymphedema by Tomer Avraham, Peter Quartararo, Sanjay Daluvoy, Babak Mehrara (28-36).
Chronic secondary lymphedema is a potentially devastating condition affecting 90-150 million people worldwide. In the US, lymphedema is most commonly encountered in the upper extremity of women who have undergone axillary lymph node dissection for staging and treatment of breast cancer, though it may also occur following lymph node dissection for melanoma as well as certain gynecology oncologic operations. While a great deal has been elucidated about the biology of lymphatics, lymphatic development, and the lymphatic system in the past 20 years, considerably less is known about impaired lymphatic regeneration and the mechanisms that lead to secondary lymphedema. This deficit in knowledge presents a barrier to the development of effective treatments or prophylactic measures for chronic secondary lymphedema. Recent advances in this arena have showed that pathogenesis of lymphedema is complex, and that effective treatments for this often devastating condition will likely require the use of multiple modalities. In this review, we will discuss the development, anatomy, and physiology of lymphatics as means of introducing this system to the reader. Further, the latest advances in the scientific exploration of lymphedema and lymphatic regeneration will be presented.

Non-melanoma skin cancer (NMSC) is the most frequent malignancy in the United States, with over one million new cases reported annually. Approximately 80and#x25; of NMSC are basal cell carcinomas (BCC), while the remaining 20and#x25; of NMSC are squamous cell carcinomas (SCC). BCC and SCC commonly arise in regions of the skin subjected to chronic sun exposure implicating ultraviolet radiation (UV)-induced cellular damage as the primary causative agent. While surgical excision is an effective treatment of NMSC, strategies aimed at NMSC prevention have not been exploited clinically. The application of sunscreens has been the primary means of prevention by physically blocking the absorption of UV radiation. However, sunscreens have had limited success in decreasing NMSC incidence overall, necessitating more targeted strategies against UV damage. In this review we will discuss the relevance of recently identified UVinduced cellular changes, including induction of reactive oxygen species, immune modulation, and damage to mitochondrial DNA to serve as potential targets for the chemoprevention of NMSC. Finally, we will discuss the potential of genes required for the maintenance of epithelial stem cells in the skin as therapeutic targets for cutaneous cancer.

Purpose: To conduct a systematic review of available limited sampling strategies (LSSs) for all anticancer (other than platinum) agents and to assess the clinical utility of such models. Design: A literature search was conducted using PubMed and EMBASE up to November 2008. Relevant articles were then categorized according to modified level of evidence guidelines of the U.S. Preventive Services Task Force. Results: Fifty-one studies have been published suggesting LSSs for the estimation of pharmacokinetic (PK) parameters for 16 different anticancer agents. These include [number of studies (n) =1, unless otherwise denoted]: busulfan [levels II-1, II-2(n=6), III], cladribine (level II-1), cyclophosphamide (level II-1), docetaxel (level II-1, III), doxorubicin (level II-1), epirubicin [levels II-1, III(n=2)], etoposide [levels I(n=3), II-1(n=2), II-2, III], 5-fluorouracil [levels II-1, II-2, III(n=2)], irinotecan [levels I(n=2), II-2(n=3), III], melphalan (level I), methotrexate [level II-1(n=3), II-2], temozolamide (level I), thiotepa (level III), topotecan [levels I(n=3), II-1, II-2, III], vinblastine (level II-1) and vinorelbine [levels I, II-2(n=2)]. Conclusion: The 12 level I studies illustrate that when properly constructed and validated, LSSs have the ability to estimate PK parameters in cancer patients. However, the estimated PK parameters need to be related to clinical response or toxicity in order to demonstrate full clinical utility.

Current Status of Primary Cytoreductive Surgery for the Treatment of Advanced Epithelial Ovarian Cancer by Kaei Nasu, Harunobu Matsumoto, Noriyuki Takai, Hisashi Narahara (67-79).
Ovarian cancer is the third-most common cancer of the female reproductive tract, yet it has the highest case fatality ratio of all gynecologic malignancies. Approximately 60and#x25; of women diagnosed with epithelial ovarian cancer will die of the disease, because the majority of patients are diagnosed with advanced disease. Surgery followed by chemotherapy is the standard approach to the management of advanced epithelial ovarian cancer. The goal of the surgery is optimal cytoreduction prior to the initiation of chemotherapy. As significant survival benefit from optimal cytoreduction has also been shown for patients with advanced disease. The generally accepted definition of optimal cytoreduction today is a residual tumor diameter no greater than 1 cm. However, the surgeon should attempt to achieve complete cytoreduction to a level of no visible disease or microscopic disease. The surgical procedures required to achieve complete cytoreduction depend on the disease distribution. The most common areas of tumor involvement are the paracolic gutters, the small bowel serosal and mesentery surfaces, the diaphragmatic and pelvic peritoneum, the greater and lesser omentum with extension to the transverse colon, and the sigmoid colon affected by direct extension from the ovary. In cases of extensive tumor involvement, optimal cytoreduction may involve a radical en bloc resection of all involved pelvic viscera and associated peritoneum, bowel resection, splenectomy, and diaphragmatic and liver resection. The benefit of such aggressive surgery outweighs the risk of morbidity in the vast majority of patients. This paper is a review of the recent information concerning the definition of optimal cytoreduction, surgical techniques for maximum cytoreduction, and the selection criteria for patients.