Current Cancer Therapy Reviews - Volume 6, Issue 3, 2010

Cystic neoplasms of the pancreas account for about 10% of pancreatic tumors. Intraductal papillary mucinous neoplasms (IPMNs) are the most common cystic tumors of the pancreas presenting with no or unspecific clinical symptoms. Diagnosis of IPMNs is challenging and accomplished by CT, MRI, MRCP and EUS. Primarily, IPMNs are regarded as benign cystic lesions, however, almost 60% of resected IPMNs reveal malignant or invasive growth. The risk to progress to malignancy varies between 20-90% strongly depending on the origin of the lesion (main-duct type, branch-duct type) and clinico-pathological characteristics. Recently, first standardized algorithms for the treatment of IPMNs have been formulated, however, therapeutic consequences (surgical approach vs. surveillance strategy) are still controversial. This review provides a detailed overview of the currently discussed options for diagnostics, therapy and surveillance of IPMNs.

Prostate cancer is currently the most prevalent cancer among men in the United States and ranks second to lung cancer in terms of annual mortality. The androgen receptor (AR) is central to the initiation and growth of prostate cancer and to the therapeutic response to hormones. Although it has been known for many years that the expression and activity of AR is controlled by AR coregulators, the manipulation of endogenous AR coregulators to affect AR levels or function has not been widely exploited clinically. Coregulators are proteins that interact with AR to either enhance (coactivators) or reduce (corepressors) transcriptional activity. They act via a variety of mechanisms that provide potential therapeutic targets. The purpose of this article is to review the evidence for the deregulated expression and activity of AR associated coregulators in the progression of prostate cancer. The therapeutic use of these coregulators in both clinical and preclinical models is discussed with the aim of suggesting new modalities for prostate cancer treatment.

Hepatocellular carcinoma (HCC) is a leading cause of cancer related death both in the United States and worldwide. Proper management begins with identification of high risk individuals who may benefit from a screening program for HCC, since early detection of this cancer can lead to improved survival. Advances in radiographic technology and new staging systems that take tumor burden and clinical status into account allow patients to be more accurately stratified into proper treatment groups. Depending on the cancer stage, treatments such as radiofrequency ablation (RFA), surgical resection and liver transplantation offer a potential cure, while other treatments such as transarterial chemoembolization (TACE) can prolong life with HCC. New agents such as the oral multikinase inhibitor sorafenib show promise of slowing disease through utilization of molecular targeting. In this article, we will review management strategies of HCC, from diagnosis to treatment.

Sarcomas are inherently exacting to treat due to the diversity of histology and anatomic locations in which sarcomas may arise. Each anatomic site poses specific challenges for ensuring accuracy of target delineation. Image guided radiotherapy (IGRT) is a technique in which pretreatment images are obtained on a regular basis to evaluate tumor and/or organs at risk (OAR) locations relative to their position on the day of CT simulation. If the tumor/OAR is misaligned, the patient is repositioned to shift the tumor/OAR into its original location. In head and neck malignancies, inconsistency in neck rotation, tumor shrinkage, and patient weight loss may contribute to interfraction variability of tumor and OAR position [1-3]. Retroperitoneal sarcomas neighbor the kidney, small bowel and other vital structures. Similarly, paraspinal soft tissue sarcomas nestle the spinal cord. Positioning accuracy is imperative. In sarcomas of the extremities, the potential for rotational motion of the extremity can besmirch the reproducibility of daily set-up. In addition, the tendency for large field size in extremity sarcomas can hinder positioning accuracy [4]. Frequent confirmation of tumor location has the potential to impact outcome and decrease morbidity. This article reviews the role of image guided radiotherapy in soft tissue sarcomas.

The prognosis for patients with advanced gastric cancer (AGC) remains poor, and systemic chemotherapy is the main treatment option. Many clinical studies utilizing oxaliplatin-based regimens as first-line treatment for AGC have been conducted by Chinese investigators. However, there is no clear consensus concerning the role of oxaliplatin in AGC in Chinese patients. The aim of the present literature-based meta-analysis was to compare the efficacy and tolerability of oxaliplatin-based regimens with cisplatin-based regimens in Chinese patients with AGC. The search period included trials published between January 2003 and October 2007. A total of 116 trials were identified, of which 104 trials were excluded, and 12 trials were included in this meta-analysis. The present meta-analysis showed that oxaliplatin-based regimens may be associated with higher 1-year survival and objective response rates in Chinese patients with AGC compared with cisplatin-based regimens. Cisplatin was more frequently associated with nausea/vomiting and anemia, while peripheral neuropathy, which resolved over time, was more common with oxaliplatin. High quality, large-scale, randomized, controlled phase III trials are needed to accurately identify the therapeutic effect of oxaliplatin in Chinese patients with AGC.

The rapid progress in understanding the molecular biology of cancer has made a large impact on the design and development of novel therapeutic strategies prompted by the multi-factorial limitations of the current chemotherapeutic modalities. Given that the development of newer antineoplastic drugs continues to rely heavily on isolation from natural sources rather than applications based on rational drug design and combinatorial chemistry, fungal secondary metabolites rank high on the list of potential targets for the discovery of novel chemotherapeutic agents. They represent a diverse group of bioactive compounds characterized by their origin and biosynthetic pathways. Also, they serve as regulators, chemical messengers in developmental processes, or as antibiotics. A broad variety of fungal secondary metabolites possess potent antitumor activity. Alpha sarcin, gliotoxins, trichodimerol, L-lysine alpha-oxidase, fumagillin, declauxin, chrysanthones, fungal-derived low molecular weight inhibitors of angiogenesis e.g. TNP- 470, retamycin, daunorubicin, and doxorubicin all have been shown to exert potent antitumor activity. Inhibition of protein synthesis, induction of DNA breakage and apoptosis, as well as blockade of angiogenesis are examples of the multiple antitumor mechanisms of fungal secondary metabolites. The current review explores the potential use of fungal secondary metabolites as antineoplastic drugs with special reference to the novel hepatoma growth-inhibition factor that we recently characterized from Trichoderma viride.

Cutaneous melanoma (CM) is the fourth tumor in frequency, and that whose incidence increases faster. In half of the cases, CM arises from pre-existing nevi. CM is a highly heterogeneous tumor, whose degree of differentiation varies among different hosts, and such heterogeneity is probably based on the accumulation of mutations that determine transitions from normal melanocytic stem cells → mutated benign melanocytic stem cells → malignant melanocytic stem cells → clonogenic melanocytic cells. These populations may express different antigens and would therefore trigger the proliferation of different T and B cell clones. Early diagnosis is the clue for the cure of CM; when visceral metastatic disease is established, the prognosis is somber. This is especially so since CM is quite resistant to chemotherapy, and some of the reasons for such resistance will be discussed here. However, CM has proved to be sensitive to immunological effectors, although the mechanism of such sensitivity is still being investigated. These effectors range from therapeutic vaccines, in vitro expanded cytotoxic lymphocytes, cytokines, and monoclonal antibodies. Finally, we will discuss new therapeutic approaches that include the combination of immune modulators and vaccines which are being assayed in light of recent tumor immunology research.

Total mesorectal excision (TME) for rectal cancer is now considered standard in the surgical treatment of rectal cancer. The application of this technique has resulted in a pooled pelvic recurrence rate of approximately 7%. Preoperative and postoperative radiation further decreases the local regional recurrence (LRR) rate in patients with rectal cancer but the reduction in risk is counterbalanced by increased short and long term toxicity. Lower LRR rates have not uniformly translated into more favorable overall survival. In addition, advances in imaging have resulted in more accurate pretreatment staging and have improved the ability to stratify patients based on risk of recurrence. Given low pelvic recurrence rates after TME-based surgery alone, the risks and toxicities of pelvic radiation, and superior imaging to select high risk patients, radiation may not be requisite in the treatment of all rectal cancer patients. In this review, we discuss the current status of radiation and LRR rates in rectal cancer after definitive surgical resection with respect to specific subsites and stages of disease, examine the impact of imaging in the selection of patients for radiation, and raise the possibility that predictive biomarkers may help to identify patients who may not require pelvic radiation.

Paralleling breast conservation therapy for invasive breast cancers, treatment for ductal carcinoma in situ (DCIS) has followed the treatment paradigm of surgery and postoperative radiotherapy. Randomized studies evaluating the need for radiation therapy following lumpectomy in patients with DCIS from both the NSABP (B-17) and the EORTC (10853) demonstrated a local control benefit that was homogeneous across all treatment groups. In an era of medicine driven by characterization of tumors into molecular subsets and increasingly focused on individualizing treatment, this “one size fits all” mentality has been challenged. With respect to invasive disease, it has become clear that while prospective randomized studies continue to show a reduction in local recurrence with the addition of postoperative radiation therapy, the magnitude of benefit varies among subsets of patients. The variability in the magnitude of benefit from postoperative radiotherapy was additionally demonstrated in a study showing further reduction in recurrence risk with the addition of a boost following whole breast treatment for invasive disease. In DCIS large randomized trials evaluating the additional efficacy of a boost and which subsets of patients would benefit the most, are lacking. While an international trial evaluating the benefit of a boost in patients with DCIS continues to accrue, the question of the risk:benefit ratio with the use of a boost and whom it will best serve remains unanswered.