Current Cancer Therapy Reviews - Volume 9, Issue 2, 2013

Bone is a common site for metastases in patients with advanced breast or prostate cancer, with greater than 65% of patients developing bone metastases. This is hypothesized to be related to the bone marrow microenvironment providing a favorable niche for cancer cell survival and growth. Circulating tumor cells (CTCs) can colonize bone marrow niches to become disseminated tumor cells (DTCs). Survival of DTCs in the bone marrow is a function of the unique microenvironment and the ability of these cells to acquire an osteoblast-like phenotype through a process known as osteomimicry. Detecting CTCs in blood or DTCs in bone marrow has been shown to independently predict for disease progression and worse clinical outcomes in patients with breast or prostate cancer. Therapies that reduce levels of CTCs and DTCs may improve clinical outcomes in these patients. Bisphosphonates are bone-targeted agents used to reduce the rate of skeletal-related events in patients with bone metastases. Bisphosphonates such as zoledronic acid have demonstrated potential anticancer activity, and zoledronic acid was recently shown to reduce the persistence and prevalence of DTCs in patients with breast cancer. Research is ongoing to further define the role of bone-targeted therapies in the treatment of cancer.

Lung cancer is the leading cause of cancer related deaths worldwide. The prevalence and frequent deaths associated with lung cancer are due in part to the lack of efficient methods to diagnose the disease progression at an early stage and lack of effective novel treatment strategies. Both genetic and epigenetic mechanisms coordinate in the regulation of transcription which in turn works in regulation of cell growth and proliferation. Numerous genetic and epigenetic changes have been found to be associated with the lung carcinogenesis. The genetic changes include chromosomal abnormalities, oncogene overexpression, mutations in the tumor suppressor genes, changes in DNA repair genes, microsatellite instability, changes in telomerase activity and retrotransposition. These genetic changes either alone or in combination with epigenetic modifications associated with lung cancers such as DNA methylation, histone modifications including histone acetylation and methylation as well as substitution by histone variants have been well studied in lung tumorigenesis. The current review also focuses to address the novel drugs being used in trials such as erlotinib, gefitinib, cetuximab and crizotinib in genetic therapy. Further, a combination of azacitidine, a DNA methyltransferases inhibitor, and entinostat, a histone deacetylases inhibitor, has shown important progress in combined epigenetic therapy against lung tumorigenesis. However, further in depth investigations could identify potential drugs against various types of lung cancer.

Magnetic Resonance Imaging (MRI) has established itself as the optimal method for assessing local staging in patients with rectal cancer. This is due to several factors including, most importantly, the ability to accurately delineate the mesorectal fascia and thus determine which rectal tumours threaten the circumferential resection margin (CRM). It is also able to assess depth of tumour penetration into the mesorectum and thus identify those tumours considered high risk for disease recurrence. MRI is the optimal imaging modality to assess local nodal involvement and extramural venous invasion, which has now been recognised as a poor prognostic factor for both local recurrence and overall survival rates. The use of MRI for evaluating tumours both during and after pre-operative therapies is of increasing importanceand can influence the timing of surgery if patients undergo pathological complete response or show aggressive disease warranting more intensive treatment. This review examines the current status of MRI in the local staging and management of rectal cancer. The focus of the review is to identify the important prognostic features demonstrated on MRI and to assess the influence of these tumour characteristics on treatment decision-making.

Pancreatic cancer is a devastating malignancy with a median survival of less than one year. The exceedingly poor prognosis for metastatic pancreatic cancer patients remains a significant unmet medical need and is an opportunity for development of novel therapeutic approaches incorporating gene therapy strategies. Barriers exist preventing effective gene therapy including low transfection efficiency, poor tissue penetrance as well as non-specific delivery. However, one specific strategy using synthetic short interfering RNA fragments holds great potential and recently demonstrated successful systemic delivery using a transferrin (Tf)-targeted cyclodextrin-based polymer nanoparticle. Various nanoparticle formulations are currently being optimized for systemic gene therapy approaches. In this review, we highlight the rapidly progressing field of gene therapy strategies that have the potential to enhance the care of patients with devastating malignancies such as pancreatic cancer and focus on systemic delivery strategies to overcome remaining hurdles limiting widespread clinical applications.

Background: With improved treatments, a large majority of children (>70%) with central nervous system (CNS) tumors will become long term survivors. These survivors are at risk for adverse long term outcomes, also known as ‘late effects.’ This realization has led to tremendous levels of large scale organizational resources being used to better characterize late effects in an effort to provide evidence-based long term survivorship care to these survivors. Methods: In this article, we present a summary of findings from the two largest survivorship cooperative research groups, the Childhood Cancer Survivor Study and the British Childhood Cancer Survivor Study. We have extensively reviewed the peer-reviewed articles published by these two cooperative groups who have collectively published large amounts of relevant data on late effects in over four thousand survivors of childhood CNS tumors. Results: Survivors of childhood CNS tumors are at risk for several late effects related to sensory complications, endocrinopathies, neurological issues, secondary malignancies, cardio-pulmonary issues, dental problems, neuro-cognitive deficits and decreased quality of life. Several risk factors contribute to the development of specific late effects including those related to inherent patient characteristics, primary malignancy and treatment modalities. Conclusions: Childhood CNS tumor survivors are at risk of developing a wide spectrum of late effects. Health care practitioners, patients and parents should be aware of them. Decisions regarding treatment should take risk factors into account. Appropriate guideline-based care should be provided to these patients. Identification of potential risk factors and subsequent late effects may guide the development of future treatment protocols.

Background: Aberrant activation of the Wnt signaling is one of the most common events in hepatocarcinogenesis. The aim of this study is to investigate the role of methylation modulated APC, AXIN2, APC2 and NKD2 genes expression silencing in hepatitis B virus (HBV) related heptocellular carcinoma (HCC). Methods: Eighty paired tumor and adjacent non-tumor tissues were collected from HCC patients with chronic HBV infection and underlying cirrhosis. The promoter CpG islands (CGI) methylation status of the above genes in paired tissues and 7 human hepatoma cell lines were quantitatively analyzed. Realtime RT-PCR was performed to determine the mRNA levels of these genes. Results: Compared to the adjacent non-tumor tissues, tumor tissues exhibited significantly increased APC hypermethylation both in frequency (56.2% vs. 78.7%, P = 0.0024) and in intensity (15.0% vs. 34.4%, P < 0.0001). Accordantly, APC expression in HCC tissues was significantly lower than that in non-tumor tissues (P = 0.0031). AXIN2 CGI hypermethylation in both non-tumor and tumor tissues were found 91.4% and 85.7% in frequency, and 31.6% and 32.5% in intensity, both were significantly higher than that in disease-free liver tissues (P = 0.0015 and 0.0008, respectively). Consistent with the methylation pattern, no statistical difference of the AXIN2 mRNA level between the paired tissues was observed. Intriguingly, stratified analysis revealed AXIN2 mRNA expression level in tumor tissues was significantly down-regulated in under 55-year-old male group (P = 0.0138) and lower AXIN2 mRNA expression level in tumor tissues implicated earlier onset age. In contrary, in over 55-year-old group, tumor tissues’ AXIN2 mRNA level increased in parallel with the increase of patients age (P = 0.019). No methylation-mediated inactivation of APC2 and NKD2 gene was observed in hepatoma cell lines. Conclusion: Our findings suggested that methylation caused APC and AXIN2 expression silencing might be involved in hepatocarcinogenesis arisen from cirrhotic liver.

Retroperitoneal liposarcoma is often asymptomatic but sometimes attention is drawn to the neoplasm due to clinical manifestations. These include fever, flu-like symptoms, nausea or vomiting due to pressure or hypoglycemia related to paraneoplastic disease. We present a rare case of a massive retroperitoneal liposarcoma presenting with refractory dry cough. The patient underwent resection of the mass with complete resolution of her cough. Histopathological examination of the mass demonstrated a well-differentiated tumor with myxomatous features. No evidence of metastatic disease to the lungs was observed. This case points to the need for a thorough and careful evaluation of unexplained cough.

INTRODUCTION: Breast cancer is a serious health problem; 1.3 million women worldwide will be diagnosed with breast cancer each year, 465,000 will die annually. In Mexico, the disease represents 49% of neoplasms in women. Metastatic disease is the main cause of death in women with breast cancer (BC) making it important to identify chemotherapy (CT) schedules that offer the best response rate and palliation. PATIENTS AND METHODS: From October 2009 to August 2011, 37 breast cancer patients previously treated for metastatic disease (BC) and a minimum of two prior CT lines were treated with gemcitabine (G) (Total dose 200mg) plus Cisplatin ( C ) (Total dose 50mg) weekly. Patients were included following histological confirmation of breast cancer as the primary site and disease had to be clinically measurable or determined according to the RECIST method by ultrasound or conventional computer tomography (CT). RESULTS: The median age was 52 years ; 92% were ductal carcinoma; all patients presented evidence of disease progression; received another treatment regimen and palliative chemotherapy in various lines; all patients were exposed to regimens with anthracyclines and 12 (32.4%) received taxanes. 51 % had received surgical intervention. The median metastatic site was 2 (range 1-4) the most frequent metastatic sites being the lung (35 %), liver (18.9 %) and central nervous system (16.2 %). CONCLUSION: The weekly administration of low-dose gemcitabine and conventional dose of cisplatin is an active and well-tolerated regimen with response rates similar to those reported in most other treatment options.