Current Cancer Therapy Reviews - Volume 7, Issue 4, 2011

Delivery of tumor-associated antigens (TAA) in a way that induces effective, specific immunity is a challenge in anti-cancer vaccine design. Circumventing tumor-induced tolerogenic mechanisms in vivo is also critical for effective immunotherapy. Effective immune responses are induced by professional antigen presenting cells, in particular dendritic cells (DC). This requires presentation of the antigen to both CD4+ and CD8+ T cells in the context of strong costimulatory signals. Lentiviral vectors have been tested as vehicles for both ex vivo and in vivo delivery of TAA and/or activation signals to DC, and have been demonstrated to induce potent T cell mediated immune responses that can control tumor growth. This review will focus on the use of lentiviral vectors for in vivo gene delivery to DC, introducing strategies to target DC, either restricting cell entry or gene expression to improve safety of the lentiviral vaccine or targeting dendritic cell activation pathways to enhance performance of the lentiviral vaccine. This highlights the potential of lentiviral vectors as a generally applicable ‘off-the-shelf’ anti-cancer immunotherapeutic.

T cell immune responses play a critical role in preventing and treating malignant tumors. The most effective way for stimulating potent T cell immunity is by genetic immunization with recombinant viral vectors. Recombinant lentivector has recently been studied as antigen delivery vehicle for stimulating potent T cell responses. Studies showed that lentivector immunization can induce remarkably potent and durable CD8 T cell responses possibly because of their high efficiency of transducing dendritic cells (DCs) and persistent antigen presentation. In this brief review, we summarized the recent findings on the basic mechanistic studies, especially on the role of DC subsets in lentivector immunization, and the potential applications of using lentivector immunization for tumor immunotherapy in preclinical animal models.

Urothelial cancer (UC) of the bladder is a relatively common disease seen in Americans, especially those who have significant tobacco exposure history. While the signs and symptoms of UC can be straight-forward (e.g., hematuria, irritative voiding symptoms), a complete work-up is required to appropriately stage each patient. The work-up of UC consists of: a high level of suspicion for patients with hematuria to prevent missed or delayed diagnoses; an exam under anesthesia; imaging studies; urinary markers and cytology; cystoscopy and transurethral resection of the bladder tumor (TURBT), as well as potential repeat TURBT to prevent understaging and residual disease.

Studies have shown that breast conserving surgery is as efficacious as mastectomy in the treatment of women with early stage breast cancer. Recent publications, however, have demonstrated an increasing number of women electing bilateral mastectomy when diagnosed with unilateral breast cancer. Several plausible reasons for this rising trend for bilateral mastectomy include increased awareness of breast cancer risk in the contralateral breast, increased use of breast MRI as a diagnostic tool and advances in reconstructive and mastectomy techniques. This review will focus mainly on the reconstructive options within the third probable reason for the increasing trend of bilateral mastectomy, advances in breast reconstruction and mastectomy techniques. The various options in breast reconstruction will be presented with a historical perspective, as well as a brief discussion on current mastectomy techniques in breast surgical oncology, as advances in both fields have likely influenced the rising trend of bilateral mastectomy in the United States.

Introduction: The optimal Anti-VEGF (vascular endothelial growth factor) and Anti-EGFR (epithelial growth factor receptor) antibody regimen to combine with chemotherapy in the first-line treatment for metastatic colorectal cancer remains to be better defined. Results from randomized controlled trials are variable. Methods: A meta-analysis was performed by searching PubMed, Cochrane Registry, major oncology conferences proceedings until February 2010 for randomized controlled trials of Anti-VEGF and Anti-EGFR in first-line treatment of metastatic colorectal cancer. Summary estimates of progression-free survival, overall survival, overall response rate and 60- day mortality were derived. Effect of k-ras status was stratified in trials involving Anti-EGFR. Results: Nine trials were included, including three anti-VEGF +/- chemotherapy, n=2422; four anti-EGFR %plus;/- chemotherapy, n=4348 and two anti-VEGF with chemotherapy +/- anti-EGFR, n=1601. Adding anti-VEGF to chemotherapy showed a 20-30% risk reduction in disease progression and mortality, and a higher response rate. Benefit of anti-EGFR was seen only in k-ras wild type patients with 20% reduction in disease progression and 10% reduction of mortality. Adding both antibodies to chemotherapy showed worse survival outcomes. Conclusion: Benefit of adding anti-VEGF in first-line metastatic colorectal cancer treatment is well pronounced. Combining anti-EGFR with chemotherapy showed significant increase in response rate and PFS in k-ras wild type patients. Adding both antibodies to chemotherapy appeared inferior regardless of k-ras status.

Bone loss and increased risk of fractures often result from treatment with antitumoral agents due to more or less severe reduction of bone remodeling. Although various anticancer treatments reduce or inhibit osteoclast activities, the balance of bone remodeling is usually not biased towards osteoblast activity. The activity of osteoclasts is coupled with the activity of osteoblasts. Consequently, inhibition of osteoclast activity often implies reduction of osteoblast activity as well, or vice versa. Depending on the antitumoral substance used, there are large differences in the actions of antitumoral substances on this balancing effect. The less broad the antiproliferative properties of anticancer agents are, and the more they act in a targeted way, the more they show specific effects on both osteoclasts and osteoblasts. However, osteopenia and osteoporosis common in cancer patients is not caused solely by the anticancer treatment. Metastasizing cancer cells in the bone may provoke increased osteoclastogenesis and disturb the bone remodeling balance. Moreover, cancer patients with localized squamous-cell head and neck cancer already show increased bone resorption and decreased bone mass independently of treatment, and smoking or drinking habits. And even carcinogenesis in the intestine and other sites can be prevented by antirheumatic substances that inhibit osteoclastogenesis and have an antiinflammatory action. The question thus arises as to how bone remodeling and cancer development are related. Is the anti-osteoclastic activity of antitumoral agents involved in the prevention of carcinogenesis, and part of the antitumoral activity? This review demonstrates that osteoclastogenesis and cancer may be related in a complex manner. Experimental studies suggest that anticancer agents exert their activity by inhibiting the signaling pathways commonly over-expressed in cancer cells, as well as in cells responsible for bone remodeling.

Background: Today, cancer treatment is one of challenges in health and treatment system of any country. With quick development of radiation therapy and chemotherapy in recent years, this question is brought up that which method is more perfect to treat cancer. Methods: Radiation therapy is consisted of several methods including external radiation therapy (e.g. CyberKnife, IMRT, IGRT, SBRT, BNCT, Vero, IORT, Gamma knife, Tomotherapy and Volumetric modulated arc therapy (VMAT)) and internal radiation therapy (e.g. brachytherapy, endoradiotherapy (target radionuclide therapy): radioimmunotherapy and peptide receptor radionuclide therapy) that any one has a special function in cancerous cells destroy. Results: Chemotherapy has still its place in cancer treatment and is used as a current and worldwide method. Nowadays, radiation therapy evolves with a surprising growth. By abandoning Cobalt-60, linear and circular accelerators which are able to accelerate particles, could be used for cancer treatment. CyberKnife, IMRT, IGRT, SBRT, VMAT, tomotherapy and Vero are the most advanced methods used to radiation therapy in all angles which had minimum mistake in radiation to the near intact tissues. Today, brachytherapy by increasing production of treatment radioisotopes by cyclotron and reactor is used in the world. Endoradiotherapy (Target radionuclide therapy): Radioimmunotherapy and peptidereceptor radionuclide therapy are two considerable methods in cancer treatment. Conclusion: In this review, we consider principals and application of radiation therapy in the early 21st century.

As therapeutic options and supportive care for the treatment of neoplastic disease have improved, there has been an associated increase in the incidence of leptomeningeal disease. In this review, the clinical presentation, natural history, diagnostic evaluation, and treatment options for this often devastating sequela of solid tumors, lymphoma, and leukemia will be summarized. The therapeutic efficacy of ionizing radiation, systemic agents, and intrathecal drugs will be examined from the existing literature. Additionally the pathophysiology, which in part defines the therapeutic limitations in approaching this patient population, will be discussed in order to assist in individualized clinical decision making.