Abstract: Despite the recent advances in its management using cytoreductive surgery and chemotherapy, ovarian cancer remains the most lethal gynecological malignancy. One possible treatment strategy that may improve patient outcome is the use of monoclonal antibodies (mAb) that selectively target tumor cells expressing tumor-associated antigens, and thus offer potential benefits such as avoiding the cytotoxic side effects in normal tissue caused by traditional chemotherapeutic agents. Based on the promising results of preclinical studies, various mAb are currently being evaluated in patients with ovarian cancer. Some of them have already demonstrated favorable clinical outcomes in phase I/II studies. However, in contrast to its use for hematological malignancies and certain solid malignancies such as breast and colorectal cancer, mAb-based therapy has not been convincingly proven to be clinically effective in patients with ovarian cancer. As the preclinical results of mAb's therapeutic effects on ovarian cancer have been encouraging, further investigations are needed to establish a more effective, specific, and less toxic treatment strategy for this malignancy. ... Read more

Abstract: Glioblastoma is the most common and most lethal primary brain tumor. While small progress has been made in treating this cancer in recent years, glioblastoma remains largely resistant to all existing therapies. It has been hoped that dissection of the genetics of this cancer would lead to more targeted and effective treatments, and new advances may finally be bringing this closer to fruition. Within the last few years, high-throughput efforts such as The Cancer Genome Atlas and a massive sequencing project have yielded novel insights and classifications of this dreaded cancer. The likely impact on care delivery in the clinic may only be a few years away. The rapid and exciting pace of advances in glioblastoma genetics has prompted this up-to-date review. ... Read more

Abstract: Standard anti-cancer therapeutic modalities like chemotherapy and radiotherapy evoke host's reactions that include involvement of the immune system. Elucidation of these mechanisms offers the double advantage of enabling a more rational choice of cytotoxic therapy and exploring the combination with immunotherapy. Radiotherapy, a well established local anti-cancer approach, is a particularly interesting partner for immunotherapy, since it can be harnessed to specifically modify the immunogenicity of the primary tumor and its microenvironment, in the attempt to generate an in situ immunization against a patient's own cancer. ... Read more

Abstract: No chemotherapy regimen showed a survival benefit better than 5-fluorouracil alone in a phase III trial for advanced gastric cancer in 1990s, and several new cytotoxic agents became available in late 1990s. Thereafter, a couple of phase III trials supported the substitution of infusional 5-fluorouracil by orally administered agents and the replacement of cisplatin by oxaliplatin in early 2000s. Furthermore, a substantial amount of information about the heterogeneity and the biological backgrounds of gastric cancer has been obtained from recent trials, and it is suggested that some cytotoxic agents would be well indicated. Trastuzumab has succeeded in showing a survival benefit for patients with Her-2 positive gastric cancer which accounts for about 10-20% of the cancer. This means that the door is opened to the new era of chemotherapy with molecular target agents and with individualization for advanced gastric cancer. The new approach in the development of molecular target agents, e.g., biomarker oriented strategy, for advanced gastric cancer should be studied in clinical trials in the near future. ... Read more

Abstract: Ovarian cancer is the leading cause of cancer death among gynecological malignances. Despite the initial successful multimodality therapy with cytoreductive surgery and subsequent combination chemotherapy, most patients with advanced disease will ultimately relapse and become incurable. For this reason novel therapeutic approaches for the treatment of this malignancy are urgently needed. Adoptive transfer of genetically modified autologous tumor-reactive T cells is a promising novel antitumor therapy for many cancers. T cells may be genetically modified ex vivo to express chimeric antigen receptors (CARs), which are artificial T cell receptors targeted to specific tumor antigens. The resulting T cells are thus programmed to recognize tumor cells. Ovarian carcinomas in particular appear to be suited to this therapeutic approach based on the fact that these tumors are relatively immunogenic, inducing an endogenous T cell response. Furthermore, the degree to which this endogenous T cell mediated immune response is evident correlates to long-term patient prognosis following surgery and chemotherapy. To this end, adoptive T cell immunotherapy strategies for the treatment of ovarian carcinomas appear to be particularly promising and are currently being investigated at several centers in both pre-clinical and clinical settings. ... Read more

Abstract: Treatment outcome for advanced-stage non-small cell lung cancer (NSCLC) is limited by empiric administration of cytotoxic chemotherapy. Recent advances in molecular genomics have revolutionized cancer management and, specifically, epidermal growth factor receptor (EGFR) mutation has become a potent biomarker for lung cancer, which predicts tumor response to and prolonged duration of disease control by EGFR tyrosine kinase inhibitors (TKI). The Iressa Pan-Asia Study (IPASS) is a randomized phase III study comparing gefitinib (EGFR TKI) with paclitaxel/carboplatin (standard chemotherapy) in Asian non-/light smokers with adenocarcinoma. Progression-free survival (PFS) in EGFR mutation-positive patients was longer with gefitinib than with chemotherapy (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36-0.64; p<0.0001); in EGFR mutation-negative patients, PFS was longer with chemotherapy than with gefitinib (HR 2.85; 95% CI 2.05-3.98; p<0.0001). The findings are confirmed by one single-arm study and three other randomized studies. It has become clear that personalized medicine for NSCLC is feasible. This small step towards personalized medicine represents a paradigm shift in the management of NSCLC. ... Read more

Abstract: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. About 50% of the patients present locally advanced or metastatic disease at the time of diagnosis. First line therapy usually consists of a combination of cisplatin or carboplatin with a third-generation agent (paclitaxel, docetaxel, gemcitabine, or vinorelbine) that results in less than 5% 5-year survival (Goldstraw et al., 2007). Recently a different approach based on histological subtype has been introduced in the first line treatment of NSCLC: in the non-squamous histotypes, cisplatin plus pemetrexed, compared to the cisplatin plus gemcitabine combination, showed a better outcome, leading to its introduction in the first line treatment setting. In recent years advances in the second and third line treatments have led to a prognostic improvement. Two cytotoxic agents, docetaxel and pemetrexed, are approved as NSCLC second line treatment, and a new class of drugs against specific molecular targets -- tyrosine Kinase inhibitors (TKI) -- has emerged as an alternative to conventional treatment. Many trials are ongoing to assess the activity of new drugs, alone or in combination with other agents, or new combinations of third-generation chemotherapeutic agents. ... Read more

Abstract: The loss of ability in controlling cell cycle leads to aberrant cell growth and is a hallmark of cancer cells. Cell cycle regulation and progression mainly rely on protein phosphorylation events, therefore cell cycle kinases have long been viewed as potential targets for anticancer strategies. Consistently, cell cycle kinases are often dysregulated in different types of human cancer. Despite years of research and attempts directed at inhibiting cell cycle kinases, none of these approaches has been successfully translated to the clinic to halt tumorigenesis. Here, we review several currently pursued strategies and highlight both current challenges and some recent findings, which might help to develop new, better conceived therapeutic approaches based on cell-cycle kinase inhibition. ... Read more

Abstract: Chronic lymphocytic leukemia (CLL) is a malignancy mainly affecting elderly people and is still considered an incurable disease. Despite recent advances in CLL treatment, relapse rates are high and often accompanied by the development of resistance towards conventional chemotherapy. Thus, new agents are needed for the treatment of these patients. In recent years, our understanding of the biological mechanisms driving CLL pathogenesis has considerably improved, and novel treatment strategies are arising. This review summarizes recent insights in CLL biology and describes several new agents and treatment strategies that are currently explored in pre-clinical studies and early-phase clinical trials. ... Read more

Abstract: A recent Japanese Gynecologic Oncology Group phase III clinical trial in patients with ovarian cancer receiving the conventional paclitaxel-carboplatin combination once every 3 weeks or "dose-dense" paclitaxel once a week with carboplatin once every 3 weeks has reported a large progression free survival advantage for the dose-dense therapy. Recent advances in the molecular understanding of ovarian cancer point to molecular differences between paclitaxel and carboplatin sensitivity which link to the status of BRCA genes -- so called familial and sporadic "BRCAness." It may be that the change in the way we use paclitaxel allows us to more effectively target the heterogeneity of such intrinsic sensitivity/resistance to these agents in the adjuvant therapy of ovarian cancer, leading to significant improvement in the management of the disease. ... Read more