Drug development for metastatic castration-resistant prostate cancer: current status and future perspectives

Prostate cancer represents a third of all newly diagnosed cancers in men in the USA with an estimated incidence of 192,280 cases and 27,360 deaths in 2009. It continues to be a major cause of cancer-related morbidity and mortality, and there is an urgent need for new treatments. Historically, systemic therapy options were limited after progression on docetaxel-based chemotherapy. This article reviews current data on the novel therapeutics demonstrating activity in metastatic castration-resistant prostate cancer and their future role in the treatment of this disease with a poor prognosis.     

Minimally invasive surgery and childhood cancer

Over the last 2 decades, minimally invasive surgery (MIS) has become a significant tool for the diagnosis and treatment of malignant disease in adults. Despite initial reports of port-site metastases and peritoneal spread following laparoscopic resection of colorectal cancer in the 1990s, MIS is now commonly used for many applications in adult surgical oncology, including biopsy and resection of malignant disease in the chest and abdominal cavities, mediastinal and retroperitoneal lymph node dissection, staging of abdominal, pelvic and thoracic malignancies, and management of therapeutic complications. The use of MIS techniques in children is growing with the availability of smaller instruments and equipment more suitable to the pediatric patient. Herein, we review the role of MIS in the diagnosis, staging and treatment of malignant disease in children. We will also evaluate MIS as it applies to the palliation of disease and the management of treatment complications in childhood cancer.     

Genomics in breast and prostate cancer: assessment of the current state and future perspectives

Genomic approaches to cancer are beginning to have an important impact in unraveling the complex etiologies of this disease, as well as allowing us to rationally treat afflicted patients. In this article, we will focus largely on genomic approaches to breast and prostate cancer susceptibility, as well as pharmacogenomic approaches to treatment. Current genomic approaches to cancer susceptibility have led to some significant, if not spectacular, successes which include breast cancer. More modest achievements, if not outright failures, such as in prostate cancer, are also notable and will be discussed further. We propose interdisciplinary approaches involving basic, clinical and population scientists to vigorously attack the cancer problem scientifically and with more organization. We highlight recent successes and suggest new approaches with a personal, if not provocative, perspective.     

Combining surgery and chemotherapy for invasive bladder cancer: current and future directions

More than 13,000 patients died from invasive bladder cancer in 2005 alone. Radical cystectomy is the most commonly prescribed treatment for patients with muscle-invasive bladder cancer, or for those with a nonmuscle-invasive disease that is refractory to intravesical therapy. Despite advances in surgical technique and improved understanding of the role of pelvic lymphadenectomy, 5-year survival probabilities suggest that improvements in treatment are necessary. The maturation of several randomized clinical trials on perioperative chemotherapy, and particularly neoadjuvant chemotherapy, clearly suggest that an integrated treatment program of systemic chemotherapy and definitive locoregional therapy may improve the outcome for bladder cancer patients. The next frontier is the molecular characterization of this spectrum of diseases that make up invasive bladder cancer and targeted therapeutics. Prospective validation of molecular markers and evaluation of novel therapeutic agents, alone or in combination with established cytotoxic agents, provide hope of better outcomes for bladder cancer patients.     

Combining surgery and chemotherapy for invasive bladder cancer: current and future directions

More than 13,000 patients died from invasive bladder cancer in 2005 alone. Radical cystectomy is the most commonly prescribed treatment for patients with muscle-invasive bladder cancer, or for those with a nonmuscle-invasive disease that is refractory to intravesical therapy. Despite advances in surgical technique and improved understanding of the role of pelvic lymphadenectomy, 5-year survival probabilities suggest that improvements in treatment are necessary. The maturation of several randomized clinical trials on perioperative chemotherapy, and particularly neoadjuvant chemotherapy, clearly suggest that an integrated treatment program of systemic chemotherapy and definitive locoregional therapy may improve the outcome for bladder cancer patients. The next frontier is the molecular characterization of this spectrum of diseases that make up invasive bladder cancer and targeted therapeutics. Prospective validation of molecular markers and evaluation of novel therapeutic agents, alone or in combination with established cytotoxic agents, provide hope of better outcomes for bladder cancer patients.     

Minimally invasive surgery for esophageal cancer

Esophageal cancer represents a major public health problem worldwide. Several minimally invasive esophagectomy (MIE) techniques have been described and represent a safe alternative for the surgical management of esophageal cancer in selected centers with high volume and expertise in them. This article reviews the most recent and largest series evaluating MIE techniques. Recent larger series have shown MIE to be equivalent in postoperative morbidity and mortality rates to conventional surgery. MIE has been associated with less blood loss, less postoperative pain, and decreased intensive care unit and hospital length of stay compared with conventional surgery. Despite limited data, conventional surgery and MIE have shown no significant difference in survival, stage for stage. The myriad of MIE techniques complicates the debate of defining the optimal surgical approach for treating esophageal cancer. Randomized controlled trials comparing MIE with conventional open esophagectomy are needed to clarify the ideal procedure with the lowest postoperative morbidity, best quality of life after surgery, and long-term survival.     

胃癌微创治疗之路

外科手术是目前唯一可能治愈胃癌的手段,但传统的开腹手术通常伴随较高的并发症率和死亡率,还会对患者术后的生活质量产生较大影响。而微创外科技术由于可有效减少手术创伤,加快术后恢复,因此对于医生和患者均具有很大的吸引力,今后或将替代传统的开腹手术。目前,胃癌微创外科技术主要向着两个不同的方向发展,即内镜下肿瘤切除和腹腔镜手术。不久的将来,前哨淋巴结导航技术和机器人手术也将为胃癌治疗提供更多选择。随着各种微创技术的不断发展,胃癌患者术后的生活质量将显著改善。目前,许多有关各种微创技术的高水平临床研究正在进行当中,胃癌微创外科必将在世界范围内广为接受,并快速发展。      

Minimally invasive surgery for breast cancer

Breast conservation surgery has become a standard operation as a minimally invasive surgery for breast cancer in Japan. Now sentinel lymph node biopsy (SLNB), day surgery, and endoscopy assisted surgery are being introduced as more minimally invasive surgeries for breast cancer. When blue dye and/or isotope are injected into the peri-tumoral breast gland, the sentinel lymph nodes (SLN) can be detected easily, and node negative patients can be selected with certainty. When no metastasis is found in SLN by frozen section, T1N0 breast cancer patients can be treated without lymph node dissection. Using this technique, day surgery for patients who have clinically node-negative small breast cancer (less than 1.5 cm in diameter) is performed under local anesthesia. We have developed an endoscopy assisted conservation surgery for breast cancer. Using endoscopy, partial or total glandectomy with radical axillary lymph node dissection is performed via a 5 cm skin incision on the middle axillary line. When the amount of glandectomy is over one third, we perform immediate reconstruction using the latissimus dorsi. These minimally invasive surgeries for breast cancer will result in a better quality of life for breast cancer patients.     

Minimally invasive therapy for bladder and prostate cancer

Recently, minimally invasive therapy has been a key word in the medical field. Many new therapies have been developed in the field of urology. In this area, bacillus Calmette-Guerin (BCG) instillation therapy, transurethral resection of the bladder tumor and intra-arterial infusion with irradiation therapy are noted as minimally invasive therapies for bladder cancer. Laparoscopic prostatectomy, brachytherapy, three-dimensional conformal radiotherapy (3D-CRT) and high-intensity focused ultrasound (HIFU) have also been developed as minimally invasive therapies for prostate cancer. Though the establishment of the validity of each treatment will still take time, the best treatment for each patient should be chosen case by case, including considerations of postoperative quality of life and economic efficiency.     

Positron emission tomography in diagnosis and management of invasive breast cancer: current status and future perspectives

[18F]fluorodeoxyglucose positron emission tomography (FDG-PET) is a metabolic imaging modality that has increasing applications in oncology, neurology, and cardiology. Among the oncology applications, breast cancer is one of the most extensively studied diseases. FDG-PET has been performed for diagnosis, staging, and restaging of invasive breast cancer and for monitoring responsiveness to therapies. At the present time, the results of FDG-PET in detection of primary breast cancer and axillary staging are mixed and inconclusive. However, results demonstrating the superiority of FDG-PET over anatomic imaging modalities in detection of distant metastasis, recurrence, and monitoring therapies are relatively well documented. These applications have been accepted by medical professionals and the public, as evidenced by a recent decision by the Centers for Medicare and Medicaid Services (formerly Health Care Financing Agency) to provide coverage for the procedure. Future trends in this exciting area include development of novel breast cancer-specific PET radiopharmaceuticals and use of dedicated breast PET technologies for scans of breast/axillary lesions. PET/computed tomography technology, which combines anatomic and molecular/biochemical information, is also rapidly proliferating and should help to further improve the management of patients with breast cancer. The role of FDG-PET in breast cancer is increasing and evolving, and this metabolic imaging modality, in conjunction with newer tracers and other anatomic imaging methods, should improve diagnosis and management of patients with breast cancer     

Imaging prostate cancer: current and future applications

Various treatment options are available for adenocarcinoma of the prostate--the most common malignant neoplasm among men in the United States. To select an optimum management strategy, we must be able to identify an organ-confined disease (in which local therapy such as surgery or radiation may be beneficial) vs prostate cancer beyond the confines of the gland (for which other treatment approaches may be more appropriate). At present, no standard imaging modality can by itself reliably diagnose and/or stage adenocarcinoma of the prostate. Standard transrectal ultrasound, magnetic resonance imaging (MRI), computed tomography, bone scans, and plain x-ray are not sufficiently reliable when used alone. Fortunately, advances in imaging technology have led to the development of several promising modalities. These modalities include color and power Doppler ultrasonography, ultrasound contrast agents, intermittent and harmonic ultrasound imaging, MR contrast imaging, MRI with fat suppression, MRI spectroscopy, three-dimensional MRI spectroscopy, elastography, and radioimmunoscintigraphy. These newer imaging techniques appear to improve the yield of prostate cancer detection and staging, but are limited in availability and thus require further validation. This article reviews the status of current imaging modalities for prostate cancer and identifies emerging imaging technologies that may improve the diagnosis and staging of this disease.     

Anti-angiogenesis therapy in cancer: current challenges and future perspectives

It has been nearly 9years since the FDA (Food and Drug Administration) approved the first anti-angiogenic drug (bevacizumab) for treatment of metastatic colorectal cancer. Other angiogenic inhibitors have since been approved or are in different stages of clinical trials. However, continued clinical and preclinical investigations have identified major drawbacks associated with the application of this class of agents, including inherent/acquired resistance and induction of tumor invasiveness. In addition, lack of thoroughly validated predictive biomarkers has been one of the major hurdles to stratify cancer patients and to monitor tumor progression and response to the therapy. Investigations in clinic and preclinical models have provided some molecular and cellular mechanisms for the above challenges. This review aims to provide a concise update from recent findings.     

Minimally invasive surgery for small breast cancer

BACKGROUND AND METHODS: So-called minimally invasive techniques make percutaneous eradication of breast tumors possible, thus leading to breast-conserving treatment (BCT) without surgery. This paper reviews and discusses the feasibility of minimally invasive techniques for breast cancer. RESULTS: Although a wide variety of ablation techniques have been investigated for the treatment of primary breast cancer, radiofrequency ablation (RFA) remains one of the most promising and potentially useful tools. RFA therapy results in effective cell killing in a predictable volume of tissue with a low complication rate. On the other hand, ultrasonography is useful for guiding the needle within the tumor but cannot predict the extent of thermal ablation accurately. Early post-procedural magnetic resonance imaging (MRI) may be useful for assessing whether complete tumor ablation has been achieved by RFA. Whether adequate ablation of the tumor has been achieved can be confirmed by extensive core needle sampling of the treated area. However, validation of the margin status is also important and this needs to be tackled in further studies. CONCLUSIONS: There are many problems that remain before RFA therapy can be considered for conventional treatment. Further studies are needed to determine whether the use of RFA alone for local treatment of primary breast cancer will result in local recurrence and survival rates equivalent to those seen with BCT.     

Personalizing prophylactic surgery in cancer: current practice and future perspectives from new genome-wide association studies

Recurrence rates of approximately 35–65% after nephrectomy in patients with localized or locally advanced renal cell carcinoma clearly underline the need for adjuvant treatment modalities. Adjuvant treatment with cytokines, hormonal treatment and radiotherapy has not shown survival benefit. The only Phase III trial revealing significant prolongation of progression-free survival was published in 2004. In this trial, targeting the immune system using an autologous tumor-cell vaccine provided clinical efficacy, but as yet, no standard adjuvant therapeutic approach is available. Recent advances in understanding the molecular biology of renal cell carcinoma led to the development of several targeted agents showing antitumor efficacy and prolongation of progression-free survival in patients with metastatic kidney cancer, but to date, no data are available regarding their applicability and efficacy in the adjuvant setting. However, controlled trials applying these drugs in the adjuvant setting have already started and, hence, the question is raised as to whether there is still a role for vaccination immunotherapy in the era of targeted therapies. In this paper, results from current Phase III trials and other relevant studies regarding adjuvant treatment in renal cell carcinoma are reviewed with special interest on adjuvant vaccination therapies, particularly regarding future options of this therapeutic approach.     

Immunotherapy in gastrointestinal cancer: The current scenario and future perspectives

Gastrointestinal cancers include colorectal, gastric, oesophageal, pancreatic and liver cancers. They continue to be a significant cause of mortality and morbidity worldwide. Current treatment strategies include chemotherapy, surgery, radiotherapy and targeted therapies. Immunotherapy has recently been incorporated in treatment regimens for some gastrointestinal malignancies and research into different immune modifying treatments is being carried out in this context. Approaches to immune modulation such as vaccination, adoptive cell therapy and checkpoint inhibition have shown varying clinical benefit, with most of the benefit seen in checkpoint inhibition. This review summarises recent advances and future direction of immunotherapy in patients with gastrointestinal malignancies.     

Glycoimmunomics of human cancer: current concepts and future perspectives

Future strategies for the treatment of human cancer require a full appreciation of the intracellular and extracellular changes that accompany neoplastic transformation. The changes may involve a variety of micro- and macro-molecules, including, but not restricted to, peptides, proteins (with sugar and/or lipid moieties), oligosaccharides, glycolipids (neutral or acidic, e.g., gangliosides), ceramides, fatty acids and other lipids. Although several therapeutic approaches have been well developed in recent years, most of the reported studies focus on proteins and peptides. Glycoantigens and lipoantigens have been neglected. Elucidation of the profiles and properties of all molecules associated with tumor progression is required to develop a successful strategy to treat human cancer. This review describes the unique immunomics of tumor-associated glycoantigens and explains why the field of glycoimmunomics may yield clinically important biomarkers and treatments for the management of human cancer.