The introduction of novel agents targeted to specific molecular targets of cancer cells offers more treatment options and improvement in outcome for exocrine pancreatic adenocarcinoma. Due to the limitations in the scope and scale of researches, this review of clinical studies presents the effects of administering the agents targeting the receptors or ligands of epidermal growth factor (EGF) or vascular endothelial growth factor (VEGF) to treat advanced pancreatic carcinoma. In addition, the basic knowledge on the mechanisms of therapy targeting EGFR and VEGFR were described. Among all agents, erlotinib has been approved by the U.S. Food and Drug Administration and incorporated in a number of treatment guidelines. It has been shown, in a randomized phase Ⅲ clinical trial reported by the National Cancer Institute of Canada, to extend survival when used in combination with gemcitabine;however,its use as monotherapy has not produced significant efficacy. Furthermore, results from a muiticenter randomized clinical trial has demonstrated that the combined utilization of erlotinib and bevaeimlmab, in current with gemcitabine significantly improved the progression-free survival, but has no significant effect on overall survival of patients with advanced pancreatic cancer. Other agents including cetuximab, bevaeizumab, sorafenib, sunitinib, etc. used along or in combination with chemotherapy are under active investigation.

Surgery remains the mainstay treatment modality for localized esophageal cancer;however,only 30% to 40% of patients are surgically resectable at the time of diagnosis.In addition,the long-term survival for patients with locally advanced esophageal cancer after complete resection is less than 20%.Although radiation is an effective treatment modality for localized esophageal cancer,the prognosis of patients after definitive radiotherapy is dismal.Chemoradiation therapy in combination with surgery can significantly improve the treatment outcome for patients with locally advanced esophageal cancer,and currently the multidisciplinary approach is considered the standard treatment strategy.This review summarizes the recently published literature,especially randomized clinical trials and meta-analyses on the treatment of esophageal cancer,and provides the following recommendation based on the results of scientific evidences:surgery alone should be considered as the standard treatment for clinical stage I and stage Ⅱ except for cervical esophageal cancer.For thoracic esophageal cancer,neoadjuvant chemoradiotherapy followed by complete resection should be considered for resectable locally advanced diseases.For medically inoperable and unresectable esophageal cancer,concurrent chemoradiation therapy should be considered as the standard treatment modality.For patients who were surgically treated without neoadjuvant therapy,the addition of definitive chemoradiotherapy to the definitive dose should be provided.

The development and progress of prostate cancer is hormone dependent. Currently, hormonal treatment remains the most important treatment modality for alleviating the symptoms caused by metastatic prostate cancer. Hormonal therapy for prostate cancer includes orchidectomy(with or without adrenectomy) or drug therapy. The most commonly prescribed hormonal therapy medication for prostate cancer is LHRH agonists. Whether total androgen block using LHRH agonist and androgen blocking agents (combined androgen blockade) is more effective than single agent LHRH agonist in the treatment of late stage prostate cancer is unknown. Second line hormonal treatment is effective for selected patients with hormone refractory prostate cancer (HRPC). Although certain chemotherapeutic agents such as taxol has shown its efficacy for prostate cancer, second line chemotherapy should be utilized prior to chemotherapy for HRPC.

The prognosis of patients with pancreatic cancer is dismal, especially at the advanced stage of the disease. Surgery is considered as the only curative treatment modality for pancreatic cancer;however, less than 20% of patients are candidates for curative surgical resection. Multidisciplinary management, including radiation therapy with concurrent chemotherapy, followed by systemic chemotherapy, is the treatment of choice for locally advanced pancreatic cancer. An early phase Ⅲ clinical trial conducted by GITSG (GI Tumor Study Group) has demonstrated a survival benefit for concurrent chemoradiation as compared to radiation alone in locally advanced disease. 5-FU,capacitabine and gemcitabine are the most investigated chemotherapy agents used with radiation. Currently thecombined use of gemcitabine and radiation therapy is under active investigation, and may provide substantial clinical advantage over other regimens. Multi-agent chemotherapy regimen used in concurrence with radiation has not demonstrated any significant effect but with severe toxicities. Conformal radiotherapy should be routinely used to treat locally advanced pancreatic cancer with doses of 45-50.4 Gy. The target of locally advanced pancreatic cancer is focussed on the gross tumor with safe margins. The use of IMRT is highly recommended for unresectable tumor, and makes further dose escalation possible.

Deifnitive treatment for locoregionally advanced squamous cell carcinoma of the head and neck region (HNSCC) is challenging, and usually require multidisciplinary efforts involving surgery, radiotherapy, and chemotherapy. Although surgery followed by radiation or chemoradiation therapy remains the standard treatment for resectable disease, combined chemoradiation therapy provides an effective option with organ spearing potential. In addition, combined chemoradiation therapy is the only treatment option for non-metastatic advanced HNSCC. Recently published results from TAX323 and TAX324, two important randomized clinical trials on the efficacy of induction chemotherapy using docetaxel based regimen, showed that induction chemotherapy using TPF can signiifcantly improve patients’ survival as compared to the conventional PF regimen. However, whether TP or TPF induction chemotherapy should be combined with concurrent chemoradiation and considered as part of the standard treatment regimen remains controversial, and requires support from the results of well-designed randomized clinical trial.

Advances in the understanding of cancer at the molecular level have led to much progress in the development of anti-cancer agents. Among the newly invented medications for targeted cancer therapy, protein kinase inhibitors target intracellular molecules crucial in signaling pathways for cancer cell survival, proliferation, and disease progression. The Raf serine/threonine kinases are pivotal molecules within the Raf/mitogen extracellular kinase (MEK)/extracellular signal-related kinase (ERK) signaling pathway. The exact function of Raf in normal human cells is not yet understood; however, preclinical and clinical researches have shown that over expression of Raf gene or overreaction of Raf kinase isoforms have critical roles in many types of solid tumors, including renal cell carcinoma, hepatocellular carcinoma, melanoma, and non-small cell lung cancer (NSCLC). Sorafenib is the first oral, multi-kinase inhibitor that targets the Raf kinases. It also has a broad spectrum activity against other receptor tyrosine kinases associated with vascular endothelial growth factor receptors and platelet-derived growth factor receptors. Sorafenib was recently approved by FDA for use in advanced renal cell cancer, and is currently undergoing active investigation in the treatment of other types of malignancies, such as melanoma, liver cancer, prostate cancer, and NSCLC. In this review, we will illustrate the role of Raf in both normal and malignant cells, the mechanism of sorafenib in the treatment of renal cell carcinoma, as well as clinical data that support its use and further investigation in advanced renal cell carcinoma, melanoma, and other tumor types.

Bone is the most common site for metastasis from prostate cancer, and bone metastases also is one of the main causes for the death of the patients with prostate cancer. Since the patients with bone metastases from prostate cancer still have relatively long survival periods after treatmemt, how to properly choose the treatment option for the metastatic patients is imperative in terms of improvements in both quality of life and life expectation. This paper summary pathophysiology, risk evaluation clinical assessment and the current status of the treatment options of prostate cancer with bone metastases, it also lays out the background for the individualized treatment plan that still needs to be further investigated.

Surgery is the only curative treatment modality for renal cell carcinoma (RCC). However, approximately 30% of patients who undergo successful nephrectomy for RCC will develop locoregional or metastatic recurrence. Effective treatment for recurrent or metastatic RCC is limited. It is known that conventional radiation therapy and chemotherapy are relatively ineffective for RCC patients with distant metastases. Although immune therapy with high dose interleukin can provide disease control for a portion of patients with advanced RCC, its therapeutic effect usually is not sustainable. In addition, substantial adverse effects and complications have limited the use of high dose interleukin treatment. Advances in the understanding at the molecular level of cancer have led to much progress in the development of anti-cancer agents, including drugs of targeted cancer therapy. Targeted therapy is not only effective in cancer treatment, but also has reduced adverse effects compared with conventional chemotherapy and immune therapy. Much progress in the treatment of advanced RCC by targeted therapy has been achieved in recent years. In this review, we will illustrate the roles, mechanisms and effects of several targeted therapy agents, including the two newly FDA-approved drugs, sorafenib and sunitinib, in the treatment of advanced renal cell carcinoma.

Pancreatic cancer is a highly malignant neoplasm with dismal prognosis. The risk of recurrence and metastasis remains high even for patients who have undergone radical dissection. Therefore, adjuvant therapy after "curative" resection is crucial. However, consensus on the optimal management of pancreatic cancer after surgery has not been reached. Both chemotherapy and concurrent chemoradiation therapy have been advocated. Yet, based upon the results of published phase Ⅲ trials, the consensus and standard strategy of adjuvant treatment after pancreatic cancer surgery is still undo" debate. According to the results of GITSG and RTOG trials, the mainstream in North American is adjuvant chemoradiation. However, based on the results of ESPAC-1 and CONKO-001 studies, the oncologists in Europe usually recommend chemotherapy alone. Furthermore, the superiority of gemcitabine over 5-FU in the adjuvant setting is largely unclear. This article reviewed the main results of the clinical trials in the field of adjuvant treatment of pancreatic cancer.From the authors' view, both the standard dosage of gemcitabine (CONCO-001) and chemoradiation (RTOG-9704) after resection of pancreatic cancer could be considered as candidates for adjuvant strategy. However, the optimal therapy will have to be determined by trials with larger number of patients.

To perform an evaluation of the on-going prospective clinical trials on particle radiation therapy and their impact on the current clinical practice as well as future clinical research and development.Furthermore,to briefly present the results of the registration trial of the IONTRIS particle therapy system at the Shanghai Proton and Heavy Ion Center.We used data from the clinicaltrials,gov and the Particle Therapy Collaborative Organization Group (PTCOG) website.After excluding retrospective and in silico studies,we examined and analyzed the prospective clinical trials for their ion type,targeting disease site,and nature.At the time of this analysis,149 prospective trials were identified on proton and carbon-ion radiation therapy,including 20 were carbon-ion and 129 trials were proton radiation focused,respectively.Except for 15 randomized phase Ⅱ/Ⅲ and Ⅲ trials,134 trials were phase 0-Ⅱ trials.Tumors from nearly all body parts were covered by the on-going trials,but trials on pediatric,GI,lung,prostate,and breast cancer account for the majority.The majority of the currently on-going trials focus on the efficacy and adverse-effects of the new dose/fractionation schemes of particle therapy as well as the use of particle therapy on new indications.Few studies invcstigate the addition of adjuvant therapy or imaging technology used in adjunct with particle therapy.Randomized trials that compare particle radiation therapy versus photon radiation is relatively uncommon.Despite the prevailing use of proton and heavy-ion radiation therapy for cancer treatment,～ 150 prospective clinical trials associated with particle radiation therapy are identified.As the majority of trials aim to investigate more efficacious dose/fractionation and the application of particle therapy on new indications,improved outcome from and expanded utilization of particle radiation therapy can be expected.