Locally advanced nasopharyngeal carcinoma: Current and emerging treatment strategies

Although nasopharyngeal carcinoma (NPC) is a widespread malignant tumor, it is particularly frequent in Southeast Asia. Although T1 tumors can be effectively controlled with exclusive radiotherapy, this treatment modality is insufficient for most NPC patients, who present with locally advanced disease at diagnosis. In fact, for stages ranging from T2b N0 to T4 N3, definitive scientific evidence supports the use of concurrent platinum-based chemotherapy with standard external beam radiotherapy. This treatment approach has shown a statistically significant advantage in terms of overall survival, with respect to radiotherapy alone. Several trials have also investigated the use of neoadjuvant and adjuvant chemotherapy in combination with radiotherapy or chemo-radiotherapy. Platinum compounds, anthracyclines and taxanes are among the chemotherapy agents employed. This review focuses on the clinical results obtained in the field of adjuvant/concurrent/neoadjuvant chemotherapy for locally advanced NPC, for which exclusive concurrent chemo-radiotherapy currently represents the standard treatment approach.     

Radiation therapy for patients with locally advanced pancreatic cancer: Evolving techniques and treatment strategies

Despite ongoing efforts, patients with locally advanced pancreatic cancer (LAPC) continue to have a dismal prognosis. Such tumors are unresectable, and optimal treatment with chemotherapy and/or radiation therapy is still not established. While chemotherapy is conventionally aimed at preventing metastatic spread of disease, radiation therapy acts locally, improving local control which can potentially improve overall survival and most importantly quality of life. Here, we aim to review the primary literature assessing the role of diverse radiation therapy strategies for patients with LAPC.Many radiation regimens can be considered, and no standard treatment has demonstrated a clear improvement in clinical outcomes. We advise that the modality of choice be dependent on the availability of equipment, the dose and fractionation of treatment, as well as the dose received by normal tissue. Moreover, a candid discussion with the patient concerning treatment goals is equally as essential. Three notable strategies for LAPC are intensity-modulated radiation therapy, volumetric modulated arc therapy, and proton. These radiation modalities tend to have improved dose distribution to the target volumes, while minimizing the radiation dose to surrounding normal tissues. Stereotactic body radiation therapy can also be considered in LAPC patients in cases where the tumor does not invade the duodenum or other neighboring structures. Because of the high doses delivered by stereotactic body radiation therapy, proper respiratory and tumor motion management should be implemented to reduce collateral radiation dosing. Despite improved clinical outcomes with modern radiation modalities, evolving techniques, and more accurate planning, future studies remain essential to elucidate the optimal role for radiation therapy among patients with LAPC.     

Emerging therapeutic targets for patients with advanced prostate cancer

Although recent advances in the treatment of castration-resistant prostate cancer (CRPC) have significantly improved patient outcomes, advanced prostate cancer is still associated with substantial morbidity and mortality, particularly in patients who develop resistance after multiple lines of therapy. Various cell signaling, DNA repair, and epigenetic enzymatic pathways are being targeted with small-molecule inhibitors in order to identify treatment strategies for patients with CRPC. In this review, we discuss novel targets and agents, studied preclinically and now being validated in clinical trials, including poly ADP-ribose polymerase (PARP), enhancer of zeste homologue 2 (EZH2), hedgehog pathway, MDM2/p53, and tyrosine kinase inhibitors. Further, we outline current approaches for novel prostate cancer vaccines such as DCVAC/PCa, PROSTVAC-V/F, MVI-816, CV9104, and PF-06753512. This wide spectrum of potential treatment strategies holds promise for additional improvements in the treatment of patients with CRPC, as these novel agents are aimed at targets known to be associated with growth and malignant progression of prostate cancer. If primary study endpoints are met, findings from ongoing phase III trials of well-tolerated and active combinations may provide new effective treatment options for advanced prostate cancer and thereby contribute to enhanced disease control in CRPC patients.     

Multimodal treatment strategies for locally advanced rectal cancer

This review outlines the important multimodal treatment issues associated with locally advanced rectal cancer. Changes to chemotherapy and radiation schema, as well as modern surgical approaches, have led to a revolution in the management of this disease but the morbidity and mortality remains high. Adequate treatment is dependent on precise preoperative staging modalities. Advances in staging via endorectal ultrasound, computed tomography, MRI and PET have improved pretreatment triage and management. Important prognostic factors and their impact for this disease are under investigation. Here we discuss the different treatment options including modern tumor-related surgical approaches, neoadjuvant as well as adjuvant therapies. Further clinical progress will largely depend on the broader implementation of multidisciplinary treatment strategies following the principles of evidence-based medicine.     

Multimodal treatment strategies for locally advanced rectal cancer

This review outlines the important multimodal treatment issues associated with locally advanced rectal cancer. Changes to chemotherapy and radiation schema, as well as modern surgical approaches, have led to a revolution in the management of this disease but the morbidity and mortality remains high. Adequate treatment is dependent on precise preoperative staging modalities. Advances in staging via endorectal ultrasound, computed tomography, MRI and PET have improved pretreatment triage and management. Important prognostic factors and their impact for this disease are under investigation. Here we discuss the different treatment options including modern tumor-related surgical approaches, neoadjuvant as well as adjuvant therapies. Further clinical progress will largely depend on the broader implementation of multidisciplinary treatment strategies following the principles of evidence-based medicine.     

Ovarian cancer stem cells: elusive targets for chemotherapy

Ovarian cancer is one of the major causes of death in women with gynecologic malignancy. Most patients respond favorably to platinum therapy, but relapses are common. There is emerging evidence that a special subset of cells that is highly tumorigenic is responsible for recurrence of the disease. This subset of cells has been characterized by several groups and has been found to have the properties of cancer stem cells. They have been isolated from tumor samples obtained during surgical cytoreduction and also from the ascitic fluid of ovarian cancer patients. Currently, there are no known unique markers to define these cells, but several groups have used different approaches to purify them. Although some heterogeneity has been observed in these cells, most of them satisfy the functional definition of a stem cell. Advances in characterization of ovarian cancer stem cells are instrumental in developing therapies that specifically target them. This review describes the advances made in characterization of these cells, basis of their resistance to conventional chemotherapeutic agents and the prognostic implications of utilizing mechanisms specific to ovarian cancer stem cell for therapeutic interventions. Eliminating ovarian cancer stem cells could possibly lead to a prolongation of the disease-free survival period and hopefully a definitive cure.     

Hematological cancer in 2011: New therapeutic targets and treatment strategies

2011 saw improvements in our understanding of B-cell malignancies: insights into the genomic basis of chronic lymphocytic leukemia were achieved; reduced treatment intensity caused fewer toxic effects in early-stage Hodgkin lymphoma; first-line rituximab maintenance therapy improved outcome in follicular lymphoma; and selected patients with diffuse large-cell lymphoma benefited from the addition of bortezomib.     

Gonadotropin-releasing hormone receptors as molecular therapeutic targets in prostate cancer: Current options and emerging strategies

Prostate cancer is androgen-dependent in its early stages and androgen deprivation therapy represents the most effective first-line therapeutic approach. However, after an initial remission, prostate cancer progresses towards the castration resistant prostate cancer (CRPC) stage, with increased malignancy and resistance to conventional chemotherapy.     

癌症治疗的新兴免疫靶点及相关研究进展

免疫检查点是在机体自身免疫和抗肿瘤作用之间维持平衡的一系列重要因子,通过配体/受体相互作用可识别和启动多条免疫检查点通路,在维持自身免疫耐受和机体免疫稳态中起关键作用,但肿瘤细胞可以利用该途径逃避免疫监视。因此,免疫检查点阻断(immune checkpoint blockade,ICB)通路能够增强抗肿瘤免疫反应,免疫检查点抑制剂应运而生。随着免疫疗法在肿瘤治疗领域取得的重大突破,免疫检查点抑制剂受到越来越多的关注,许多新兴免疫靶点脱颖而出,极具应用前景和临床价值。本文就部分新兴的免疫治疗靶点的特性及相关研究进展进行综述。     

Cyclin-dependent kinases as new targets for the prevention and treatment of cancer

Based on the frequent aberration in cell cycle regulatory pathways in human cancer by cdk hyperactivation, novel ATP competitive cdk inhibitors are being developed. The first two tested in clinical trials, flavopiridol and UCN-01, showed promising results with evidence of antitumor activity and plasma concentrations sufficient to inhibit cdk-related functions. Best schedule to be administered, combination with standard chemotherapeutic agents, best tumor types to be targeted, and demonstration of cdk modulation from tumor samples from patients in these trials are important questions that need to be answered to advance these agents to the clinic.     

Ovarian cancer: strategies for overcoming resistance to chemotherapy

Ovarian cancer is responsible for 4% of deaths from cancer in women. Treatment comprises a combination of surgery and chemotherapy, but patients typically experience disease relapse within 2 years of the initial treatment. Further treatment can extend survival, although relapse eventually occurs again. A better understanding of the mechanisms that underlie this drug resistance should allow treatment to be optimized, so that substantial improvements in the outlook for women with this disease can be achieved.     

Matrix metalloproteinases as emerging targets for cancer therapy

The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that play a key role in connective tissue-remodeling proceses. The expression and activity of these proteolytic enzymes is highly regulated by growth factors, cytokines, and hormones, as well as by interactions with specific tissue inhibitors of metalloproteinases (TIMPs). These enzymes are frequently overexpressed in many tumors, and in some cases it has been demonstrated a correlation of high MMP levels with local recurrence and increased invasive and metastatic potential of different malignant tumors. Functional studies have provided evidence that MMPs play an important role in the proteolytic destruction of extracellular matrix and basement membranes, thereby facilitating tumor invasion and metastasis. However, recent studies have indicated that MMPs may be also important in other steps of tumor evolution including neoplastic cell proliferation and angiogenesis stimulation at primary and metastatic sites. Based on the functional relevance of MMPs in tumor progression and metastasis, a number of inhibitors have been developed to try to block the activity of these enzymes. Clinical studies currently in progress will contribute to clarify whether these protease inhibitors may be part of future therapeutic strategies to control the metastatic capacity of neoplastic cells.     

Multimodal treatment strategies for elderly patients with head and neck cancer

The population in developed countries is growing older and the number of elderly people annually diagnosed with head and neck cancers is expected to rapidly increase within the following decades, since these types of tumors are age-dependent. The vast majority of older head and neck cancer patients present with locally advanced disease and multimodality treatment, including surgery, radiation and/or chemotherapy, is considered the best therapeutic option for these patients. However, several factors, including comorbidities, disabilities, frailty, and impaired functional status are considered to be more relevant criteria than chronological age per se for treatment planning. Therapeutic decisions are often complicated and demand the participation of many specialists. Advances in surgical and radiation techniques, along with the use of conventional chemotherapy and molecularly targeted agents, have improved treatment outcomes. The best-tailored individualized therapeutic option should be selected for these patients in order to avoid high toxicity and major functional deterioration. Still, more older-specific studies are needed in order to produce more definitive and applicable results. The aim of this review article is to investigate the multimodal treatment approaches for elderly patients with head and neck cancer.     

New approaches in systemic treatment of advanced colorectal cancer: the molecular targets era

The prognosis of advanced colorectal cancer remains poor in spite of the advances obtained in recent years with new therapeutic agents, new approaches in surgical procedures and new diagnostic methods. New treatments directed to molecular targets have emerged and are being developed to improve these results, but there is a need to optimize and define the best use of these new approaches. In this review, the authors examine the most important trials with monoclonal antibodies and tyrosine kinase inhibitors in the treatment of advanced colorectal cancer.     

Physical exercise for cancer patients with advanced disease: a randomized controlled trial

Background.

Physical exercise can improve cancer patients'' functioning and reduce their symptom levels. A randomized, controlled trial was launched to test the hypothesis that physical exercise reduces fatigue and improves physical performance in cancer patients with advanced and incurable disease.

Methods.

Cancer patients (n = 231) with a life expectancy ≤2 years were randomized to a physical exercise group (PEG, n = 121) or a control usual care group (UCG, n = 110). The PEG exercised under supervision 60 minutes twice a week for 8 weeks. Assessments were performed before and after the intervention. The primary outcome was physical fatigue (PF) measured by the Fatigue Questionnaire. Physical performance was a secondary outcome measured by the Shuttle Walk Test (SWT) and hand grip strength (HGS) test. Analyses were performed after multiple imputations for missing data. The trial is registered with ClinicalTrials.gov (identifier, {"type":"clinical-trial","attrs":{"text":"NCT00397774","term_id":"NCT00397774"}}NCT00397774).

Findings.

Thirty-six percent of the PEG were lost to follow-up compared with 23% of the UCG, primarily as a result of disease progression. Seventy-eight PEG and 85 UCG patients completed the intervention. Analyses showed no significant between-group effects in PF. However, clinically and statistically significant between-group effects were found for the SWT and HGS test.

Interpretation.

Fatigue was not reduced but physical performance (SWT and HGS test) was significantly improved after 8 weeks of physical exercise. Physical exercise might therefore be a suitable approach for maintaining physical capacity in cancer patients with incurable and advanced disease.     

New approaches in systemic treatment of advanced colorectal cancer: the molecular targets era

The prognosis of advanced colorectal cancer remains poor in spite of the advances obtained in recent years with new therapeutic agents, new approaches in surgical procedures and new diagnostic methods. New treatments directed to molecular targets have emerged and are being developed to improve these results, but there is a need to optimize and define the best use of these new approaches. In this review, the authors examine the most important trials with monoclonal antibodies and tyrosine kinase inhibitors in the treatment of advanced colorectal cancer.