Immunotherapy for colorectal cancer: where are we heading?

Introduction: In the last few years, significant advances in molecular biology have provided new therapeutic options for colorectal cancer (CRC). The development of new drugs that target the immune response to cancer cells seems very promising and has already been established for other tumor types. In particular, the use of immune checkpoint inhibitors seems to be an encouraging immunotherapeutic strategy.

Areas covered: In this review, the authors provide an update of the current evidence related to this topic, though most immunotherapies are still in early-phase clinical trials for CRC. To understand the key role of immunotherapy in CRC, the authors discuss the delicate balance between immune-stimulating and immune-suppressive networks that occur in the tumor microenvironment.

Expert opinion: Modulation of the immune system through checkpoint inhibition is an emerging approach in CRC therapy. Nevertheless, selection criteria that could enable the identification of patients who may benefit from these agents are necessary. Furthermore, potential prognostic and predictive immune biomarkers based on immune and molecular classifications have been proposed. As expected, additional studies are required to develop biomarkers, effective therapeutic strategies and novel combinations to overcome immune escape resistance and enhance effector response.     

Antibody therapeutics for treating prostate cancer: where are we now and what comes next?

Introduction: Progress in the understanding of molecular events of carcinogenesis and cancer evolution as well as the identification of tumor antigens has led to the development of different targeted therapeutic approaches, including the use of monoclonal antibodies (mAbs). Prostate cancer (PC) is highly amenable to mAb targeting given the existence of prostate-specific targets and the natural history and localization of metastatic disease.

Areas covered: Several aspects of the PC phenotype, including growth factors, angiogenesis mediators, bone microenvironment signals, and immune evasion pathways, have become areas of ongoing investigation in terms of mAb targeting. These are reviewed. The greatest success so far has been the development of mAbs against prostate-specific tumor antigen (PSMA), which opened an opportunity to improve diagnostic accuracy and simultaneously target metastatic disease.

Expert opinion: As mAb use in PC continues to evolve, more accurate imaging of the extent of disease and more effective mAb therapies (naked or conjugated with drugs, toxins or radioactive molecules) are emerging. In addition, the combination of mAbs with other treatment modalities is expected to further improve responses and overall survival. Identification of validated biomarkers is necessary for better recognition of patient subgroups who will derive the greatest benefit from mAb therapy.     

Immunotherapy and immunoprevention of cancer: where do we stand?

Although evolution has shaped the immune system to control microbial invasions, this does not necessarily mean that the immune system can not be triggered to eliminate tumour cells. The exploitation of the terrific potential of the immune system to recognise cell alterations and to selectively destroy large populations of neoplastic cells is a possibility made even more attractive by the advances in our understanding of the immune mechanisms and our ability to manipulate them. This review summarises the state of the different immunotherapy strategies available or in development today, and examines the future developments that hold out the promise of an effective control of cancer growth.     

Immunotherapy and immunoprevention of cancer: where do we stand?

Although evolution has shaped the immune system to control microbial in-vasions, this does not necessarily mean that the immune system can not be triggered to eliminate tumour cells. The exploitation of the terrific potential of the immune system to recognise cell alterations and to selectively destroy large populations of neoplastic cells is a possibility made even more attractive by the advances in our understanding of the immune mechanisms and our ability to manipulate them. This review summarises the state of the different immunotherapy strategies available or in development today, and examines the future developments that hold out the promise of an effective control of cancer growth.     

Surgery and cancer promotion: are we trading beauty for cancer?

It is well-known that cancer surgery can actually promote the growth of some tumors by a variety of mechanisms. There are observational data suggesting that surgery per se can increase the risk of cancer among individuals without a history of clinical cancer. Occult microscopic cancers are exceedingly common in the general population and are held in a dormant state by a balance between cell proliferation and cell death and also an intact host immune surveillance. The catecholamine surge from the stress of surgery and resulting β(2)-adrenergic signaling culminates in a transient and robust increased vascular endothelial growth factor expression locally and systemically that is enough to start tumor angiogenesis and end dormancy. The same catecholamine surge and β(2)-adrenergic signaling impairs cell-mediated immunity at a crucial time. Elegant animal studies have demonstrated that perioperative nonselective β-blockade abrogates surgical stress-induced angiogenesis and tumor growth. Prospective human trials are desperately needed and clinical implications are discussed.     

Physiatrist 2007: who are we and where are we going?

The field of physical medicine and rehabilitation has evolved greatly over the last half century. Although practice patterns continue to change, the unifying concepts of physiatry remain the same. Awareness of the unique aspects of physiatry is still not optimal. It is incumbent on the physiatric community to educate our colleagues, our patients, and the public about our unique field.     

Drug development for Alzheimer's disease: Where are we now and where are we headed?

Objective: The aim of this article was to provide a survey of the clinical development of pharmacotherapy for Alzheimer's disease (AD).Methods: A search of PubMed to identify pertinent English-language literature was conducted using the terms Alzheimer's disease AND clinical trials (2003–2008), dementia AND prevention AND clinical trials (2003–2008), and the chemical names of all compounds mentioned in articles on new drugs for AD published since 2005. www.ClinicalTrials.gov was searched for relevant trials. Abstracts of the 2008 International Conference on Alzheimer's Disease (ICAD) were reviewed for relevance, as were pharmaceutical company and AD advocacy Web sites. Articles selected for review were primary reports of data from preclinical studies and clinical trials.Results: A large number of drugs with differing targets and mechanisms of action are under development for the treatment of AD. Phase III trials of Ginkgo biloba, NSAIDs, phenserine, statins, tarenflurbil, tramiprosate, and xaliproden have been completed, none of them demonstrating adequate efficacy. Encouraging results from completed Phase II trials of dimebon, huperzine A, intravenous immunoglobulin, and methylthioninium chloride were reported at ICAD 2008. Nineteen compounds are currently in Phase II trials, and 3 compounds (AN1792, lecozotan SR, and SGS742) failed at this stage of development.Conclusions: Despite disappointing results from recently completed Phase III trials of several novel compounds, the extent and breadth of activity at all phases of clinical development suggest that new pharmacotherapeutic options for the treatment of AD will become available within the next decade.     

Treating hematological malignancies with cell therapy: where are we now?

Introduction: Adoptive cell therapy (ACT) is becoming an increasingly successful and widespread form of treatment for different types of cancer. Compared to chemotherapy or monoclonal antibodies, ACT is an active biological strategy, with infused immune cells featuring dynamic migration, expansion and long-term persistence properties. ACT in hematological malignancies offered the initial proof of principle of the feasibility for this innovative ‘live-drug’.

Areas covered: In this review, the authors summarize the clinical results achieved with two specific strategies in hematological malignancies: chimeric antigen receptor (CAR) and T cell receptor (transgenic TCR) redirected T cells. Moreover, they discuss the recent pre-clinical studies aimed at increasing the feasibility, safety and efficacy of ACT.

Expert opinion: ACT can promote cancer regression in patients with leukemia, lymphoma and multiple myeloma. Nevertheless, more precise targeting of tumor cells and containment of side effects are needed. Overcoming tumor-associated immunosuppressive mechanisms and preventing tumor escape are also emerging as critical barriers. Finally, simplification in the manufacturing procedures should promote wider application of these technologies outside academic centers. Although the enthusiasm for ACT-based therapies is high, comprehensive and systematic clinical studies are required to advance the field.     

Compliance with hand hygiene guidelines: where are we in 2008?

OVERVIEW: It has long been known that hand hygiene among health care workers plays a central role in preventing the transmission of infectious agents. But despite a Joint Commission requirement that Centers for Disease Control and Prevention hand hygiene guidelines be implemented in hospitals, compliance among health care workers remains low. The authors argue that hospitals may best improve compliance by assessing the barriers to it, measuring the rates of compliance, educating staff on the importance of hand hygiene, making sanitizing products more available for staff use, and holding staff accountable. The authors emphasize as well that lasting improvement in hand hygiene is a collaborative effort that depends on the committed support of hospital administrators.