Reviews & Analysis

Viruses have been used for cancer treatment for over a century. From the early clinical studies with various wild-type viruses, to the modern trials with engineered viruses, virotherapy has emerged as a promising therapeutic strategy. The authors discuss the progress and challenges associated with oncolytic virotherapeutic agents, summarizing the data from clinical reports, and the implications of this data for future virotherapy development.

Therapy that effectively shrinks tumor bulk is often unable to completely eliminate disease. One theory is that chemotherapeutic agents target rapidly growing cells, but can leave a pool of slowly proliferating, quiescent cells (stem cells) unharmed. These cells can then divide and reestablish the tumor once therapy ceases. This Viewpoint presents evidence that gastric cancer stem cells could originate from bone marrow.

This article describes the case of a 78-year-old man who was presented with a rapidly growing mass in the left axilla but no other symptoms. Excisional biopsy of the mass revealed a primary adenocarcinoma with apocrine features. The patient underwent dissection of the left axillary lymph node and received radiation therapy. Fifteen months later, a biopsy revealed metastatic apocrine carcinoma. The authors discuss the differential diagnosis and treatment options for patients with apocrine carcinoma, a rare subtype of sweat-gland carcinoma.

The presence of tumor cells in the bone marrow of primary breast cancer patients at surgery has been shown to be an independent prognostic indicator of relapse. Studies are underway to improve methods of detection, such as immunobead enrichment and real-time RT-PCR. This article reviews the current methodologies and technical improvements that are being investigated, and the authors discuss the major hurdles that should be overcome before analysis of minimal residual disease to predict prognosis can become standard practice in the clinical setting.

Many women with ovarian cancer undergo both surgery and chemotherapy and because the majority of women will eventually experience recurrent disease, it is important to recognize how such treatments may disrupt patient quality of life. The authors of this review discuss the quality of life issues, and emphasize the importance of developing further strategies to identify women at risk of serious quality of life disruption so that effective interventions can be designed.

Bisphosphonates are used for skeletal protection in osteoporosis, cancer bone metastasis, multiple myeloma, and Paget's disease of the bone; however, these drugs also have the potential for causing a number of adverse effects. While these do not limit bisphosphonate use, the incidence of these adverse events can be minimized if appropriate care is taken with their administration, and by maintaining appropriate surveillance and patient care, as discussed in this review.

Older patients are less likely to receive standard treatments for cancer than similar younger patients. Arti Hurria proposes a specific oncology geriatric assessment, including functional status, comorbid medical conditions, nutritional status, cognitive function, psychological state and social support, and medication review, to pinpoint an individual's functional age and facilitate appropriate care.

Post-therapy prostate-specific antigen (PSA) changes have been associated with improved survival in castrate metastatic patients, but currently no drug has been approved strictly on the basis of a post-treatment decline in PSA, as it is unproven that such PSA changes are surrogates for true clinical benefits. Fleming and coauthors address the critical question of whether PSA post-therapy decline reflects true clinical benefit, and if it should be used as an intermediate endpoint for accelerated approval. The authors emphasize the importance of recognizing that there are a range of clinical benefits to patients that can favorably improve the quality and possibly the duration of survival independent of PSA.

Experimental data indicate that lymphodepletion prior to adoptive transfer of tumor specific T-lymphocytes plays a key role in enhancing treatment efficacy by eliminating regulatory T-cells and competing elements of the immune system. Newly emerging animal data suggest that more profound lymphoablative conditioning with autologous hematopoetic stem-cell rescue might further enhance treatment results. The authors review the recent advances in adoptive immunotherapy of solid tumors and discuss the rationale for lymphodepleting conditioning, and also address the safety issues of translating experimental animal results of total lymphoid ablation into clinical practice.

Vascular disrupting agents (VDAs) are designed to disrupt the already established abnormal vasculature, and induce rapid shutdown of tumor blood supply causing subsequent tumor death from hypoxia and nutrient deprivation. The authors discuss the strategies to improve drug delivery, and suggest that further clinical trials need to evaluate novel treatment strategies that combine VDAs with radiotherapy, cytotoxic drugs, anti-angiogenic agents, and other novel targeted therapies. Close attention to the cardiovascular side effect profile of these agents is also imperative during their clinical development.

Cancer incidence and mortality are expected to rise substantially in low-income countries. Franco Cavalli outlines how we should react to this threat, and gives guidance on preventive measures that can be tailored to different resource settings.

Surgery and chemotherapy form the cornerstone in the treatment of ovarian cancer. The standard of care for primary ovarian cancer is platinum and taxane-based chemotherapy. Despite the favorable response characteristics, however, most women with advanced-stage ovarian cancer will relapse. Herzog and Pothuri discuss the treatment options available and highlight the issues surrounding how these patients should be managed with surgical, chemotherapy, biological targeted agents and radiation therapy.

Adjuvant chemotherapy improves survival for patients with early-stage disease but this benefit is not equal for all patients. Molecular characteristics of the cancer affect sensitivity to chemotherapy. In general, estrogen receptor (ER)-negative disease is more sensitive to chemotherapy than ER-positive tumors. Before any new molecular classification (or predictive test) is adopted for routine clinical use, however, several criteria need to be met. This review describes the current limitations and future promises of gene-expression-based molecular classification of breast cancer and how it might impact selection of adjuvant therapy for individual patients.

It is unclear whether stressful life events, work-related stress, or perceived global stress are differentially associated with breast cancer incidence and breast cancer relapse in prospective studies. In this review systematic and explicit methods were used to identify, select, and critically appraise relevant studies. Despite the heterogeneity in the results obtained, the authors conclude that stress does not seem to increase the risk of breast cancer incidence but emphasize that larger studies on stress and breast cancer relapse are required to determine if stress affects the progression of breast cancer.

The dilemma for those managing patients with cancer and neutropenia is whether the potential benefit of fluoroquinolones outweigh their disadvantages—drug resistance, toxicity and cost. The authors of this Viewpoint re-examine the question of who (if anyone) should receive fluoroquinolone prophylaxis.

The development of the 70-gene prognosis signature for breast cancer was evaluated in the MINDACT (Microarray In Node negative Disease may Avoid ChemoTherapy) trial to assess the clinical relevance of the 70-gene prognosis signature, and how this compares with traditional prognostic factors for assigning adjuvant chemotherapy for patients with node-negative breast cancer. This review outlines the background work and rationale behind the final design of the MINDACT trial and how these considerations can help to optimize future trials and aim to improve individualization of cancer therapy.

Owing to cardiovascular and thromboembolic toxicities, oral estrogens were abandoned as treatments for prostate carcinoma; however, it is now recognized much of this toxicity can be avoided by parenteral (intramuscular or transdermal) estrogen administration. Ockrim and coauthors highlight the cost and protective andropause advantages of estrogen therapy, advocating a re-evaluation of this promising, but forgotten therapy.