Journal of Experimental & Clinical Cancer Research 

About: Journal of Experimental & Clinical Cancer Research is an academic journal published by Springer Science+Business Media. The journal publishes majorly in the area(s): Cancer research & Medicine. It has an ISSN identifier of 1756-9966. It is also open access. Over the lifetime, 4614 publications have been published receiving 143223 citations. The journal is also known as: Journal of experimental and clinical cancer research.

Apoptosis in cancer: from pathogenesis to treatment

Abstract: Apoptosis is an ordered and orchestrated cellular process that occurs in physiological and pathological conditions. It is also one of the most studied topics among cell biologists. An understanding of the underlying mechanism of apoptosis is important as it plays a pivotal role in the pathogenesis of many diseases. In some, the problem is due to too much apoptosis, such as in the case of degenerative diseases while in others, too little apoptosis is the culprit. Cancer is one of the scenarios where too little apoptosis occurs, resulting in malignant cells that will not die. The mechanism of apoptosis is complex and involves many pathways. Defects can occur at any point along these pathways, leading to malignant transformation of the affected cells, tumour metastasis and resistance to anticancer drugs. Despite being the cause of problem, apoptosis plays an important role in the treatment of cancer as it is a popular target of many treatment strategies. The abundance of literature suggests that targeting apoptosis in cancer is feasible. However, many troubling questions arise with the use of new drugs or treatment strategies that are designed to enhance apoptosis and critical tests must be passed before they can be used safely in human subjects.

Health-related quality of life in breast cancer patients: A bibliographic review of the literature from 1974 to 2007

Abstract: Quality of life in patients with breast cancer is an important outcome. This paper presents an extensive overview on the topic ranging from descriptive findings to clinical trials. This was a bibliographic review of the literature covering all full publications that appeared in English language biomedical journals between 1974 and 2007. The search strategy included a combination of key words 'quality of life' and 'breast cancer' or 'breast carcinoma' in titles. A total of 971 citations were identified and after exclusion of duplicates, the abstracts of 606 citations were reviewed. Of these, meetings abstracts, editorials, brief commentaries, letters, errata and dissertation abstracts and papers that appeared online and were indexed ahead of publication were also excluded. The remaining 477 papers were examined. The major findings are summarized and presented under several headings: instruments used, validation studies, measurement issues, surgical treatment, systemic therapies, quality of life as predictor of survival, psychological distress, supportive care, symptoms and sexual functioning. Instruments-Several valid instruments were used to measure quality of life in breast cancer patients. The European Organization for Research and Treatment of Cancer Core Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and its breast cancer specific complementary measure (EORTC QLQ-BR23) and the Functional Assessment Chronic Illness Therapy General questionnaire (FACIT-G) and its breast cancer module (FACIT-B) were found to be the most common and well developed instruments to measure quality of life in breast cancer patients. Surgery-different surgical procedures led to relatively similar results in terms of quality of life assessments, although mastectomy patients compared to conserving surgery patients usually reported a lower body image and sexual functioning. Systemic therapies-almost all studies indicated that breast cancer patients receiving chemotherapy might experience several side-effects and symptoms that negatively affect their quality of life. Adjuvant hormonal therapies also were found to have similar negative impact on quality of life, although in general they were associated with improved survival. Quality of life as predictor of survival-similar to known medical factors, quality of life data in metastatic breast cancer patients was found to be prognostic and predictive of survival time. Psychological distress-anxiety and depression were found to be common among breast cancer patients even years after the disease diagnosis and treatment. Psychological factors also were found to predict subsequent quality of life or even overall survival in breast cancer patients. Supportive care-clinical treatments to control emesis, or interventions such as counseling, providing social support and exercise could improve quality of life. Symptoms-Pain, fatigue, arm morbidity and postmenopausal symptoms were among the most common symptoms reported by breast cancer patients. As recommended, recognition and management of these symptoms is an important issue since such symptoms impair health-related quality of life. Sexual functioning-breast cancer patients especially younger patients suffer from poor sexual functioning that negatively affect quality of life. There was quite an extensive body of the literature on quality of life in breast cancer patients. These papers have made a considerable contribution to improving breast cancer care, although their exact benefit was hard to define. However, quality of life data provided scientific evidence for clinical decision-making and conveyed helpful information concerning breast cancer patients' experiences during the course of the disease diagnosis, treatment, disease-free survival time, and recurrences; otherwise finding patient-centered solutions for evidence-based selection of optimal treatments, psychosocial interventions, patient-physician communications, allocation of resources, and indicating research priorities were impossible. It seems that more qualitative research is needed for a better understanding of the topic. In addition, issues related to the disease, its treatment side effects and symptoms, and sexual functioning should receive more attention when studying quality of life in breast cancer patients.

Combination of CTLA-4 and PD-1 blockers for treatment of cancer

Abstract: Targeting checkpoints of immune cell activation has been demonstrated to be the most effective approach for activation of anti-tumor immune responses. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1), both inhibitory checkpoints commonly seen on activated T-cells have been found to be the most reliable targets for the treatment of cancer. Six drugs targeting PD-1 or its ligand PD-L1 and one drug targeting CTLA-4 have been approved for treatment of different types of cancers and several others are in advanced stages of development. The drugs when administered as monotherapy had dramatic increase in durable response rates and had manageable safety profile, but more than 50% of patients failed to respond to treatment. Combination of CTLA-4 and PD-1 blockers was then evaluated to increase the response rates in patients, and ipilimumab (anti-CTLA-4) plus nivolumab (anti-PD-1) combination was shown to significantly enhance efficacy in metastatic melanoma patients. Subsequently, ipilimumab plus nivolumab was approved for treatment of metastatic melanoma, advanced renal cell carcinoma and metastatic colorectal cancer with MMR/MSI-H aberrations. The success of combination encouraged multiple clinical studies in other cancer types. Efficacy of the combination has been shown in a number of published studies and is under evaluation in multiple ongoing studies. This review aims to support future research in combination immunotherapy by discussing the basic details of CTLA-4 and PD-1 pathways and the results from clinical studies that evaluated combination of CTLA-4 and PD-1/PD-L1 blockers.

The role of cellular reactive oxygen species in cancer chemotherapy

Abstract: Most chemotherapeutics elevate intracellular levels of reactive oxygen species (ROS), and many can alter redox-homeostasis of cancer cells. It is widely accepted that the anticancer effect of these chemotherapeutics is due to the induction of oxidative stress and ROS-mediated cell injury in cancer. However, various new therapeutic approaches targeting intracellular ROS levels have yielded mixed results. Since it is impossible to quantitatively detect dynamic ROS levels in tumors during and after chemotherapy in clinical settings, it is of increasing interest to apply mathematical modeling techniques to predict ROS levels for understanding complex tumor biology during chemotherapy. This review outlines the current understanding of the role of ROS in cancer cells during carcinogenesis and during chemotherapy, provides a critical analysis of the methods used for quantitative ROS detection and discusses the application of mathematical modeling in predicting treatment responses. Finally, we provide insights on and perspectives for future development of effective therapeutic ROS-inducing anticancer agents or antioxidants for cancer treatment.

Metabolic reprogramming: the emerging concept and associated therapeutic strategies

Abstract: Tumor tissue is composed of cancer cells and surrounding stromal cells with diverse genetic/epigenetic backgrounds, a situation known as intra-tumoral heterogeneity. Cancer cells are surrounded by a totally different microenvironment than that of normal cells; consequently, tumor cells must exhibit rapidly adaptive responses to hypoxia and hypo-nutrient conditions. This phenomenon of changes of tumor cellular bioenergetics, called “metabolic reprogramming”, has been recognized as one of 10 hallmarks of cancer. Metabolic reprogramming is required for both malignant transformation and tumor development, including invasion and metastasis. Although the Warburg effect has been widely accepted as a common feature of metabolic reprogramming, accumulating evidence has revealed that tumor cells depend on mitochondrial metabolism as well as aerobic glycolysis. Remarkably, cancer-associated fibroblasts in tumor stroma tend to activate both glycolysis and autophagy in contrast to neighboring cancer cells, which leads to a reverse Warburg effect. Heterogeneity of monocarboxylate transporter expression reflects cellular metabolic heterogeneity with respect to the production and uptake of lactate. In tumor tissue, metabolic heterogeneity induces metabolic symbiosis, which is responsible for adaptation to drastic changes in the nutrient microenvironment resulting from chemotherapy. In addition, metabolic heterogeneity is responsible for the failure to induce the same therapeutic effect against cancer cells as a whole. In particular, cancer stem cells exhibit several biological features responsible for resistance to conventional anti-tumor therapies. Consequently, cancer stem cells tend to form minimal residual disease after chemotherapy and exhibit metastatic potential with additional metabolic reprogramming. This type of altered metabolic reprogramming leads to adaptive/acquired resistance to anti-tumor therapy. Collectively, complex and dynamic metabolic reprogramming should be regarded as a reflection of the “robustness” of tumor cells against unfavorable conditions. This review focuses on the concept of metabolic reprogramming in heterogeneous tumor tissue, and further emphasizes the importance of developing novel therapeutic strategies based on drug repositioning.