ABSTRACT
Postoperative asymptomatic patients with early cancer (lung cancer) have dormant disseminated tumor cells (DTCs) in their metastatic target organs, and the proliferation of these DTCs is the key link leading to clinical metastasis. The development of therapeutic agents to maintain DTCs dormant or eradicate dormant DTCs will prevent tumor metastasis and break through the bottleneck of improving the overall efficacy of treating malignant tumors. This paper reviews the methods of establishing in vitro and in vivo research models of DTCs with dormant characteristics to promote the understanding of dormant DTCs and improve the research and development efficiency of anti-tumor metastasis drugs.
ABSTRACT
Tumor dormancy refers to the status of disseminated cancer cells that remain in a viable yet not proliferating state for a prolonged period. Dormant cells will eventually "re-awake" resume their proliferation, and produce overt metastasis. The dormancy mechanism of cancer has attracted attention because of the close relationship between late recurrence and tumor dormancy. In this review, we illustrate the latest discoveries on the biological underpinnings of breast cancer dormancy and offer clinicians an overview of dormancy in breast cancer to guide them in the basic understanding of the complexity that underlies this process.
ABSTRACT
The prevention and treatment of tumor metastasis can significantly improve the survival of patients with solid tumors. However, there is still a lack of effective drugs for the prevention and treatment of metastasis. The main reason is that the existing intervention and therapeutic drugs are difficult to achieve precise prevention and treatment of metastasis. Due to disseminated tumor cells (DTCs) already exist in the metastatic target organs of early postoperative patients, they are difficult to be detected with existing imaging techniques, and there is a lack of effective intervention drugs and efficacy evaluation systems. When DTCs grow to be detectable by imaging, the patient is already in the advanced stage of cancer, which has become a bottleneck restricting the breakthroughs in metastasis prevention and treatment. This paper reviews the dormancy and survival mechanism of DTCs in metastatic target organs and its intervention strategies, in order to promote the curative effect of metastasis prevention and treatment.
ABSTRACT
Dormant follicular lymphoma, prostate carcinoma and breast carcinoma are frequently detected by autopsy of non-tumor patients. Dormancy of malignant cells in hematopoietic malignancies is associated with genesis, development and treatment of these diseases. Dormancy is the universally applied strategy by living organism during survival competition. As the in vivo neoplasm, tumor cells keep this property. Recently, much attention has been paid to the mechanisms of tumor dormancy. These studies not only have theoretical significance, provide new ways for the prevention and treatment of tumors, but also help the understanding of over-diagnosis, over-treatment and provide clues for precise medicine. This paper reviewed cellular mechanism of tumor cell dormancy,immunological and vascular regulation of dormant tumors. The clinical significance,application of these mechanisms and direction of further study, which will provide new clues for the treatment of hematopoietic malignancies, were also discussed.
ABSTRACT
BACKGROUND: Metronomics is defined by the combination of metronomic chemotherapy and drug repositioning. Since off‑patent chemotherapeutic drugs can be used and given the low toxicity profile of this approach, metronomics appears to be an invaluable alternative to bring affordable targeted therapies in low‑income countries. OBJECTIVE: The aim of this study was to report on the preliminary efficacy and safety of a metronomic vincristine/cyclophosphamide/methotrexate/ valproic acid regimen given to children with refractory cancer of various tumor types or with a very advanced disease. MATERIALS AND METHODS: This prospective, single‑center study evaluated the use of a metronomics protocol, consisting of a first cycle of weekly vincristine 1.5 mg/m2 (days: 1, 8, 15 and 22), daily cyclophosphamide 25 mg/m2 (days: 1‑21), twice weekly methotrexate 15 mg/m² (days: 21‑42) and daily valproic acid (30 mg/kg/d) followed by a 1‑week break. For the following cycles, vincristine was administrated only at week 1 and 5 of the cycle. This treatment was proposed to children with refractory disease and patients who were not eligible for the protocols available in the hospital. Adverse events were determined through laboratory analyses and investigator observations. RESULTS: From January 2010 to January 2011, 7 children (mean age: 5.4 ± 3 years old) were treated. Most frequent diagnosis was retinoblastoma. Two partial responses were observed in patients with neuroblastoma and retinoblastoma. These two patients are alive with stable disease at last follow‑up (6 and 26 months, respectively) after stopping treatment. CONCLUSION: Metronomics allows treating patients with advanced or refractory or relapsing disease and the introduction of targeted treatments in low‑income countries. The potential of metronomics in children and young adults living in middle‑ and low‑income countries warrants further larger studies.
Subject(s)
Administration, Metronomic , Adolescent , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Child, Preschool , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Developing Countries , Female , Humans , Male , Mali , Methotrexate/administration & dosage , Methotrexate/adverse effects , Neoplasms/drug therapy , Pilot Projects , Poverty , Valproic Acid/administration & dosage , Valproic Acid/adverse effects , Vincristine/administration & dosage , Vincristine/adverse effects , Young AdultABSTRACT
Tumor dormancy is a well-known clinical phenomenon and the underlying mechanisms are poorly understood.It has been speculated that one of the major factors accounting for the dormant behavior is impaired angiogenesis.As stimuli result in the imbalanced concentration between the pro-angiogenic factors and anti-angiogenic factors,the tumors would escape from dormancy.However,why a dormant(silent)tumor be-comes angiogenic has not been explained and the molecular events that participate in it are under investigation.Despite all that,anti-angiogenic therapy is a very promising strategy to induce tumor dormancy.