Chemical biology articles within Nature Reviews Clinical Oncology

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  • Perspective |

    A systems biology-based approach incorporating multiscale, longitudinal measurements (from single-cell analyses to whole-body monitoring) would help to decipher the complexity of cancer and would facilitate the development of personalized therapies. The authors of this Perspective discuss how systems biology-based approaches can provide data for early detection of disease transitions, prediction of therapeutic responses and clinical outcomes, and for the design of personalized treatments.

    • James T. Yurkovich
    • , Qiang Tian
    •  & Leroy Hood

  • Perspective |

    Precision medicine approaches to the treatment of cancer are largely reliant on genomic analysis alone. In this Perspective the authors provide a rationale for the incorporation of analysis of the proteome, which is a rich source of biological heterogeneity, into the treatment and management of patients with cancer.

    • Bing Zhang
    • , Jeffrey R. Whiteaker
    •  & Amanda G. Paulovich

  • News & Views |

    PapSEEK, a novel liquid-based cytology test, enabled the highly specific detection of endometrial and ovarian cancer in a retrospective study. Herein, I discuss potential applications of this tool, both for cancer screening of asymptomatic populations and for the early diagnosis of cancer in symptomatic women.

    • Usha Menon

  • Review Article |

    The development of cancer involves several epigenomic alterations, and the presence of certain alterations before the development of cancer is associated with cancer risk. In this Review, the authors describe the potential of epigenomics-based assays to predict an individual's risk of cancer, including discussions of technical, practical and societal issues regarding the implementation of such assays.

    • Martin Widschwendter
    • , Allison Jones
    •  & Nora Pashayan

  • Comment |

    Experimental research on cancer-associated cachexia is advancing at an accelerated pace while knowledge of the complex underlying biology of cachexia in humans lags behind. An unmet need exists to accelerate the identification of causal mechanisms in patients with cancer and to determine the parallels between experimental systems and distinct isotypes of human cachexia.

    • Vickie E. Baracos

  • Review Article |

    The PARP inhibitor olaparib has been approved for clinical use in patients with ovarian cancer withBRCA 1/2 mutations; however, this agent, which can confer substantial improvements in patient survival might also be effective in those without a BRCA mutation. Here, the authors describe the potential for expanding the use of BRCA-mutation testing and PARP inhibition beyond those who are likely to have a BRCAmutation.

    • Angela George
    • , Stan Kaye
    •  & Susana Banerjee

  • Review Article |

    Tyrosine kinase inhibitors (TKIs) are the most common agents used for the treatment of patients with chronic myeloid leukaemia (CML). Several agents are available for frontline treatment, or after the development of resistance or intolerance to agents previously used. Herein, the authors evaluate differences between available TKIs, and discuss several end points that can be considered when selecting the first and subsequent lines of treatment of patients with CML.

    • Gianantonio Rosti
    • , Fausto Castagnetti
    •  & Michele Baccarani

  • Review Article |

    Agents targeting the PI3K/AKT/mTOR pathway have been shown to be safe and effective in treating a number of tumour types. This Review outlines the background to these inhibitors and discusses the second-generation inhibitors of this pathway. The authors propose that the way forward for the development of inhibitors of the PI3K/AKT/mTOR pathway might be a systems biology approach and biomarker-driven studies.

    • Jordi Rodon
    • , Rodrigo Dienstmann
    •  & Josep Tabernero

  • News & Views |

    The small EVEREST trial has shown that the concept of guiding cetuximab dose escalation using the clinical parameter of acneiform skin rash is safe. However, as no significant increase of cetuximab efficacy could be observed, data from the ongoing EVEREST II trial must be awaited before dose escalation can be considered for clinical use.

    • Sebastian Stintzing
    •  & Heinz-Josef Lenz

  • Review Article |

    Despite the advent of HER2-directed therapies, many patients with HER2-positive early stage breast cancer relapse and die of this disease. Trials to define, refine and optimize the use of the approved HER2-targeted agents are ongoing. New approaches are being developed and a series of large trials in the adjuvant and neoadjuvant settings are planned or in progress. In this Review, Arteaga et al. describe the current treatment for HER2-positive breast cancer and provide an update on ongoing clinical trials and translational research.

    • Carlos L. Arteaga
    • , Mark X. Sliwkowski
    •  & Luca Gianni

  • Opinion |

    The use of therapy that is truly targeted to the needs and biological requirements of an individual patient is an aim for many in the oncology field. Jackson and Sood discuss the implications of targeted therapies on patients and the health-care system and discuss methods that might be used to maximize efficiency, cost effectiveness and patient survival.

    • David B. Jackson
    •  & Anil K. Sood

  • News & Views |

    Despite the improved progression-free survival and overall survival demonstrated by cisplatin–gemcitabine chemoradiation in a phase III randomized trial in patients with stage IIB to IVA cervical cancer, the acute and chronic toxic effects urge caution before embracing this as a new treatment paradigm.

    • Peter G. Rose

  • Review Article |

    The translation of mRNA is a tightly regulated process that is necessary for protein synthesis, and dysregulation of this process is associated with the development and progression of cancers. This Review highlights the components of translation machinery and how alterations in these proteins and their principle upstream signaling pathways can impact on cancer. Drugs that are currently being developed to target the translational machinery are also discussed.

    • Sarah P. Blagden
    •  & Anne E. Willis

  • News & Views |

    An important phase III trial involving transplant-eligible patients with multiple myeloma compared bortezomib and dexamethasone (BzD) induction with the previous standard of care. BzD was associated with a higher overall response and a deeper response to therapy that translated to superior responses following high-dose therapy and autologous stem cell transplantation.

    • Jacob Laubach
    •  & Paul Richardson

  • News & Views |

    A randomized phase III trial of patients with stage II and III colon cancer showed no benefit of adding bevacizumab to standard adjuvant oxaliplatin plus fluorouracil and leucovorin. Despite suggestive evidence of a short-term benefit, these data and other similar findings dictate that adjuvant bevacizumab should not be used in colon cancer.

    • Daniel J. Sargent

  • News & Views |

    Palumbo and coauthors report on the results of a randomized trial comparing two doses of melphalan in patients with symptomatic multiple myeloma. Overall complete response rates, median progression-free survival and projected 5-year overall survival were significantly higher among patients receiving the higher melphalan dose. These results confirm that for this patient population melphalan 200 mg/m2 should remain the gold standard conditioning regimen.

    • Sergio Giralt

  • News & Views |

    Ongoing investigation into the use of thalidomide in the treatment of multiple myeloma has demonstrated efficacy as a combination treatment during induction and as maintenance therapy. Thalidomide–doxorubicin–dexamethasone combination therapy improved response rate; however, the development of drug resistance remains a concern.

    • Antonio Palumbo

  • News & Views |

    A phase III trial investigated the efficacy of carboplatin and a taxane with and without cetuximab, a monoclonal antibody against EGFR, in patients with advanced non-small-cell lung cancer. This trial did not reveal an improvement in the primary end point of progression-free survival (according to an independent radiological review committee) with the addition of cetuximab to the carboplatin and taxane regimen. A retrospective investigation of potential biomarkers did not reveal any significant association between these biomarkers and cetuximab efficacy.

    • Thomas E. Stinchcombe
    •  & Mark A. Socinski

  • News & Views |

    Encouraging data have been reported from a randomized, double-blind, phase III trial comparing pazopanib therapy to placebo in treatment-naive and cytokine-refractory patients with advanced renal-cell carcinoma. The challenge that lies ahead is determining where pazopanib fits into the crowded therapeutic algorithms for this disease.

    • Sumanta Kumar Pal
    •  & Robert A. Figlin

  • Review Article |

    The use of azanucleosides has altered the treatment paradigm of myelodysplastic syndromes. Recently, treatment with 5-azacitidine was demonstrated to prolong survival in patients with myelodysplastic syndromes for the first time. This Review discusses the potential of these forms of treatment as monotherapy and in combination, and assesses the most recent clinical data.

    • Alfonso Quintás-Cardama
    • , Fabio P. S. Santos
    •  & Guillermo Garcia-Manero

  • Review Article |

    EGFR is one of the most studied targets in oncology, and several inhibitors have shown promising results in selected patient populations. However, intrinsic and acquired resistance to these targeted therapies is increasingly recognized. The authors of this Review describe the successful translation of EGFR inhibitors to the clinic, and highlight the mechanisms of resistance to these agents that limit their long-term efficacy. Understanding these processes will allow researchers to develop therapies that overcome resistance and ultimately lead to more successful outcomes.

    • Deric L. Wheeler
    • , Emily F. Dunn
    •  & Paul M. Harari

  • Review Article |

    Metronomic chemotherapy is the chronic administration of chemotherapeutic agents at relatively low, minimally toxic doses, and with no prolonged drug-free breaks. This type of chemotherapy inhibits tumor growth primarily through anti-angiogenic mechanisms. The latest clinical trials of metronomic chemotherapy in adult and pediatric cancer patients are discussed and the authors highlight the research efforts that need to be made to facilitate the optimal development of metronomic chemotherapy in the clinic.

    • Eddy Pasquier
    • , Maria Kavallaris
    •  & Nicolas André

  • News & Views |

    Imatinib 400 mg has been the first-line therapy for chronic myeloid leukemia (CML) since 2001 but may have been licensed at too low a dose. A recent study compared the standard dose with higher doses in patients with newly diagnosed CML and found no difference in response rates at 12 months. But, is the devil in the detail?

    • Jane F. Apperley

  • News & Views |

    Although high-dose methotrexate is widely accepted as the most effective chemotherapeutic agent for primary CNS lymphoma, no optimal dose or dosing strategy has been established. Researchers from the International Extranodal Lymphoma Study Group used clinical trial data to explore whether or not an area under the curve model might be useful to optimize methotrexate dosing. The results strongly suggest that effective methotrexate dose is an important variable in patient outcome.

    • Lauren E. Abrey

  • Case Study |

    A 63-year-old male patient under chronic treatment with sorafenib for an unresectable multifocal hepatocellular carcinoma (HCC) presented with suspected variant angina. Spontaneous spasm occurred during cardiac catheterization and was revealed during coronary angiogram with the unusual feature of a retrograde transient filling of a contralateral branch. Italo Porto and colleagues contend that the effects of sorafenib treatment were primarily responsible for the major cardiovascular event observed in this case, and suggest that clinicians should be aware of this possible severe complication of sorafenib therapy.

    • Italo Porto
    • , Andrea Leo
    •  & Filippo Crea

  • News & Views |

    Dose-dense administration of paclitaxel as well as intraperitoneal administration of platinum and paclitaxel as first-line treatments provide similar advantages compared with standard treatment in advanced ovarian cancer. Both approaches, however, need to be confirmed by additional studies. A low dose of pegylated liposomal doxorubicin combined with carboplatin is superior to standard paclitaxel and carboplatin in relapsed platinum-sensitive ovarian cancer.

    • Thomas Hogberg

  • Review Article |

    The first generation of anti-cancer agents using novel nanomaterials has successfully entered widespread use and newer nanomaterials are gaining increasing interest as potential multifunctional therapeutic agents. The authors of this Review discuss how the new features of these agents could potentially allow increased cancer selectivity, changes in pharmacokinetics, amplification of cytotoxic effects, and simultaneous imaging capabilities.

    • David A. Scheinberg
    • , Carlos H. Villa
    •  & Michael R. McDevitt

  • Review Article |

    Mammalian target of rapamycin (mTOR) has a key role in several pathways that are involved in cell growth and cancer. In this Review, Dr. Dancey outlines the mechanisms of action and performance of current mTOR inhibitors in clinical trials. Second-generation inhibitors are also discussed along with strategies that should be used to improve outcomes achieved with mTOR inhibitors.

    • Janet Dancey

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