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Nature Reviews Clinical Oncology

Nature Reviews Clinical Oncology provides physicians and academics with authoritative and topical discussions of key developments in the field.


WIN to avoid the valley of death


The extraordinary scientific and technical advances in basic and translational cancer research, coupled with our increased knowledge of the nonmalignant and cancer genomes has changed our understanding of the multitude of diseases termed cancer, at every level: these advances include diagnosis, screening, prognosis, treatment, clinical

Targeted therapies: Defining the best-in-class in NSCLC


For patients with ALK-positive non-small-cell lung cancer (NSCLC) the standard first-line therapy is crizotinib. Resistance to first-line ALK inhibitors is common — inevitably, patients relapse, and can develop metastases in the central nervous system (CNS). The second-generation ALK inhibitor alectinib is able to penetrate the

Lung Cancer: Frontline nivolumab — CheckMate 026 ends in stalemate


The anti-PD-1 antibody nivolumab is an approved second-line therapy for advanced-stage non-small-cell lung cancer (NSCLC), but earlier use of this immunotherapeutic agent might be beneficial. In the phase III CheckMate 026 trial, David Carbone et al. addressed this question.The researchers randomly assigned

Targeted therapies: Lenvatinib SELECTs survival benefit


Until the past 4 years, no treatment option existed for patients with refractory differentiated thyroid cancer, who were treated routinely with supportive care. The first drug to be approved for these patients by the FDA was sorafenib in 2013, followed by lenvatinib in 2015 —

Breast cancer: Microenvironment mediates differential resistance


Despite being effective, and approved for the treatment of a wide range of tumours, targeted therapies are generally less effective against brain metastases. Now, research using mouse models of brain metastases confirms that the PI3K inhibitor buparlisib is effective against tumours located in mammary fat

Immunotherapy: Neuropilin-1 is required for Treg stability


The development of an anticancer immune response is often precluded by an immunosuppressive microenvironment, which can be created by the presence of large numbers of regulatory T cells (Treg). The findings of research using a mouse model of melanoma demonstrate the importance of

Haematological cancer: Genomic disruption of CD7 avoids fractricide


The risk of T-cell fractricide, a situation in which chimeric antigen receptor (CAR) T cells are toxic to each other, owing to the expression of multiple shared antigens by malignant and nonmalignant cells, precludes the use of CAR T-cell-based therapies in patients with T-cell malignancies.

Immunotherapy: PD-1 blockade exploiting MMR deficiency


Mismatch-repair deficiency (dMMR) is a feature of a considerable proportion of tumours, across a range of cancer types. These tumours typically harbour thousands of mutations and are postulated to present neoantigens that might be exploited for effective immunotherapy. New data reported by Dung Le

Haematological cancer: Feasible mutation-targeted therapy


Approximately one-third of patients with acute myeloid leukaemia (AML) harbour mutations in FLT3, which encodes receptor-type tyrosine-protein kinase FLT3. Now, the therapeutic potential of the multikinase inhibitor midostaurin has been explored in this patient population in a study led by Richard Stone, with promising

Breast cancer: Olaparib improves PFS


A synthetic lethal interaction exists between mutations affecting BRCA1 or BRCA2 and the inhibition of some enzymes from the poly [ADP-ribose] polymerase (PARP) family. Notably, 5% of patients with breast cancer harbour germ-line mutations in BRCA1/2. The recently published results of a

Haematological cancer: Brentuximab vedotin — a new standard for cutaneous T-cell lymphoma


Cutaneous T-cell lymphomas, including mycosis fungoides (MF) and primary cutaneous anaplastic large-cell lymphoma (pcALCL), are generally incurable, and have considerable detrimental effects on quality of life and, often, survival. Treatment options are limited, particularly for advanced-stage disease, and no preferred systemic therapy has been established.

Haematological cancer: Where are we now with the treatment of multiple myeloma?


The current standard-of-care therapy for patients with multiple myeloma is autologous stem-cell transplantation; however, whether this approach should be enhanced or displaced by triplet combination therapy is the subject of ongoing debate. We discuss the latest trial that has attempted to address this question and the impact of transplantation and triplet therapy assessment and surrogate end points in future trial design.

Targeted agents and immunotherapies: optimizing outcomes in melanoma


Treatment options for patients with metastatic melanoma, and especially BRAF-mutant melanoma, have changed dramatically in the past 5 years, with the FDA approval of eight new therapeutic agents. During this period, the treatment paradigm for BRAF-mutant disease has evolved rapidly: the standard-of-care BRAF-targeted

Charged-particle therapy in cancer: clinical uses and future perspectives


Radiotherapy with high-energy charged particles has become an attractive therapeutic option for patients with several tumour types because this approach better spares healthy tissue from radiation than conventional photon therapy. The cost associated with the delivery of charged particles, however, is higher than that of

Scientific advice — is drug repurposing missing a trick?


Scientific Advice meetings are a mechanism to improve communications between drug developers and regulators during the drug-development process. While standard practice for industry, the benefits provided by these meetings are under-utilised by academia. In the context of drug repurposing, can scientific advice, as part of a proposed new R&D tax credits scheme, help to unblock some of the obstacles in the way to clinical adoption?

Early phase clinical trials of anticancer agents in children and adolescents — an ITCC perspective


In the past decade, the landscape of drug development in oncology has evolved dramatically; however, this paradigm shift remains to be adopted in early phase clinical trial designs for studies of molecularly targeted agents and immunotherapeutic agents in paediatric malignancies. In drug development, prioritization of

The need for multidisciplinarity in specialist training to optimize future patient care


Harmonious interactions between radiation, medical, interventional and surgical oncologists, as well as other members of multidisciplinary teams, are essential for the optimization of patient care in oncology. This multidisciplinary approach is particularly important in the current landscape, in which standard-of-care approaches to cancer treatment are