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In this issue, we are launching a Series on Cancer Therapy comprising commissioned Reviews and Perspectives that highlight emerging concepts, recent advances and the challenges ahead in cancer therapy, and a selection of primary research articles on this topic published in Nature Cancer.
Cancer therapies have evolved considerably in recent decades, substantially improving the quality of life and survival of patients with cancer. In this issue, we launch our Series on Cancer Therapy, exploring current paradigms and recent advances and challenges in this field, through specially commissioned articles.
Cancer research has undergone transformational changes over the past several decades. On the occasion of the 20th anniversary of the establishment of the NCI Center for Cancer Research, we highlight some elements that enable successful institutional approaches to solving the most pressing problems in cancer research.
Shedding light on the mechanisms that underlie a durable response to immunotherapy, a recent study evaluating long-term survivors of melanoma treated with immunotherapy finds that tumor-associated T cell clonotypes are sustained over years and persist as expanded, cytokine IFN-γ–expressing resident memory T cells in the skin, with effector memory counterparts in the blood.
Pharmacogenomic drug screening provides a promising platform for the discovery of anti-cancer drugs, in combination with biomarkers and mechanisms that confer therapeutic response. A study now pinpoints the mechanisms of sensitivity to dasatinib in T-ALL leukemia, identifying a T cell–differentiation switch that determines sensitivity to distinct drug modalities.
Kang and colleagues review recent advances and challenges in developing therapies for metastatic cancer and the clinical implications of ongoing and completed studies for metastatic disease.
Mukhopadhyay, Vander Heiden and McCormick review the metabolic landscape of RAS-driven cancers, the effects of RAS-directed metabolic reprogramming and opportunities for targeting these cancers therapeutically.
Yang and colleagues perform a network system–pharmacology approach and clinical data integration, and identify LCK and BCL2 signaling as the molecular determinants of dasatinib response in pediatric and adult patients with T-ALL.
Turk and colleagues analyze exceptional responders to checkpoint blockade for melanoma, and detect tissue-resident memory and effector memory T-cell clonotypes in skin and blood, respectively, up to 9 years after treatment.
Eilers and colleagues report that Aurora-A suppresses transcription–replication conflicts in MYCN-driven neuroblastoma, a vulnerability that can be targeted with a combination of Aurora-A and ATR kinase inhibitors.
Ishikawa and colleagues perform integrated genomic and drug-sensitivity screens with extensive PDX modeling and reveal combined XIAP and BCL2 inhibition as a vulnerability hub across AML genetic alterations.
Walsh and colleagues use prospective sequencing in a large cohort of pediatric patients with solid tumors to detect mutations in cancer predisposition genes and guide downstream clinical care.