New England Journal of Medicine

Ferdinandos Skoulidis, M.D., Ph.D., Bob T. Li, M.D., Ph.D., M.P.H., Grace K. Dy, M.D., Timothy J. Price, M.B., B.S., D.H.Sc., Gerald S. Falchook, M.D., Jürgen Wolf, M.D., Antoine Italiano, M.D., Martin Schuler, M.D., Hossein Borghaei, D.O., Fabrice Barlesi, M.D., Ph.D., Terufumi Kato, M.D., Alessandra Curioni-Fontecedro, M.D., et al.

doi : 10.1056/NEJMoa2103695

N Engl J Med 2021; 384:2371-2381

Sotorasib showed anticancer activity in patients with KRAS p.G12C–mutated advanced solid tumors in a phase 1 study, and particularly promising anticancer activity was observed in a subgroup of patients with non–small-cell lung cancer (NSCLC).

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Acquired Resistance to KRASG12C Inhibition in Cancer

Mark M. Awad, M.D., Ph.D., Shengwu Liu, Ph.D., Igor I. Rybkin, M.D., Ph.D., Kathryn C. Arbour, M.D., Julien Dilly, M.S., Viola W. Zhu, M.D., Ph.D., Melissa L. Johnson, M.D., Rebecca S. Heist, M.D., M.P.H., Tejas Patil, M.D., Gregory J. Riely, M.D., Ph.D., Joseph O. Jacobson, M.D., Xiaoping Yang, Ph.D., et al.

doi : 10.1056/NEJMoa2105281

N Engl J Med 2021; 384:2382-2393

Clinical trials of the KRAS inhibitors adagrasib and sotorasib have shown promising activity in cancers harboring KRAS glycine-to-cysteine amino acid substitutions at codon 12 (KRASG12C). The mechanisms of acquired resistance to these therapies are currently unknown.

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Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer

Andrew N.J. Tutt, M.B., Ch.B., Ph.D., Judy E. Garber, M.D., M.P.H., Bella Kaufman, M.D., Giuseppe Viale, M.D., Debora Fumagalli, M.D., Ph.D., Priya Rastogi, M.D., Richard D. Gelber, Ph.D., Evandro de Azambuja, M.D., Ph.D., Anitra Fielding, M.B., Ch.B., Judith Balma?a, M.D., Ph.D., Susan M. Domchek, M.D., Karen A. Gelmon, M.D., et al., for the OlympiA Clinical Trial Steering Committee and Investigators*

doi : 10.1056/NEJMoa2105215

N Engl J Med 2021; 384:2394-2405

Poly(adenosine diphosphate–ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation–associated early breast cancer.

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Developmental Consequences of Defective ATG7-Mediated Autophagy in Humans

Jack J. Collier, Ph.D., Claire Guissart, Pharm.D., Monika Ol?hov?, Ph.D., Souphatta Sasorith, Ph.D., Florence Piron-Prunier, M.Sc., Fumi Suomi, Ph.D., David Zhang, M.Sc., Nuria Martinez-Lopez, Ph.D., Nicolas Leboucq, M.D., Angela Bahr, Ph.D., Silvia Azzarello-Burri, M.D., Selina Reich, M.Sc., et al.

doi : 10.1056/NEJMoa1915722

N Engl J Med 2021; 384:2406-2417

Autophagy is the major intracellular degradation route in mammalian cells. Systemic ablation of core autophagy-related (ATG) genes in mice leads to embryonic or perinatal lethality, and conditional models show neurodegeneration. Impaired autophagy has been associated with a range of complex human diseases, yet congenital autophagy disorders are rare.

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Azithromycin or Doxycycline for Asymptomatic Rectal Chlamydia trachomatis

Andrew Lau, M.S., Fabian Y.S. Kong, Ph.D., Christopher K. Fairley, Ph.D., David J. Templeton, Ph.D., Janaki Amin, Ph.D., Samuel Phillips, Ph.D., Matthew Law, Ph.D., Marcus Y. Chen, Ph.D., Catriona S. Bradshaw, Ph.D., Basil Donovan, M.D., Anna McNulty, M.D., Mark A. Boyd, M.D., et al.

doi : 10.1056/NEJMoa2031631

N Engl J Med 2021; 384:2418-2427

Rectal chlamydia is a common bacterial sexually transmissible infection among men who have sex with men. Data from randomized, controlled trials are needed to guide treatment.

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