![]() This article is highlighted in the In This Issue feature, p. Patient-derived in vitro and in vivo model systems are used to confirm the LAMTOR1-AKT1 fusion as a tumorigenic driver and identify potential mechanisms of resistance to AKT inhibition. SIGNIFICANCE: This study describes the patient-driven discovery of the first AKT1 fusion-driven cancer and its treatment with the AKT inhibitor ipatasertib. Post-clinical validation using patient-derived model systems corroborated these findings, confirmed a membrane-bound and constitutively active fusion protein, and identified potential mechanisms of resistance to single-agent treatment with ipatasertib. Treatment resulted in dramatic tumor regression, demonstrating through patient-driven discovery that the fusion resulted in activation of AKT1, was an oncogenic driver, and could be therapeutically targeted with clinical benefit. Through expanded use access, she became the first pediatric patient to be treated with the oral ATP-competitive pan-AKT inhibitor ipatasertib. A 12-year-old female with a histopathologically indeterminate epithelioid neoplasm was found to harbor a novel fusion between the LAMTOR1 and AKT1 genes. The judgment of the district court is thus AFFIRMED.Despite the important role of the PI3K/AKT/mTOR axis in the pathogenesis of cancer, to date there have been few functional oncogenic fusions identified involving the AKT genes. Sanchez properly concedes that his argument is foreclosed in light of Almendarez-Torres and circuit precedent, but he raises it here to preserve it for further review. ![]() ![]() 466 (2000), we have repeatedly rejected such arguments on the basis that Almendarez-Torres remains binding. Although Sanchez contends that Almendarez-Torres was incorrectly decided and that a majority of the Supreme Court would overrule Almendarez-Torres in light of Apprendi v. ยง 1326 is foreclosed by Almendarez-Torres v. Sanchez s constitutional challenge to 8 U.S.C. Therefore, he cannot demonstrate plain error. Sanchez has failed to establish that the error affected his substantial rights. ![]() We review Sanchez s Booker-based challenge for plain error. 04-41761 -2the waiver provision in this case because the issues that Sanchez raises lack arguable merit or are foreclosed. 47.5, the court has determined that this opinion should not be published and is not precedent except under the limited circumstances set forth in 5TH CIR. * We need not decide the applicability of Pursuant to 5TH CIR. Sanchez also asserts that the felony and aggravated felony provisions of 8 U.S.C. For the first time on appeal, Sanchez asserts that the district court s belief during sentencing that the Federal Sentencing Guidelines were mandatory, rather than advisory, is reversible error under United States v. PER CURIAM:* Jose Filemon Sanchez-Valdivia (Sanchez) appeals his sentence for illegal reentry after being deported subsequent to an aggravated felony conviction. 1:04-CR-705-ALL -Before GARZA, DENNIS, and PRADO, Circuit Judges. Appeal from the United States District Court for the Southern District of Texas USDC No. 04-41761 Conference Calendar UNITED STATES OF AMERICA, Plaintiff-Appellee, versus JOSE FILEMON SANCHEZ-VALDIVIA, Defendant-Appellant. United States Court of Appeals Fifth Circuit F I L E D IN THE UNITED STATES COURT OF APPEALS FOR THE FIFTH CIRCUIT FebruCharles R.
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