PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Aug. 18, 2023

Abstract The PI3K/AKT/mTOR (PAM) signaling pathway is a highly conserved signal transduction network in eukaryotic cells that promotes cell survival, growth, and cycle progression. Growth factor signalling to transcription factors the PAM axis regulated by multiple cross-interactions with several other pathways, dysregulation of can predispose cancer development. most frequently activated human often implicated resistance anticancer therapies. Dysfunction components this such as hyperactivity PI3K, loss function PTEN, gain-of-function AKT, are notorious drivers treatment disease progression cancer. In review we highlight major dysregulations cancer, discuss results AKT mTOR inhibitors monotherapy co-administation antineoplastic agents clinical trials strategy for overcoming resistance. Finally, mechanisms targeted therapies, including immunology immunotherapies also discussed.

Language: Английский

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Cancer biomarkers: Emerging trends and clinical implications for personalized treatment

Cell, Journal Year: 2024, Volume and Issue: 187(7), P. 1617 - 1635

Published: March 1, 2024

Language: Английский

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The CDK4/6 inhibitor revolution — a game-changing era for breast cancer treatment

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 21(2), P. 89 - 105

Published: Dec. 11, 2023

Language: Английский

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Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group

Annals of Oncology, Journal Year: 2024, Volume and Issue: 35(7), P. 588 - 606

Published: May 27, 2024

Advancements in the field of precision medicine have prompted European Society for Medical Oncology (ESMO) Precision Medicine Working Group to update recommendations use tumour next-generation sequencing (NGS) patients with advanced cancers routine practice.

Language: Английский

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Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2− advanced breast cancer: final overall survival results of MONARCH 3

Annals of Oncology, Journal Year: 2024, Volume and Issue: 35(8), P. 718 - 727

Published: May 8, 2024

Highlights•This phase III trial evaluated abemaciclib + NSAI versus placebo as initial therapy for HR+, HER2− ABC.•Addition of to an resulted in numerically longer OS; however, statistical significance was not reached.•Absolute improvement median OS clinically meaningful (ITT: 13.1 months; sVD: 14.9 months).•The previously demonstrated PFS benefit with the addition sustained (median 14.3 delayed subsequent receipt chemotherapy 16.1 months).AbstractBackgroundIn MONARCH 2, fulvestrant significantly improved both progression-free survival (PFS) and overall (OS) patients hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) disease progression on prior endocrine therapy. In 3, a nonsteroidal aromatase inhibitor (NSAI) ABC PFS. Here, we present prespecified final results 3.Patients methodsMONARCH 3 is randomized, double-blind, study plus (anastrozole or letrozole) postmenopausal women without systemic setting. The primary objective investigator-assessed PFS; gated secondary endpoint, chemotherapy-free exploratory endpoint.ResultsA total 493 were randomized 2 : 1 receive (n = 328) 165). After follow-up 8.1 years, there 198 events (60.4%) arm 116 (70.3%) (hazard ratio, 0.804; 95% confidence interval 0.637-1.015; P 0.0664, non-significant). Median 66.8 53.7 months placebo. subgroup visceral disease, 113 (65.3%) 65 (72.2%) 0.758; 0.558-1.030; 0.0757, 63.7 48.8 sustained, abemaciclib. No new safety signals observed.ConclusionsAbemaciclib combined (intent-to-treat population: disease: months) HR+ ABC; reached.

Language: Английский

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Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 14, 2024

Outcomes in patients with hormone receptor-positive metastatic breast cancer worsen after one or more lines of endocrine-based therapy. Trastuzumab deruxtecan has shown efficacy low expression human epidermal growth factor receptor 2 (HER2) previous chemotherapy.

Language: Английский

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Inavolisib-Based Therapy in PIK3CA -Mutated Advanced Breast Cancer

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: 391(17), P. 1584 - 1596

Published: Oct. 30, 2024

BackgroundInavolisib is a highly potent and selective inhibitor of the alpha isoform p110 catalytic subunit phosphatidylinositol 3-kinase complex (encoded by PIK3CA) that also promotes degradation mutated p110α. Inavolisib plus palbociclib–fulvestrant has shown synergistic activity in preclinical models promising antitumor early-phase trials.MethodsIn phase 3, double-blind, randomized trial, we compared first-line inavolisib (at an oral dose 9 mg once daily) (inavolisib group) with placebo (placebo patients PIK3CA-mutated, hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative locally advanced or metastatic breast cancer who had relapse during within 12 months after completion adjuvant endocrine therapy. The primary end point was progression-free survival as assessed investigator.Download PDF Plain Language Summary.ResultsA total 161 were assigned to group 164 group; median follow-up 21.3 21.5 months, respectively. 15.0 (95% confidence interval [CI], 11.3 20.5) 7.3 CI, 5.6 9.3) (hazard ratio for disease progression death, 0.43; 95% 0.32 0.59; P<0.001). An objective response occurred 58.4% 25.0% those group. incidence grade 3 4 neutropenia 80.2% 78.4% hyperglycemia, 5.6% 0%, respectively; stomatitis mucosal inflammation, 0%; diarrhea, 3.7% 0%. No rash observed. Discontinuation any trial agent because adverse events 6.8% 0.6% group.ConclusionsIn HER2-negative cancer, led significantly longer than palbociclib–fulvestrant, greater toxic effects. percentage discontinued low. (Funded F. Hoffmann–La Roche; INAVO120 ClinicalTrials.gov number, NCT04191499.) Quick Take Addition PI3Kα Inhibition Breast Cancer 2m 23s

Language: Английский

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6th and 7th International consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7)

The Breast, Journal Year: 2024, Volume and Issue: 76, P. 103756 - 103756

Published: May 28, 2024

This manuscript describes the Advanced Breast Cancer (ABC) international consensus guidelines updated at last two ABC conferences (ABC 6 in 2021, virtual, and 7 2023, Lisbon, Portugal), organized by Global Alliance. It provides main recommendations on how to best manage patients with advanced breast cancer (inoperable locally or metastatic), of all subtypes, as well palliative supportive care. These are based available evidence expert opinion when a higher level is lacking. Each guideline accompanied (LoE), grade recommendation (GoR) percentage reached conferences. Updated diagnostic treatment algorithms also provided. The represent management options for living globally, assuming accessibility therapies. Their adaptation (i.e. resource-stratified guidelines) often needed settings where access care limited.

Language: Английский

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Optimal targeting of PI3K-AKT and mTOR in advanced oestrogen receptor-positive breast cancer

The Lancet Oncology, Journal Year: 2024, Volume and Issue: 25(4), P. e139 - e151

Published: March 25, 2024

Language: Английский

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International multidisciplinary consensus on the integration of radiotherapy with new systemic treatments for breast cancer: European Society for Radiotherapy and Oncology (ESTRO)-endorsed recommendations

The Lancet Oncology, Journal Year: 2024, Volume and Issue: 25(2), P. e73 - e83

Published: Jan. 30, 2024

Language: Английский

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