Медицинская библиотека · ESMO open · 2025

Genomic profiling of high tumor mutational load in microsatellite-stable colorectal cancer uncovers MAPK signaling pathway alterations following anti-EGFR therapy.

Boscolo Bielo L, Napolitano S, Avallone A, Pietrantonio F, Bordonaro R, Maiello E, Pisconti S, Tamburini E, Lotesoriere C, Tortora G, Zaniboni A, Blasi L, Antonuzzo L, Berardi R, Tagliaferri P, Cremolini C, Lonardi S, Garufi C, Pinto C, Ongaro E, Santabarbara G, Scartozzi M, De Falco V, De Stefano A, Cardone C, Iacovucci A, Bosco M F, Russo A E, Latiano T P, Nisi C, Messina M, Salmistraro N, Sartore-Bianchi A, Siena S, Zampino M G, Fazio N, Normanno N, Febbraro A, Guerrera L P, Parente P, De Vita F, Martinelli E, Troiani T, Curigliano G, Ciardiello F, Martini G, Ciardiello D

СтатьяПеревод в очереди

Аннотация

BACKGROUND

Translational studies have provided evidence that targeted therapies and chemotherapy might induce a status of adaptive mutability with an increase in the tumor mutational load.

PATIENTS AND

METHODS

We conducted an analysis of pathogenic variants (PVs) detected by liquid biopsy (LBx)-based comprehensive genomic profiling in patients with chemo-refractory microsatellite-stable metastatic colorectal cancer (mCRC) pretreated with anti-epidermal growth factor receptor (EGFR) within the VELO and CAVE-2 GOIM studies compared with anti-EGFR naïve mCRC included in the CAPRI-2 GOIM trial.

RESULTS

Overall, 559 patients with available samples for LBx analysis were included. EGFR pretreated tumors had significant enrichment for PVs in the MAPK signaling pathway with a median tumor mutational burden (TMB) [6 interquartile range (IQR 4-11) versus 4 (IQR 3-9), P < 0.0001]; 33.8% pretreated patients had TMB with ≥10 mutations per megabase compared with 9.7% patients before first-line anti-EGFR treatment. Higher mutational load correlated with KRAS (q = 0.07), BRAFV600 (q = 0.01), ERBB2 AMP (q = 0.06) and EGFR ECD (q = 0.07) PVs. Such association was not observed in patients naïve to anti-EGFR drugs. MAPK mutations were associated with higher TMB in anti-EGFR pretreated samples (beta = 4.0, P < 0.0001), but not in anti-EGFR-naïve samples (beta 1.2, P = 0.4).

CONCLUSION

These findings might support the investigation of immunotherapy in patients with mCRC pretreated with EGFR inhibitors with high mutational load.

Для цитирования: Boscolo Bielo L, Napolitano S, Avallone A, Pietrantonio F, Bordonaro R, Maiello E, Pisconti S, Tamburini E, Lotesoriere C, Tortora G, Zaniboni A, Blasi L, Antonuzzo L, Berardi R, Tagliaferri P, Cremolini C, Lonardi S, Garufi C, Pinto C, Ongaro E, Santabarbara G, Scartozzi M, De Falco V, De Stefano A, Cardone C, Iacovucci A, Bosco M F, Russo A E, Latiano T P, Nisi C, Messina M, Salmistraro N, Sartore-Bianchi A, Siena S, Zampino M G, Fazio N, Normanno N, Febbraro A, Guerrera L P, Parente P, De Vita F, Martinelli E, Troiani T, Curigliano G, Ciardiello F, Martini G, Ciardiello D. Genomic profiling of high tumor mutational load in microsatellite-stable colorectal cancer uncovers MAPK signaling pathway alterations following anti-EGFR therapy.. ESMO open. 2025. DOI: 10.1016/j.esmoop.2025.105877.

Предметные рубрики MeSH

Humans Colorectal Neoplasms ErbB Receptors Female Male Middle Aged Aged Mutation MAP Kinase Signaling System Microsatellite Instability Antineoplastic Agents

Подготовка и перевод публикации

Обработка статьи · этапы, ошибки и управление

Загрузка состояния…

История · было → стало

Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.