NSABP FC-9: Phase II study of dual immune checkpoint blockade (ICB) with durvalumab (D) plus tremelimumab (T) following palliative hypofractionated radiotherapy (SBRT) in patients (pts) with microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) progressing on chemotherapy.

Lee, James J.; Yothers, Greg; George, Thomas J.; Fakih, Marwan; Mallick, Atrayee Basu; Maalouf, Bassam Nabih; Krauss, John C.; Heron, Dwight E.; Allegra, Carmen J.; Jacobs, Samuel A.

doi:10.1200/jco.2018.36.15_suppl.e15681

Cited by 2 publications

(1 citation statement)

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“…Finally, targeting WNT/β-catenin signaling, whose activation is more frequent in pMMR/MSS CRC and is involved in the mechanism of immune exclusion, is under consideration to improve IT efficacy; this is achieved by inducing transcriptional repression of chemokine genes, such as C-C motif chemokine 4, which is important for the intratumoral homing of dendritic cells to the tumor bed. The latest emerging trials that involved combination strategies to overcome resistance are reported in Table III (48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66).…”

Section: Discussionmentioning

confidence: 99%

PD‑1/PD‑L1 blockade, a novel strategy for targeting metastatic colorectal cancer: A systematic review and meta‑analysis of randomized trials

Rotundo¹,

Bagnardi

Comandè³

et al. 2022

Oncol Lett

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Currently, standard treatment of patients with metastatic colorectal cancer (mCRC) comprises chemotherapy (CT) and/or biological therapy (BT) and/or best supportive care (BSC). The present study performed a meta-analysis on five phase II-III randomized clinical trials, which compared CT/BT/BSC as the control arm with the immune checkpoint inhibitors (ICIs) anti-programmed cell death protein 1 (PD-1) or its ligand (PD-L1) alone or in combination with cytotoxic T lymphocyte antigen 4 or mitogen activated protein kinase kinase inhibitors as the experimental arm, to evaluate whether a standard approach could be overcome using the novel target therapy strategy. Pooled hazard ratio (HR) for progression-free survival was 0.95 in favor of the experimental arm [95% confidence interval (CI), 0.74-1.22; P= 0.68]. Heterogeneity was significant: Cochran's Q, 21.0; P= 0.0082; I 2 index, 76%. Pooled HR for overall survival was 0.88 in favor of the experimental arm (95% CI, 0.75-1.02; P=0.08). Heterogeneity was not significant (Cochran's Q, 6.0; P=0.31; I 2 index, 16%). The present meta-analysis demonstrated a trend toward the improvement of survival by PD-1/PD-L1 blockade in mCRC. Further homogeneous studies are necessary to strengthen these results, beyond the known benefits of ICIs in deficient mismatch repair/high microsatellite instability tumors.

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Section: Discussionmentioning

confidence: 99%

PD‑1/PD‑L1 blockade, a novel strategy for targeting metastatic colorectal cancer: A systematic review and meta‑analysis of randomized trials

Rotundo¹,

Bagnardi

Comandè³

et al. 2022

Oncol Lett

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From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies

Gharib,

Robichaud

2024

IJMS

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Colorectal cancer (CRC) represents a significant global health burden, with high incidence and mortality rates worldwide. Recent progress in research highlights the distinct clinical and molecular characteristics of colon versus rectal cancers, underscoring tumor location’s importance in treatment approaches. This article provides a comprehensive review of our current understanding of CRC epidemiology, risk factors, molecular pathogenesis, and management strategies. We also present the intricate cellular architecture of colonic crypts and their roles in intestinal homeostasis. Colorectal carcinogenesis multistep processes are also described, covering the conventional adenoma–carcinoma sequence, alternative serrated pathways, and the influential Vogelstein model, which proposes sequential APC, KRAS, and TP53 alterations as drivers. The consensus molecular CRC subtypes (CMS1-CMS4) are examined, shedding light on disease heterogeneity and personalized therapy implications.

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NSABP FC-9: Phase II study of dual immune checkpoint blockade (ICB) with durvalumab (D) plus tremelimumab (T) following palliative hypofractionated radiotherapy (SBRT) in patients (pts) with microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) progressing on chemotherapy.

Cited by 2 publications

References 0 publications

PD‑1/PD‑L1 blockade, a novel strategy for targeting metastatic colorectal cancer: A systematic review and meta‑analysis of randomized trials

PD‑1/PD‑L1 blockade, a novel strategy for targeting metastatic colorectal cancer: A systematic review and meta‑analysis of randomized trials

From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies

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