Immunotherapy in colorectal cancer: rationale, challenges and potential

Nature Reviews Gastroenterology & Hepatology, Год журнала: 2019, Номер 16(6), С. 361 - 375

Опубликована: Март 18, 2019

Язык: Английский

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Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Journal of the National Comprehensive Cancer Network, Год журнала: 2021, Номер 19(3), С. 329 - 359

Опубликована: Март 1, 2021

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section. These include recommendations first-line use checkpoint inhibitors mCRC, that is deficient mismatch repair/microsatellite instability-high, related biosimilars, and expanded biomarker testing. The now targeted patients with mCRC HER2-amplified, or BRAF V600E mutation–positive. Treatment management nonmetastatic resectable/ablatable disease are discussed complete version available at NCCN.org . Additional topics covered risk assessment, staging, pathology, posttreatment surveillance, survivorship.

Язык: Английский

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Encorafenib, Binimetinib, and Cetuximab in BRAF V600E–Mutated Colorectal Cancer

New England Journal of Medicine, Год журнала: 2019, Номер 381(17), С. 1632 - 1643

Опубликована: Сен. 30, 2019

Patients with metastatic colorectal cancer the BRAF V600E mutation have a poor prognosis, median overall survival of 4 to 6 months after failure initial therapy. Inhibition alone has limited activity because pathway reactivation through epidermal growth factor receptor signaling.

Язык: Английский

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Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients

Science Translational Medicine, Год журнала: 2019, Номер 11(513)

Опубликована: Окт. 9, 2019

There is a clear and unmet clinical need for biomarkers to predict responsiveness chemotherapy cancer. We developed an in vitro test based on patient-derived tumor organoids (PDOs) from metastatic lesions identify nonresponders standard-of-care colorectal cancer (CRC). In prospective study, we show the feasibility of generating testing PDOs evaluation sensitivity chemotherapy. Our PDO predicted response biopsied lesion more than 80% patients treated with irinotecan-based therapies without misclassifying who would have benefited treatment. This correlation was specific chemotherapy, however, failed outcome treatment 5-fluorouracil plus oxaliplatin. data suggest that could be used prevent undergoing ineffective

Язык: Английский

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Genetic diversity of tumors with mismatch repair deficiency influences anti–PD-1 immunotherapy response

Science, Год журнала: 2019, Номер 364(6439), С. 485 - 491

Опубликована: Май 2, 2019

Tumors with mismatch repair deficiency (MMR-d) are characterized by sequence alterations in microsatellites and can accumulate thousands of mutations. This high mutational burden renders tumors immunogenic sensitive to programmed cell death-1 (PD-1) immune checkpoint inhibitors. Yet, despite their tumor immunogenicity, patients MMR-deficient experience highly variable responses, roughly half refractory treatment. We present experimental clinical evidence showing that the degree microsatellite instability (MSI) resultant load, part, underlies response PD-1 blockade immunotherapy MMR-d human mouse tumors. The extent is particularly associated accumulation insertion-deletion (indel) load. study provides a rationale for genome-wide characterization MSI intensity load better profile responses anti-PD-1 across cancers.

Язык: Английский

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Genomic characterization of metastatic patterns from prospective clinical sequencing of 25,000 patients

Cell, Год журнала: 2022, Номер 185(3), С. 563 - 575.e11

Опубликована: Фев. 1, 2022

Язык: Английский

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Quantitative evidence for early metastatic seeding in colorectal cancer

Nature Genetics, Год журнала: 2019, Номер 51(7), С. 1113 - 1122

Опубликована: Июнь 17, 2019

Язык: Английский

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Spatiotemporal Immune Landscape of Colorectal Cancer Liver Metastasis at Single-Cell Level

Cancer Discovery, Год журнала: 2021, Номер 12(1), С. 134 - 153

Опубликована: Авг. 20, 2021

Abstract Liver metastasis, the leading cause of colorectal cancer mortality, exhibits a highly heterogeneous and suppressive immune microenvironment. Here, we sequenced 97 matched samples by using single-cell RNA sequencing spatial transcriptomics. Strikingly, metastatic microenvironment underwent remarkable reprogramming immunosuppressive cells such as MRC1+ CCL18+ M2-like macrophages. We further developed scMetabolism, computational pipeline for quantifying metabolism, observed that those macrophages harbored enhanced metabolic activity. Interestingly, neoadjuvant chemotherapy could block this status restore antitumor balance in responsive patients, whereas nonresponsive patients deteriorated into more one. Our work described evolution metastasis uncovered black box how tumors respond to chemotherapy. Significance: present atlas liver found metabolically activated sites. Efficient can slow down activation, raising possibility target metabolism pathways metastasis. This article is highlighted In Issue feature, p. 1

Язык: Английский

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Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E–Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study

Journal of Clinical Oncology, Год журнала: 2021, Номер 39(4), С. 273 - 284

Опубликована: Янв. 27, 2021

BEACON CRC evaluated encorafenib plus cetuximab with or without binimetinib versus investigators' choice of irinotecan FOLFIRI in patients BRAFV600E-mutant metastatic colorectal cancer (mCRC), after progression on 1-2 prior regimens. In the previously reported primary analysis, encorafenib, (ENCO/BINI/CETUX; triplet) and (ENCO/CETUX; doublet) regimens improved overall survival (OS) objective response rate (ORR; by blinded central review) standard care. The purpose this analysis was to report updated efficacy safety data.In open-label, phase III trial, 665 BRAF V600E-mutant mCRC were randomly assigned 1:1:1 receive triplet, doublet, control. Primary end points OS independently reviewed ORR comparing triplet for doublet control a key secondary point. Updated analyses include 6 months additional follow-up all randomized patients.Patients received (n = 224), 220), 221). Median 9.3 (95% CI, 8.2 10.8) 5.9 5.1 7.1) (hazard ratio [HR], 0.60 [95% 0.47 0.75]). 8.0 11.3) (HR v control, 0.61 0.48 0.77]). Confirmed 26.8% 21.1% 33.1%) 19.5% 14.5% 25.4%) 1.8% 0.5% 4.6%) Adverse events consistent grade ≥ 3 adverse 65.8%, 57.4%, 64.2% respectively.In study, OS, ORR, progression-free treated setting compared chemotherapy. Based analyses, is new care regimen V600E mCRC.

Язык: Английский

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Clinical management of metastatic colorectal cancer in the era of precision medicine

CA A Cancer Journal for Clinicians, Год журнала: 2022, Номер 72(4), С. 372 - 401

Опубликована: Апрель 26, 2022

Colorectal cancer (CRC) represents approximately 10% of all cancers and is the second most common cause deaths. Initial clinical presentation as metastatic CRC (mCRC) occurs in 20% patients. Moreover, up to 50% patients with localized disease eventually develop metastases. Appropriate management these still a challenging medical issue. Major efforts have been made unveil molecular landscape mCRC. This has resulted identification several druggable tumor targets aim developing personalized treatments for each patient. review summarizes improvements mCRC emerging era precision medicine. In fact, stratification, on which current treatment algorithm based, although it does not completely represent complexity this disease, first significant step toward clinically informative genetic profiling implementing more effective therapeutic approaches. relevant increase control patient survival. The next steps will be integrate comprehensive knowledge gene alterations, microenvironment protein expression profiling, host immune competence well application resulting dynamic changes medicine-based continuum care approach could result individual prognostic predictive parameters, help clinician choosing appropriate program(s) throughout entire journey CA Cancer J Clin. 2022;72:000-000.

Язык: Английский

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