Role of Deficient Mismatch Repair in the Personalized Management of Colorectal Cancer

Zhang, Congmin; Lv, Jidong; Gong, Liang; Yu, Linyu; Chen, Xiaoping; Zhou, Hong‐Hao; Li, Fan

doi:10.3390/ijerph13090892

Cited by 49 publications

(49 citation statements)

References 114 publications

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“…Our observation that dMMR tumours were associated with reduced levels of VEGF-1 compared to pMMR tumours, was in line with previous studies (14)(15)(16)(17). Most of these studies, however, did not identify the relationship between MMR genes (i.e., MSH2, MLH1, MSH6, and PMS2) and VEGF-1 expression in dMMR mCRCs.…”

Section: Discussionsupporting

confidence: 91%

Patients with hMLH1 or/and hMSH2-deficient Metastatic Colorectal Cancer Are Associated with Reduced Levels of Vascular Endothelial Growth Factor-1 Expression and Higher Response Rate to Irinotecan-based Regimen

Bendardaf

Sharif-Askari

et al. 2018

Anticancer Res

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Background/Aim: The benefit of IFL (irinotecan, fluorouracil and leucovorin) regimen for metastatic colorectal cancer patients (mCRCs) with high levels of microsatellite instability (MSI-H) or loss of mismatch repair (dMMR) protein expression, is uncertain. This study investigated the association of tumour MMR-status and VEGF-1 expression with response to first-line IFL regimen in mCRCs. Patients and Methods: This prospective study analyzed patients diagnosed with mCRC between August 1st, 1998, and August 30th, 2003, at the Turku University Hospital, Finland. All patients received postoperative IFL regimen. Tumour expression of the MMR proteins, hMLH1 and hMSH2, and VEGF-1 expression were assessed by immunohistochemistry (IHC). Tumours with dMMR were those demonstrating loss of MMR protein expression, and tumours with high VEGF-1 expression were those showing moderate or strong cytoplasmic staining. The primary endpoint was the association between tumour hMLH1 or/and hMSH2-deficient and VEGF-1 expression; the relation between tumour MMRstatus and IFL response rate was the secondary endpoint. Results: Of the 67 mCRCs patients, 29 (43%) were hMLH1 or/and hMSH2-deficient and 15 (22%) were pMMR mCRCs.At diagnosis, patients with hMLH1 or/and hMSH2-deficient tumours expressed lower levels of VEGF-1 compared to pMMR tumour patients (p=0.01). More than half (n=17, 59%) of those with dMMR were chemosensitive to first-line IFL regimen, while just one-fifth (n=3, 20%) of those with pMMR were chemosensitive to the IFL regimen (p=0.045). Conclusion: Association between MMR-status and VEGF-1 expression predicts clinical outcome in mCRC patients. 6399

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Section: Discussionsupporting

confidence: 91%

Patients with hMLH1 or/and hMSH2-deficient Metastatic Colorectal Cancer Are Associated with Reduced Levels of Vascular Endothelial Growth Factor-1 Expression and Higher Response Rate to Irinotecan-based Regimen

Bendardaf

Sharif-Askari

et al. 2018

Anticancer Res

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“…Although the immunotherapy approaches still suffer from drawbacks including induced therapeutic resistance and immune‐related unfavorable outcomes, it is considered as one of the most successful strategies against CRC. Immunotherapy with anti‐PD‐1 agents has a possible advantage for immunogenic MSI‐H CRCs without any robust evidence to suggest the effectiveness of immunotherapy in MSS CRCs (Toh et al, 2016; C. M. Zhang et al, 2016). Different genetic alterations provide the opportunity for tumor cells to escape immune surveillance.…”

Section: Immune Responses and Immune Resistance In Crcmentioning

confidence: 99%

“…Immunotherapy with anti-PD-1 agents has a possible advantage for immunogenic MSI-H CRCs without any robust evidence to suggest the effectiveness of immunotherapy in MSS CRCs (Toh et al, 2016; C. M. Zhang et al, 2016). Different genetic alterations provide the opportunity for tumor cells to escape immune surveillance.…”

Section: Features Of Cms1mentioning

confidence: 99%

PD‐1/PD‐L1‐dependent immune response in colorectal cancer

Payandeh

Khalili

Somi

et al. 2020

Journal Cellular Physiology

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Colorectal cancer (CRC) is still considered as the third most frequent cancer in the world. Microsatellite instability (MSI), inflammation, and microRNAs have been demonstrated as the main contributing factors in CRC. Subtype 1 CRC is defined by NK cells infiltration, induction of Th1 lymphocyte and cytotoxic T cell responses as well as upregulation of immune checkpoint proteins including programmed cell death‐1 (PD‐1). Based on the diverse features of CRC, such as the stage and localization of the tumor, several treatment approaches are available. However, the efficiency of these treatments may be decreased due to the development of diverse resistance mechanisms. It has been proven that monoclonal antibodies (mAbs) can increase the effectiveness of CRC treatments. Nowadays, several mAbs including nivolumab and pembrolizumab have been approved for the treatment of CRC. Immune checkpoint receptors including PD‐1 can be inhibited by these antibodies. Combination therapy gives an opportunity for advanced treatment for CRC patients. In this review, an update has been provided on the molecular mechanisms involved in MSI colorectal cancer immune microenvironment by focusing on PD‐ligand 1 (PD‐L1) and treatment of patients with advanced immunotherapy, which were examined in the different clinical trial phases. Considering induced expression of PD‐L1 by conventional chemotherapeutics, we have summarized the role of PD‐L1 in CRC, the chemotherapy effects on the PD‐1/PD‐L1 axis and novel combined approaches to enhance immunotherapy of CRC by focusing on PD‐L1.

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“…El cáncer colorrectal en estadio clínico III con deficiencia de la reparación del mal apareamiento del ADN (dMMR), ubicado en el colon distal o con un estado ganglionar N2, tiene un pronóstico malo; esto, independientemente del resultado adverso por mutaciones de KRAS o BRAF 93,94 .…”

Section: Utilidad De La Valoración Del Estado De Los Genes En La Prácunclassified

¿Existen ventajas clínicas al evaluar el estado de los genes KRAS, NRAS, BRAF, PIK3CA, PTEN y HER2 en pacientes con cáncer colorrectal?

2017

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Role of Deficient Mismatch Repair in the Personalized Management of Colorectal Cancer

Cited by 49 publications

References 114 publications

Patients with hMLH1 or/and hMSH2-deficient Metastatic Colorectal Cancer Are Associated with Reduced Levels of Vascular Endothelial Growth Factor-1 Expression and Higher Response Rate to Irinotecan-based Regimen

Patients with hMLH1 or/and hMSH2-deficient Metastatic Colorectal Cancer Are Associated with Reduced Levels of Vascular Endothelial Growth Factor-1 Expression and Higher Response Rate to Irinotecan-based Regimen

PD‐1/PD‐L1‐dependent immune response in colorectal cancer

¿Existen ventajas clínicas al evaluar el estado de los genes KRAS, NRAS, BRAF, PIK3CA, PTEN y HER2 en pacientes con cáncer colorrectal?

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