Immunotherapy in colorectal cancer: is the long-awaited revolution finally happening?

Arrichiello, Gianluca; Poliero, L.; Borrelli, C.; Paragliola, Fernando; Nacca, Valeria; Napolitano, Stefania; Corte, Carminia Maria Della; Martini, Giulia; Martinelli, Erika

doi:10.1016/j.ctarc.2021.100442

Cited by 16 publications

(15 citation statements)

References 89 publications

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“…Although these tumors are a small subgroup of mCRC (approximately 5% of cases), the introduction of immune checkpoint inhibitors has been a revolution in the precision medicine approach to mCRC therapies. 163 Two anti-PD-1 monoclonal antibodies-pembrolizumab and nivolumab-and the combination of nivolumab plus the anti-CTLA-4 monoclonal antibody ipilimumab have been approved by the FDA for the treatment of patients with MSI-H/dMMR mCRC. 164 According to phase 2 data, 165 the combination of nivolumab plus ipilimumab seems to be more effective in terms of increased objective responses, disease control, and survival compared with nivolumab monotherapy (Table 8).…”

Section: Integrating Immunotherapies In the Continuum Of Care Of Meta...mentioning

confidence: 99%

“…MSI‐H/dMMR is the first predictive biomarker of immunotherapy efficacy for mCRC. Although these tumors are a small subgroup of mCRC (approximately 5% of cases), the introduction of immune checkpoint inhibitors has been a revolution in the precision medicine approach to mCRC therapies 163 . Two anti–PD‐1 monoclonal antibodies—pembrolizumab and nivolumab—and the combination of nivolumab plus the anti–CTLA‐4 monoclonal antibody ipilimumab have been approved by the FDA for the treatment of patients with MSI‐H/dMMR mCRC 164 .…”

Section: Integrating Immunotherapies In the Continuum Of Care Of Meta...mentioning

confidence: 99%

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

Ciardiello

Martini

et al. 2022

CA A Cancer J Clinicians

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253

161

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

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Section: Integrating Immunotherapies In the Continuum Of Care Of Meta...mentioning

confidence: 99%

Section: Integrating Immunotherapies In the Continuum Of Care Of Meta...mentioning

confidence: 99%

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

Ciardiello

Martini

et al. 2022

CA A Cancer J Clinicians

Self Cite

253

161

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“…Mismatch repair deficit is responsible for a fraction of rectal cancers. A recent study was conducted based on the prediction that checkpoint blockade could be helpful in individuals with mismatch repair-deficient, locally progressed rectal cancer because mismatch repair-deficient colorectal cancer responds to PD-1 blockade in the context of metastatic disease [ 33 ]. The neoadjuvant therapy, Fluoropyrimidine, in conjunction with Oxaliplatin is followed by chemoradiotherapy and finally surgery.…”

Section: Rectal Cancermentioning

confidence: 99%

Dostarlimab: A Review

Costa

Vale

2022

Biomolecules

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Dostarlimab (JEMPERLI) is a PD-1 monoclonal antibody for the treatment of adult patients, with mismatch repair deficient (dMMR), recurrent or advanced endometrial cancer that has progressed on or following prior therapy with a platinum-containing regimen. As determined by an FDA-approved test this indication was granted rapid approval based on the rate of tumor response and the duration of the response. Continued approval for this indication is conditioned on further confirmatory trials demonstrating and documenting clinical benefit. In June 2022, the clinical trial NCT04165772 reported a 100% remission rate for rectal cancer. This clinical trial brought proof that we can match a tumor and the genetics of what is driving it, with therapy. This clinical trial continues to enroll patient and is currently enrolling patients with gastric, prostate, and pancreatic cancers. Dostarlamib is being recommended for rectal cancer. The focus of this review is to summarize the existing knowledge regarding Dostarlimab and explore the possibilities of mono- and combination therapies.

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“…Its effect on immune response is mainly to enhance tumor immunogenicity by increasing tumor-recognizable neoantigens, expression of MHC molecules, etc. ( 113 ) And to recruit CD8+ T cells and DC cells to awaken the body’ s anti-tumor immune process ( 114 ). Radiotherapy triggers immunogenic cell death by both of these means ( 115 ), enhances DC function and further promotes antigenic expression of dendritic cells (DCs) ( 116 ), allows DCs to be recruited between tumor tissues.…”

Section: Combined Dna Damage Repair-based Therapy With Immunotherapymentioning

confidence: 99%

DNA Damage Repair in Brain Tumor Immunotherapy

Zhao

et al. 2022

Front. Immunol.

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With the gradual understanding of tumor development, many tumor therapies have been invented and applied in clinical work, and immunotherapy has been widely concerned as an emerging hot topic in the last decade. It is worth noting that immunotherapy is nowadays applied under too harsh conditions, and many tumors are defined as “cold tumors” that are not sensitive to immunotherapy, and brain tumors are typical of them. However, there is much evidence that suggests a link between DNA damage repair mechanisms and immunotherapy. This may be a breakthrough for the application of immunotherapy in brain tumors. Therefore, in this review, first, we will describe the common pathways of DNA damage repair. Second, we will focus on immunotherapy and analyze the mechanisms of DNA damage repair involved in the immune process. Third, we will review biomarkers that have been or may be used to evaluate immunotherapy for brain tumors, such as TAMs, RPA, and other molecules that may provide a precursor assessment for the rational implementation of immunotherapy for brain tumors. Finally, we will discuss the rational combination of immunotherapy with other therapeutic approaches that have an impact on the DNA damage repair process in order to open new pathways for the application of immunotherapy in brain tumors, to maximize the effect of immunotherapy on DNA damage repair mechanisms, and to provide ideas and guidance for immunotherapy in brain tumors.

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Immunotherapy in colorectal cancer: is the long-awaited revolution finally happening?

Cited by 16 publications

References 89 publications

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

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

Dostarlimab: A Review

DNA Damage Repair in Brain Tumor Immunotherapy

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