What is the prognostic impact of <i>BRAF</i> mutation in patients undergoing resection of colorectal liver metastases? Results of nationwide intergroup (ACHBT, FRENCH, AGEO) cohort of 249 patients.

Bachet, Jean‐Baptiste; Moreno-Lopez, Nathan; Viganò, Luca; Marchese, Ugo; Gelli, Maximiliano; Raoux, L.; Truant, Stéphanie; Laurent, Césari; Herrero, Astrid; Roy, Bertrand Le; Lardiere, Sophie Deguelte; Passot, Guillaume; Hautefeuille, Vincent; Fouchardière, Christelle De La; Artru, Pascal; Ameto, T.; Brouquet, Antoine; Cunha, A. Sá; Benoist, Stéphane

doi:10.1200/jco.2018.36.15_suppl.3554

Cited by 2 publications

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“…Recent cohorts have given slightly discordant results. In a French cohort, 93 66 patients underwent resection for BRAF -mutant liver metastases of mCRC. A case-matched comparison was made with 183 patients who underwent resection for BRAF -wild-type liver metastases of mCRC during the same period.…”

Section: Treatment Of Braf-mutant Tumorsmentioning

confidence: 99%

Molecular targeted therapy of BRAF-mutant colorectal cancer

et al. 2019

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Over the past two decades, the molecular characterization of metastatic colorectal cancer (mCRC) has been revolutionized by the routine implementation of RAS and BRAF tests. As a result, it is now known that patients with mCRC harboring BRAF mutations experience a poor prognosis. Although it accounts for only 10% of mCRC, this group is heterogeneous; only the BRAF- V600E mutation, also observed in melanoma, is associated with a very poor prognosis. In terms of treatment, these patients do not benefit from therapeutics targeting the epidermal growth factor receptor (EGFR). In first-line chemotherapy, there are two main options; the first one is to use a triple chemotherapy combination of 5-fluorouracil, irinotecan, and oxaliplatin, with the addition of bevacizumab, because post hoc analysis of randomized trials have reported interesting results. The other option is to use double chemotherapy plus bevacizumab, since anti-EGFR seems to have modest activity in these patients. Only a small percentage of patients who experience failure of this first-line treatment receive second-line treatment. Monotherapy with BRAF inhibitors has failed in this setting, and different combinations have also been tested. Using the rationale that BRAF inhibitor monotherapy fails due to feedback activation of the EGFR pathway, BRAF inhibitors have been combined with anti-EGFR agents plus or minus MEK inhibitors; however, the results did not live up to the hopes raised by the concept. To date, the best results in second-line treatment have been obtained with a combination of vemurafenib, cetuximab, and irinotecan. Despite these advances, further improvements are needed.

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Section: Treatment Of Braf-mutant Tumorsmentioning

confidence: 99%

Molecular targeted therapy of BRAF-mutant colorectal cancer

et al. 2019

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Dendritic Cell-Derived Exosomes Driven Drug Co-Delivery Biomimetic Nanosystem for Effective Combination of Malignant Melanoma Immunotherapy and Gene Therapy

Lin¹,

Huang²,

Li³

et al. 2023

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Purpose Malignant melanoma (MM), the most lethal skin cancer, is highly invasive and metastatic. These qualities are related to not only genetic mutations in MM itself but also the interaction of MM cells with the immune system and microenvironment. This study aimed to construct a combined immunotherapy and gene therapy drug delivery system for the effective treatment of MM. Methods Mature dendritic cell (mDC) exosomes (mDexos) with immune induction functions were used as carriers. BRAF siRNA (siBRAF) with the ability to silence mutated BRAF in MM was encapsulated in mDexos by electroporation to construct a biomimetic nanosystem for the codelivery of immunotherapy and gene therapy drugs (siBRAF-mDexos) to the MM microenvironment. Then, we investigated the nanosystem’s serum stability and biocompatibility, uptake efficiency in mouse melanoma cells (B16-F10 cells), cytotoxicity against B16-F10 cells and inhibitory effect on BRAF expression. Furthermore, we evaluated its antimelanoma activity and safety in vivo. Results SiBRAF-mDexos were nanosized. Compared to siBRAF, siBRAF-mDexos displayed significantly increased serum stability, biocompatibility, uptake efficiency in B16-F10 cells, and cytotoxicity to B16-F10 melanoma cells; they also had a significantly greater inhibitory effect on BRAF expression and induced T-lymphocyte proliferation. Moreover, compared with siBRAF, siBRAF-mDexos showed significantly enhanced anti-MM activity and a high level of safety in vivo. Conclusion The study suggests that the siBRAF-mDexo biomimetic drug codelivery system can be used to effectively treat MM, which provides a new strategy for combined gene therapy and immunotherapy for MM.

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What is the prognostic impact of BRAF mutation in patients undergoing resection of colorectal liver metastases? Results of nationwide intergroup (ACHBT, FRENCH, AGEO) cohort of 249 patients.

Cited by 2 publications

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Molecular targeted therapy of BRAF-mutant colorectal cancer

Molecular targeted therapy of BRAF-mutant colorectal cancer

Dendritic Cell-Derived Exosomes Driven Drug Co-Delivery Biomimetic Nanosystem for Effective Combination of Malignant Melanoma Immunotherapy and Gene Therapy

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