Br J Cancer: Drug resistance-related studies in patients with BRAF V600E mutant colorectal cancer

Colorectal cancer (CRC) is one of the world's major causes of cancer death, with nearly 900,000 deaths worldwide in 2018.
in the initial diagnosis, about 25 percent of patients had cancer metastasis, while 50 percent of all patients had metastasis during the disease.
about 8-15% of metastasis CRC patients carry BRAFV600E mutations, which also cause standard chemotherapy failure and poor prognostics.
braF gene encodes serine/suline protein kinase, which is part of the MAPK signal transducting path.
abnormally activated mutant BRAF is able to mediate this signal transducting path through the downstream MEK1/2 protein phosphate, and MEK1/2 is then transdated by phosphate ERK1/2 kinase, which eventually leads to transcription of the genes that drive cell proliferation and survival.
BRAFV600E mutation is the most common mutation in different types of tumors, and its protein 600th proline is replaced with glutamate.
has developed a joint therapy strategy to inhibit BRAF and EGFR in patients with BRAFV600E mutated metastatic colorectal cancer, but intrinsic and secondary resistance remains a major challenge to this treatment strategy.
the study was designed to investigate which genetic changes in patients treated with BRAF and EGFR inhibitors can cause intrinsic non-response and/or access resistance.
the study of anti-tumor activity (including optimal response and progression time and mutation characteristics) in patients and treatment groups as a cohort study focused on genetic changes in patients with BRAFV600E mutant advanced colorectal cancer treated with MAPK path pathogenic inhibitors.
researchers examined genetic changes in tumor tissue during baseline, treatment, and tumor progress.
the queue included a total of 37 patients.
researchers found that genetic changes in EGFR and PIC3CA were associated with no response in patients.
a larger portion of non-responding patients (75 percent) had at least one genetic change in a gene other than TP53, APC, or BRAF compared to drug-response patients (46 percent).
secondary drug-resistant mutations (n-16) are most commonly observed in pi3K paths (n s 6) and the subject tyrosine kinase (n s 4) and cause an increase in upstream signals.
a summary of the mutated pie charts obtained by each treatment group during treatment with MAPK inhibitors, the study showed that genetic changes in PI3K and the subject tyrosine kinase were associated with intrinsic and obtainable resistance.
by analyzing these changes, the study suggests that simultaneous or alternating use of targeted inhibitors may improve the duration of the drug.
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