Breast cancer is the most common cancer in women. Hormone therapy is the major treatment option for patients with estrogen receptor-positive (ER+) and Her2-negative (Her2-) breast cancer.
Category Archives: ACT Genomics
In an expansion cohort of a phase I CHRYSALIS study, the RP2CD (recommended phase 2 combination dose) of amivantamab antibody combined with 3rd generation EGFR TKI lazertinib to exam patients in osimertinib resistant(n=45) or treatment-naïve(n=20) EGFR-positive (exon 19 deletions and L858R) NSCLCs. In osimertinib resistant group, the objective response rate(ORR) was 36% with one patient complete response, response was seen irrespective of first or second lines used osimertinib.
ERBB2 exon 20 insertion accounts for 2-3% of the total mutations of non-small cell lung cancer. However, there is still an unmet need for treating patients with this kind of mutation. The phase 2 ZENITH20 trial is aimed to study the activity of poziotinib in NSCLC patients with either an EGFR exon 20 insertion or an ERBB2 exon 20 insertion.
Urothelial carcinoma (UC) is one of the malignant diseases with a poor five-year survival rate. Platinum-based regimen is the major treatment option for patients with UC. Recently, immune checkpoint inhibitors had been demonstrated anti-tumor activity in UC. Avelumab is an anti–PD-L1 antibody that has been approved with first-line maintenance treatment in UC followed the phase 3 JAVELIN Bladder 100 trial.
ALK gene fusion occurs in approximately 3%-5% of NSCLC patients. Currently, there are 5 FDA approved tyrosine kinase inhibitors (TKI): crizotinib (first generation), ceritinib, alectinib, brigatinib (second generation), lorlatinib (third generation).
Currently, olaparib has been approved by the US. FDA for treating HER2-negative breast cancer patients who had a germline BRCA mutation. In phase I/II MEDIOLA study, the activity of olaparib in combined with durvalumab in various solid tumors were examined.
Gene fusion is one of the tumourigenic mechanisms as a drug target. For example, ALK, ROS1, RET, and NTRK1/2/3 gene fusions are identified as the druggable mutation across solid tumors. NRG1 gene fusion is an other druggable fusion, which activates ErbB signal pathways and promotes tumor growth. Drugs for blocking ErbB signal pathways are considered as treatment options for cancers with NRG1 gene fusion.
ESR1 mutations have been reported that will contribute to the resistance of the aromatase inhibitor (AI) in HR+ breast cancer patients in several past studies. However, the role of ESR1 mutation remains unknown when the AI is combined with the CDK4/6 inhibitors. In phase 3 PADA-1 study, 33 of the 1017 enrolled patients (3.2%) harbored an ESR1 mutation before receiving the 1st-line AI plus palbociclib.
Brain tumors are rare but difficult to manage. Glioma is the most common type of tumor in the brain that begins in glial cells. IDH1/2 genes are important genes in both glioma classification and targeted therapy treatment. Adult diffuse gliomas of grade II and III are classified as low-grade gliomas based on the histology and molecular biomarkers by the 2016 World Health Organization (WHO) classification.
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