The road to kras Iron Throne is the domestic leader in Gakos.

Text . . . The Mercure RAS gene mutation is a genetic driver of a variety of cancer types, including colorectal cancer, pancreatic catheter gland cancer (PDAC), lung adenocarcinoma (LUAD; a subtype of non-small cell lung cancer (NSCLC), melanoma, and certain blood system cancers. I.T. I.B.A., the isomers (KRAS, NRAS, or HRAS), ciphers, and frequencies of the
1 organizations distributed rasa mutations vary by tissue type.
for example, a large percentage of LUAD (32%), PDAC (86%) and CRC (41%) are driven by KRAS mutations, in which the KRAS mutation occurs primarily in the 12th-digit cryptose.
by contrast, 29% of melanomas are driven by NRAS mutations, which, unlike KRAS, occur in crypto61.
hrAS mutations occur less frequently than KRAS or NRAS mutations, but a small fraction of head and neck squamous cell carcinoma (HNSCC; 5%) and bladder cancer (6%) are driven by HRAS mutations, which occur in the cipher12 or 61.
as shown in Figure 1 below.
Figure 1. Frequency and distribution of RAS gene mutations in human cancers -a. The distribution of RAS subtypes (KRAS, NRAS and HRAS) mutations in different tumor types and the frequency of RAS subtype mutations in each tumor type; The percentage of KRAS mutations in the 12th cryptosome of RAS common mutation tissue, and the percentage of NRAS mutations of the 61st cryptoon of melanoma, the biochemical properties of the 2 mutant RAS usually, the mutation of the crypto-12 will destroy the GTPase activity of ras, thereby reducing the hydrolysis rate of the GTP, so the mutant protein accumulates in the state of GTP binding.
the 61-bit crypt mutation accelerates the speed of GDP-GTP switching, while reducing the hydrolysis speed of GTP, so the RAS mutant of the 61-bit crypto-code will also accumulate in the state of GTP binding, as shown in Figure 2 below.
THE COMBINED RAS OF GTP ACTIVATES THE DOWNSTREAM EFFECT PATHWAY AND PROMOTES CELL PROLIFERATION, MOST NOTABLY THE MAPK AND PI3K PATHWAYs.
Figure 2. Overview of the general biochemical interference caused by hydrolysis and bird's slug exchange caused by the cryptox 12 or 61 mutations. The AMG-5102019WCLC meeting revealed data on 23 assessable patients with an total efficiency of 48%.
of 13 patients who received a target dose of 960 mg, 7 were partially remissioned (PR), 6 were stable (SD), and disease control rates were 100%.
safety and tolerance are good.
specific results include security figures 3, 4, and 5 below.
Figure 3. Assessable NSCLC patients with baseline post-tumor data (N-22), Source: Public Information Collating Figure 4. Recommended to Phase II Dose 960 mg AMG510 Current Efficacy, Source: Public Information Finishing Figure 5. Summary of adverse events (AEs) in Patients with AMG-510 Source: Public Information Collating It is important to note that AMG510 is much less active in colorectal cancer: only 1 in 12 patients had PR and 10 had SD.
B. MRTX849 data from the top 12 patients with advanced lung and colorectal cancer (17 in the first phase trial) showed that 40% of patients had significantly reduced tumor size.
3 patients with advanced lung cancer had partial reactions (tumor volume decreased by 30% or more).
one of the patients with advanced colorectal cancer who was assessed had a partial response.
all patients who responded received the highest dose used in the dose range study (twice a day at 600 mg).
reported that most of the side effects of MRTX-849 were mild, including diarrhea and nausea; The
results are shown in Figures 6 and 7 below.
Figure 6. MRTX849 is currently publicly available for efficacy, data source: Public Information Collating Chart 7. Summary of adverse events (AEs) in patients with MRTX849,Source:Public Information Collated C. Other small molecular inhibitors in the clinical phase Table 1. Other small molecular inhibitors in clinical phase Summary Source: Drug Data Rs-3248 is a new generation of KRAS G12C inhibitors developed on the basis of ARS-1620.
May 2019, Wellspring announced that the FDA had approved THE IND application for ARS-3248.
Janssen is solely responsible for the clinical development of the compound and registered JNJ-74699157 (ARS-3248) in clinical trials on July 26 to conduct a phase I trial (NCT04006301) in the patient with a positive advanced stage solid tumor in the KRASG12C group.
September 29, 2019, THE SMALL MOLECULE ORAL ANTI-TUMOR DRUG JAB-3312, DEVELOPED BY THE DOMESTIC COMPANY GACOS INDEPENDENTLY, WITH GLOBAL INTELLECTUAL PROPERTY RIGHTS, WAS GRANTED CLINICAL LICENSE IN CHINA.
JAB-3312 will be used to treat patients with genotype abnormally active tumors such as KRAS G12, BRAFClass3, NF1LoF, and RTK mutations, amplification or resection, including, but not limited to, non-small cell lung cancer, colorectal cancer, pancreatic cancer, esophageal scale cancer, head and neck squamous cancer.
BI1701963 inhibits KRAS by binding to SOS1.
by swapping RAS-bound GDP for GTP, SOS1 can help activate KRAS. Selective inhibition of SOS1 in
is a therapeutic concept that enables KRAS blocking regardless of the type of KRAS mutation.
preclinical studies show that pan-KRAS inhibitors inhibit the growth of multiple G12 and G13 KRAS gene mutant tumors (the most commonly affected protein residues).
D. combination therapy is also under development for both upstream and downstream targets of the KRAS and KRAS signaling pathways, as detailed in Table 2.
Table 2. The combined therapeutic sources of clinical development of KRAS are included in the drug-based database, and the public information collection researchers combined KRAS inhibitors with CDK, EGFR, Tubulin, MEK and other inhibitors, and looked forward to therapeutic synergies in the body.
4 current problem I. alleles gene-specific inhibitors may have limited efficacy as monotherapy.
the largest anti-tumor effects need to be combined with other inhibitors, it can be challenging to determine which combination strategy works best in patients.
II. Tumor type can significantly affect response rate. early data from the
AMG510 trial showed that colorectal cancer was more difficult to treat than LUAD, suggesting that colorectal cancer would require combination therapy. Treatment of colorectal cancer
is particularly challenging.
III. Historically, combination therapy has been toxic and inpoor safety.
However, the toxicity of the lack of dose limit observed by AMG510 is encouraging, and mutation-specific therapy should have limited non-target effects.
alleles of gene-specific inhibitors (low toxic) can be used in combination with other more toxic inhibitors without the problem of combining two toxic compounds observed when used in combination with PI3K and MEK inhibitors.
IV. As the treatment of RAS-driven tumors becomes more personalized, it is necessary to evaluate the potential resistance mechanisms of peer-specific inhibition.
5 concludes that KRAS-G12C alleles will change the treatment pattern of RAS-driven tumors.
these inhibitors are expected to become the first FDA-approved drug to treat RAS-mutant tumors and will be used to treat refractive cancers driven by mutant RAS, such as PDAC, CRC, and LUAD.
target ingasomuted RAS protein is the best way to treat RAS-mutant tumors.
Despite these problems, the expected success of the first KRAS inhibitor is also exciting, and we look forward to further data release in the future and the early market launch of the well-behaved KRAS inhibitor for the benefit of patients.
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