HDAC inhibitors can be used to potentially reverse targeted drug resistance.

I don't know if my friends, who often pay attention to me, have noticed that I recently wrote two articles about anti-angiogenesmic targeting drugs, one of which is a soft tissue sarcoma patient with a TP53 mutation that promises better results when using anti-angiogenesid target drugs.
The other is the anti-angiogenic drug pazopani, which has a better inhibitory effect on the treatment of patients with malignant tumors with six hot mutations in TP53, especially colorectal cancer and sarcoma.
The relationship between anti-angiogenesis drugs and TP53 is mentioned in both articles, the internal logic of which is that TP53 can be used as an indicator of antivascular targeted drugs, because the state of TP53 can be used as an independent predictive indicator of VEGF.
is that Volino can enhance the efficacy of anti-angiogenesin drugs, especially in patients with TP53, six mutants.
Because antiangiogenic drugs are the most widely used and commonly used treatment for a class of malignant tumors, I continue this topic today, saying that the following ebigenestic drugs in the fight against angiogenescular therapy.
with epigenetic drugs Volino, Ebesta, sidabenamine reverse anti-angiogenesis drug resistance, introduced under anti-angiogenesis target in the morning or evening drug resistance if resolved.
Anti-angiogenescular resistance Long-lasting reactions are rare in the treatment of tyrosine kinase inhibitors of antivascular endotinogen receptors (VEGFR) including atrotine, including atrotine and apatini. , after a period of use, or sooner or later will produce drug resistance caused tumor progression, causing this part of the cause is mainly due to, tumors, especially angiogenescular tumors consisting of vascular endoder cells, driven by VEGF, can adapt to the presence of anti-angiogenesial targeted drugs, thereby functionally circumventing the therapeutic effect. One of the mechanisms involved in
is hypoxic-driven hibulin deacetylase (HDAC), a direct regulation of VEGF expression-promoting angiogenesin factors, hypoxia-inducing factor HIF-1 alpha over-expression and post-translation stabilization.
HDAC inhibition reduced HIP-1 alpha protein expression under hypoxia conditions, and when HDAC inhibitors were used, resistance was reversed when anti-angiogenescular treated tumor cells were found.
this is similar to what other HDAC inhibitors, Volino and Abbes, have observed.
pharmacoetic analysis supports the speculative mechanism of downward expression through egesmologically mediated HIF-1 alpha and VEGF.
reduction in VEGF levels (a direct transcription target for HIF-1 alpha) was significantly associated with the induction of PBMC hibulin acetylation, an effective biomarker of HDAC inhibition.
HDAC2 is a central HDAC enzyme that directly regulates VEGF expression by binding to the launcher.
inhibits HDAC2 inhibits VEGF expression and angiogenesy.
contrast, HDAC6 is a microscellular-related cytoste HDAC that does not affect the expression of VEGF or HIF-1 alpha.
mechanisms of cell location and function may explain why the expression of HDAC2, rather than HDAC6, is closely related to long-lasting therapeutic responses in the current study.
test process and results Test design dosage and dosage time: Pazopani 800 mg per day, Abestaz 45 mg / body meter, twice a day, 4 days and 7 days, 3 weeks and 4 weeks, respectively.
efficacy analysis in 51 patients, 43 cases were of reference significance, in the single-drug treatment of pazopani, the progression of the disease in 10 patients, 7 (70%) of the participants in the study showed tumor receding.
Of the 28 patients who had used one or more VEGF targeted therapy advances, 19 (68 percent) showed tumor receding in joint study therapy, including 6 patients with objective tumor responses (21 percent).
response was quite long-lasting, with a mid-response time of 9.1 months, with eight patients experiencing stable or ongoing treatment of the tumor for more than 12 months, including five who were still being studied.
most patients with a long-lasting response experienced disease progression in previous VEGF targeted therapy.
one of these patients lasted more than 3.5 years.
the patient developed the disease on the first line of Shonitoni and then switched to other back-line drugs targeted at VEGF, including Sorafini, Pazopani and Bevamedin.
immediately after re-using Papopani and Ebes, the tumor response developed and continued partially for 3.5 years.
In practical application, the anti-angiogenesic targeting of VEGF is an important means of many malignant tumor treatment, and it is also the way that many people expect to achieve the survival goal of band tumor, but the existence of this kind of drug resistance is always difficult to overcome.
in this study, it was initially explored and verified that the use of empirective modifications inhibited by HDAC may provide a means of regaining the response and reverse resistance of solid tumors to pazopani.
especially in patients with angioscular sarcoma or angioderma, because the tumor itself is supported by the proliferation of the endogenus.
In this study, the persistence of tumor recession in 70% of patients with anti-VEGF resistance showed that the therapeutic effect exceeded the effectiveness of single-drug antivascular targeting drugs such as pazopani and supported the potential of HDAC inhibitors Volino and Abes as antiangiogenic treatment resistance in some patients.
but this study does not support HDAC's single-drug treatment, the HDAC inhibitory effect in combined treatment coupled with a sustained antiveGF pathway to restore the therapeutic response.
further testing is needed to determine whether HDAC inhibition monodies can enhance the response to pazolepani or reverse resistance.
in summary, adding HDAC inhibitors volinoto or abstos to pazopani or other anti-angiogenesis drugs has good tolerance and produces an amazingly long-lasting response.
is intended to introduce and popular science malignancies frontier research information, explain the scientific principles behind and test results, do not promote drugs and treatment options.
follow the advice or guidance of a doctor or professional.
.