There is a huge variety of nucleotide substitutions that activate RAS. The search for new "universal" drugs for the RAS pathway that either interfere with RAS upregulation upstream in the signaling pathway or offset the consequences of RAS activation is important for improving therapeutic outcomes for patients with refractory malignancies.
The use of leflunomide or the combination of MEK inhibitor + hydroxychloroquine ± bevacizumab is promising for patients with mutations in RAS cascade genes who have failed all existing treatment standards.
Patient is able to provide informed consent and sign approved consent forms to participate in the study.
Patient age is at least 18 years old.
Performance status Eastern Cooperative Oncology Group (ECOG) 0-2.
Histologically confirmed metastatic metastatic disease stage 4.
Age over 85 years.
Рresence of acute or active chronic infections.
Impaired renal and hepatic function; - left ventricular ejection fraction (LVEF) < 45%
Known history of acute or chronic hepatitis B or C due to known potential hepatotoxicity of leflunomide.