Br J Cancer: ADI-PEG20 combined with cisplatin in the treatment of metastatic malignant solid tumors

Previous studies have shown that cancer cells may overcome the energy required for rapid proliferation through metabolic reprogramming.
The abnormal metabolic pathways produced in these cancer cells may become potential therapeutic targets for cancer treatment.

Cancer cells may undergo metabolic reprogramming to overcome the energy required for their rapid proliferation.
The abnormal metabolic pathways produced in these cancer cells may become potential therapeutic targets for cancer treatment.
Cancer cells may undergo metabolic reprogramming to overcome the energy required for their rapid proliferation.
The abnormal metabolic pathways produced in these cancer cells may become potential therapeutic targets for cancer treatment.

Arginine is a semi-essential amino acid, which can be involved in the regulation of a variety of cellular processes such as cell signaling, cell proliferation, vascular relaxation and hormone synthesis.
Argininealso plays a vital role in the regulation of the immune system.

Arginine is a semi-essential amino acid, which can be involved in the regulation of a variety of cellular processes such as cell signaling, cell proliferation, vascular relaxation and hormone synthesis.
Arginine is a semi-essential amino acid, which can be involved in the regulation of a variety of cellular processes such as cell signaling, cell proliferation, vascular relaxation and hormone synthesis.
Vascular Immunity

Most normal human cells synthesize arginine through two key enzymes.

However, some cancer cells lack the necessary enzymatic pathways, so arginine must be obtained from the blood to grow and survive normally.

Previous studies have shown that arginine depletion can interfere with pyrimidine metabolism and DNA damage repair pathways.

ADI-PEG20 combined with cisplatin therapy can enhance the cytotoxicity of arginine auxotrophy.

The single-center phase 1 clinical trial used a 3+3 dose escalation scheme to evaluate the safety and tolerability of ADI-PEG20 and determine the recommended phase 2 dose (RP2D).

Survival curve analysis of the combined treatment cohort

Researchers recruited 99 patients with metastatic ASS1 (arginine succinate synthase 1)-deficient malignancies.

The results showed that no dose-limiting toxic effects or treatment-related deaths were observed.

After receiving treatment, 5% (5/99) of the patients had a partial response, and 41% of the patients were in stable condition.

The patients' median progression-free survival and overall survival were 3.

Pharmacodynamic results of the combination treatment cohort

All in all, the results of the study revealed that ADI-PEG20 and cisplatin taken at the same time have acceptable safety and have shown anti-tumor activity against metastatic ASS1-deficient solid tumors.

Therefore, it is necessary to further evaluate the effect of the treatment combination.

The ADI-PEG20 and cisplatin taken at the same time have acceptable safety and have shown anti-tumor activity against metastatic ASS1-deficient solid tumors.

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