Immune Checkpoint Inhibitors in Cancer Therapy-How to Overcome Drug Resistance?

Immune checkpoint inhibitors (ICIs), antagonists used to remove tumor suppression of immune cells, have been widely used in clinical settings. Their high antitumor effect makes them crucial for treating cancer after surgery, radiotherapy, chemotherapy, and targeted therapy. However, with the advent of ICIs and their use by a large number of patients, more clinical data have gradually shown that some cancer patients still have resistance to ICI treatment, which makes some patients unable to benefit from their antitumor effect.

Long non-coding RNAs as targets for immunosuppressive drug teriflunomide in anti-cancer potential for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer. Because of the relatively chemotherapy-refractory nature of HCC and significant potential poor hepatic reserve, chemotherapy has not been used consistently in the treatment of HCC. Effective new drugs for HCC are urgently needed.

Design, synthesis, and evaluation of a series of novel phenylpropanoic acid derivatives agonists for the FFA1.

Free fatty acid 1 (FFA1/GPR40) has attracted extensive attention as a novel target for the treatment of type 2 diabetes for its role in the enhancement of insulin secretion with glucose dependency. Aiming to develop novel potent FFA1 agonists, a new series of phenylpropionic acid derivatives were designed and synthesized on the basis of the modification of chemical cement of TAK-875, AMG-837, and LY2881835. Among them, most promising compounds 7, 14, and 15 were obtained with EC values of 82, 79, and 88 nM, exhibiting a powerful agonistic activity compared to TAK-875 (95.

Treatment of hypertension by increasing impaired endothelial TRPV4-KCa2.3 interaction.

The currently available antihypertensive agents have undesirable adverse effects due to systemically altering target activity including receptors, channels, and enzymes. These effects, such as loss of potassium ions induced by diuretics, bronchospasm by beta-blockers, constipation by Ca channel blockers, and dry cough by ACEI, lead to non-compliance with therapies (Moser, 1990). Here, based on new hypertension mechanisms, we explored a new antihypertensive approach.

Teriflunomide, an immunomodulatory drug, exerts anticancer activity in triple negative breast cancer cells.

Triple-negative breast cancer (TNBC) is defined as a group of primary breast cancers lacking expression of estrogen, progesterone, and human epidermal growth factor receptor-2 (HER-2) receptors, characterized by higher relapse rate and lower survival compared with other subtypes. Due to lack of identified targets and molecular heterogeneity, conventional chemotherapy is the only available option for treatment of TNBC, but non-discordant positive therapeutic efficacy could not be achieved. Here, we demonstrated that these TNBC cells were sensitive to teriflunomide, which was a well-known immunomodulatory drug for treatment of relapsing multiple sclerosis (MS).