Publications by authors named "J E Bisi"
Unlabelled: Cyclin-dependent kinase 2 (CDK2) is thought to play an important role in driving proliferation of certain cancers, including those harboring CCNE1 amplification and breast cancers that have acquired resistance to CDK4/6 inhibitors (CDK4/6i). The precise impact of pharmacologic inhibition of CDK2 is not known due to the lack of selective CDK2 inhibitors. Here we describe INX-315, a novel and potent CDK2 inhibitor with high selectivity over other CDK family members.
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- The combination of palbociclib and fulvestrant is effective for treating ER-positive breast cancer, but fulvestrant's poor properties necessitate monthly injections, limiting its effectiveness.
- G1T48 is a new orally available small molecule that acts as an antagonist to estrogen receptors and has been shown to inhibit tumor growth in various breast cancer models.
- In studies, G1T48 demonstrated strong antitumor activity, especially in resistant cancer types, and works even better when paired with the CDK4/6 inhibitor lerociclib.
Article Synopsis
- Immune checkpoint blockade, like PD-1 receptor antibodies, can lead to significant tumor reductions, but researchers are looking for ways to boost their effectiveness.
- A study found that using small-molecule inhibitors of CDK4/6 can enhance T-cell activation and tumor response, even while reducing overall T-cell proliferation.
- The findings suggest that combining CDK4/6 inhibitors with existing immunotherapy treatments could improve cancer treatment outcomes, emphasizing the need for innovative strategies to augment immunotherapy efficacy.
Conventional cytotoxic chemotherapy is highly effective in certain cancers but causes dose-limiting damage to normal proliferating cells, especially hematopoietic stem and progenitor cells (HSPCs). Serial exposure to cytotoxics causes a long-term hematopoietic compromise ("exhaustion"), which limits the use of chemotherapy and success of cancer therapy. We show that the coadministration of G1T28 (trilaciclib), which is a small-molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), contemporaneously with cytotoxic chemotherapy protects murine hematopoietic stem cells (HSCs) from chemotherapy-induced exhaustion in a serial 5-fluorouracil treatment model.
View Article and Find Full Text PDFInhibition of the p16INK4a/cyclin D/CDK4/6/RB pathway is an effective therapeutic strategy for the treatment of estrogen receptor positive (ER+) breast cancer. Although efficacious, current treatment regimens require a dosing holiday due to severe neutropenia potentially leading to an increased risk of infections, as well as tumor regrowth and emergence of drug resistance. Therefore, a next generation CDK4/6 inhibitor that can inhibit proliferation of CDK4/6-dependent tumors while minimizing neutropenia could reduce both the need for treatment holidays and the risk of inducing drug resistance.
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