February 2024 – Page 2

SMYD2 methyltransferase identified as driver of breast cancer metastasis

February 24, 20241 min

The majority of breast cancer deaths are linked to its metastatic spread to distant organs, but therapeutic options remain limited for certain types of aggressive breast cancer that frequently metastasize. A new study led by Pawel Mazur, Ph.D., identified the lysine methyltransferase SMYD2 as a critical regular of breast cancer metastasis. The SMYD2 enzyme acts by modifying other proteins that can induce changes in the cellular cytoskeleton. In preclinical models, inhibiting SMYD2 activity increased overall survival by blocking the...

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IDH1 inhibitor lowers antifungal medication levels in patients with AML and MDS

February 24, 20241 min

Patients with IDH1-mutated relapsed/refractory acute myeloid leukemia (AML) usually are treated with the IDH1 inhibitor ivosidenib. However, patients with AML and myelodysplastic syndromes (MDS) are at increased risk of fungal infections and are frequently given triazole antifungal medications, such as posaconazole and voriconazole. To study possible drug-drug interactions, researchers led by Caitlin Rausch, Pharm.D., and Ashley Dinh, Pharm.D., evaluated serum triazole levels in 78 samples from 31 patients receiving ivosidenib-containing therapy in combination with posaconazole and voriconazole. They discovered median triazole...

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Co-clinical trial shows potential of PDX models in early-phase clinical trials

February 24, 20242 min

Patient derived xenograft (PDX) models – which utilize tissues or cells from patients for in vivo tumor studies – are used to study antitumor activity and mechanisms of intrinsic and acquired resistance, but it is unclear how well they translate to clinical responses. To address this, researchers led by Funda Meric-Bernstam, M.D., developed PDX models in a co-clinical trial to compare against patient responses with the bispecific HER-2 targeted antibody zanidatamab. Of 36 tumors implanted, the researchers established...

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Study identifies potential therapeutic target for subset of patients with bladder cancer

February 24, 20241 min

Many patients with metastatic bladder cancer have inactivated SMARCB1, which is normally involved in DNA remodeling. The loss of SMARCB1 activates the STAT3 inflammation pathway and is a well-known biomarker of aggressive renal medullary carcinoma, suggesting that these events drive tumor growth and progression. To provide further insights, researchers led by Pavlos Msaouel, M.D., Ph.D., used lab models of bladder cancer without SMARCB1. SMARCB1 deficiency led to increased STAT3 activation as well as increased tumor growth and metastasis. The...

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