Resistance to certain KRAS G12C inhibitors can result from the buildup of active, GTP-bound RAS, which can increase tumor growth in cancer patients. Therefore, effectively blocking active RAS becomes crucial. In a recent study, researchers led by Ferdinandos Skoulidis, M.D., Ph.D., and Haniel Araujo, M.D., evaluated the antitumor effects of a new class of inhibitors that target the active form of RAS proteins: RMC-7977, a pan-RAS inhibitor of KRAS/HRAS/NRAS, and RMC-4998, a RAS G12C-selective inhibitor. Active RAS...

The University of Texas MD Anderson Cancer Center and Replay announced that the Food & Drug Administration (FDA) has issued a ‘safe to proceed’ for the Investigational New Drug (IND) application for PRAME TCR/IL-15 NK (SY-307), an engineered T cell receptor natural killer (TCR NK) cell therapy for relapsed/refractory myeloid malignancies. MD Anderson is the IND sponsor.   PRAME TCR/IL-15 NK (SY-307) is being developed by Syena, an oncology-focused product company launched by Replay and MD Anderson based on the...

Rare cancers are difficult to study in a clinical trial setting due to the relatively small number of patients. Two studies recently published in The Lancet Oncology examined the use of cabozantinib, an antiangiogenic multi-tyrosine kinase inhibitor, on two rare cancers: adrenocortical carcinoma, an endocrine cancer, and metastatic phaeochromocytomas and paragangliomas (MPPGs), both neuroendocrine tumors. Notably, these two cancers have just one FDA approved treatment each. The studies highlight the therapeutic potential of cabozantinib in combination with other therapies...

One of the most frequently mutated epigenetic factors in cancer is a large protein complex called SWI/SNF, which regulates gene transcription and is crucial for proper cell differentiation. An important question has been how SWI/SNF is recruited to cell-type-specific regions of DNA, called enhancers. Researchers led by Blaine Bartholomew, Ph.D., found a special class of non-coding enhancer RNA (eRNA) that recruits SWI/SNF to cell-type specific enhancers involved in the switch from undifferentiated to differentiated cells. By...

Pancreatic cancer is notoriously aggressive and difficult to treat, underscoring the need for more effective therapeutic targets. Research led by Jie Fu, Ph.D., Jianhua Ling, Ph.D., and Paul Chiao, Ph.D., previously showed that apoptosis, or cell death, resistance in KRAS G12D-mutant pancreatic cancer was accelerated by deleting the Plk3 tumor suppressor, but the regulatory mechanism of Plk3 activation remains unknown.   To provide further insights, the researchers examined the role of Plk3 in KRAS G12D-mutant pancreatic cancer models. They...

The independent contribution of routine radiology scans in predicting recurrence in patients with non-small cell lung cancer (NSCLC) is relatively unexplored. In a new study of 394 NSCLC patients, led by Jia Wu, Ph.D., Tina Cascone M.D., Ph.D., and Jianjun Zhang, M.D., Ph.D., researchers developed a proof-of-concept imaging framework to stratify patients into three clinically meaningful subtypes with distinct prognoses.   These subtypes add to the prognostic information obtained from clinicopathological risk factors and ctDNA alone, and they could potentially serve...

Researchers at The University of Texas MD Anderson Cancer Center showed that altering the sequence of breast cancer treatment to administer radiation before mastectomy allowed for concurrent breast reconstruction surgery, which reduced the number of operations required, minimized treatment delays, and improved patient satisfaction.   The Phase II trial results evaluated 49 patients who received radiation therapy followed by mastectomy with immediate breast reconstruction. There were no complete flap losses or disease recurrences at a...

Galectin-3 (GAL3), which regulates cell proliferation and the function of various immune cell populations, is highly expressed by myeloid and pancreatic cancer cells. However, its role in the pancreatic tumor microenvironment remains unclear. To provide further insights, researchers led by Yang Chen, Ph.D., generated in vivo models of pancreatic cancer with GAL3 genetically deleted in both cancer and myeloid cells. Deleting GAL3 inhibited pancreatic cancer progression and prolonged survival in these models. Single-cell sequencing revealed that GAL3 deletion enriched antitumor...

Patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy have limited therapeutic options. Previous research suggests hypomethylating agents combined with venetoclax are effective for this group, but the hypomethylating agent must be given via parenteral administration or intravenous injection outside of the digestive tract. In a Phase II study, researchers led by Farhad Ravandi, M.D., and Alexandre Bazinet, M.D., evaluated an oral combination of decitabine and cedazuridine (ASTX727) plus venetoclax in 62...

Osteoclast cells are responsible for the resorption of bone structure and minerals, and their dysregulation is associated with osteoporosis, or decreased bone mineral density. Building upon previous work showing that MALAT1, a long noncoding RNA (lncRNA), suppresses breast cancer metastasis, Li Ma, Ph.D., and colleagues noted that a specific mutation in MALAT1 was associated with low bone mineral density and sought to determine the role of MALAT1 alternations in bone diseases. MALAT1 deficiency led to osteoporosis and more severe bone metastases of...