Clonal hematopoiesis of indeterminate potential is associated with increased risk of immune checkpoint inhibitor myocarditis in a prospective study of a cardio-oncology cohort.

Background: Clonal hematopoiesis of indeterminate potential (CHIP) has been shown to increase all-cause mortality and risk of cardiomyopathy in patients with solid malignancies. CHIP has also been shown to increase T cell activation in heart failure patients. It is unclear whether CHIP can affect the risk of immune checkpoint inhibitor (ICI) myocarditis in patients with cancer treated with immunotherapy.

Targeting the PI3K/AKT/mTOR pathway in epithelial ovarian cancer, therapeutic treatment options for platinum-resistant ovarian cancer.

The survival rates for women with ovarian cancer have shown scant improvement in recent years, with a 5-year survival rate of less than 40% for women diagnosed with advanced ovarian cancer. High-grade serous ovarian cancer (HGSOC) is the most lethal subtype where the majority of women develop recurrent disease and chemotherapy resistance, despite over 70%-80% of patients initially responding to platinum-based chemotherapy. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway regulates many vital processes such as cell growth, survival and metabolism.

FOXA1 is a determinant of drug resistance in breast cancer cells.

Purpose: Breast cancer is one of the most commonly diagnosed cancers in women. Five subtypes of breast cancer differ in their genetic expression profiles and carry different prognostic values, with no treatments available for some types, such as triple-negative, due to the absence of genetic signatures that could otherwise be targeted by molecular therapies. Although endocrine treatments are largely successful for estrogen receptor (ER)-positive cancers, a significant proportion of patients with metastatic tumors fail to respond and acquire resistance to therapy.

mA Modification Prevents Formation of Endogenous Double-Stranded RNAs and Deleterious Innate Immune Responses during Hematopoietic Development.

N-methyladenosine (mA) is the most abundant RNA modification, but little is known about its role in mammalian hematopoietic development. Here, we show that conditional deletion of the mA writer METTL3 in murine fetal liver resulted in hematopoietic failure and perinatal lethality. Loss of METTL3 and mA activated an aberrant innate immune response, mediated by the formation of endogenous double-stranded RNAs (dsRNAs).

From clonal hematopoiesis to myeloid leukemia and what happens in between: Will improved understanding lead to new therapeutic and preventive opportunities?

Clonal hematopoiesis (CH) as defined by the presence of somatic mutations in genes associated with myeloid neoplasms (MN) is common in healthy elderly individuals and does not necessarily constitute a premalignant state. Several acronyms (idiopathic cytopenia of undetermined significance [ICUS], clonal cytopenia of undetermined significance [CCUS], CH of indeterminate potential [CHIP]) related to CH have been coined to describe patients who do not meet the diagnostic criteria for other hematologic disorders. CHIP carries an annual progression rate to MN of 0.