||5R21CA209566-03 Interpret this number
||Ohio State University
||Dietary Fats, Mitochondrial Function and Muscle Health in Cancer Patients
Thanks to early detection and treatment, women can expect excellent survival after an initial diagnosis of
breast cancer. However, widely-used treatments such as anthracycline chemotherapy (AC) incur
significant morbidity and mortality via effects on skeletal and cardiac muscle. Cardiomyopathy affects 1 in
5 breast cancer survivors within 3 years of diagnosis and over half of breast cancer survivors develop
symptoms attributable to skeletal muscle weakness. A key mechanism underlying these toxicities
involves adverse effects in mitochondria on cardiolipin, an essential phospholipid that forms the inner
mitochondrial membrane and supports ATP synthesis. Anthracyclines (AC) in particular bind cardiolipin,
rendering it unavailable to support proteins involved with the electron transport chain. Disturbing
mitochondrial cardiolipin reduces ATP production in both skeletal and cardiac muscle. However, there
has been no study to date in breast cancer patients showing that decreased cardiolipin levels are
associated with the decline of structure and function of skeletal and cardiac muscle also diminishes from
chemotherapy treatment. Our team has generated ground-breaking preliminary data in breast cancer
survivors showing that cardiolipin levels, via a novel and robust assay in peripheral blood lymphocytes,
predict reduced muscle mass in breast cancer survivors. We have also implemented direct measurement
of cardiac function and structure using cardiac magnetic resonance (CMR) imaging and assessment of
mitochondrial function in skeletal muscle using the well-established technique of 31-phosphorus magnetic
resonance spectroscopy (31P-MRS). We recently completed a prospective study using cardiac strain
measurement, a highly sensitive magnetic resonance-based biomarker of subclinical cardiac dysfunction,
showing early decline in LV strain after anthracycline chemotherapy in breast cancer patients. We also
have the ability to analyze cardiolipin profiles and lipids important to cardiolipin function. We are now
poised to conduct an essential study of skeletal and cardiac muscle integrated with careful clinical
assessment in breast cancer survivors receiving AC towards a long-term goal of targeting cardiolipin to
reduce morbidity and mortality. Aim 1: Measure the relationships among skeletal muscle, cardiac muscle
and cardiolipin status in breast cancer survivors. Aim 2: Assess longitudinal chemotherapy-induced
changes in cardiolipin composition, skeletal muscle and cardiac muscle.
Altered Plasma Fatty Acid Abundance Is Associated with Cachexia in Treatment-Naïve Pancreatic Cancer.
, Hart P.A.
, Belury M.A.
, Crowe O.
, Cole R.M.
, Pita Grisanti V.
, Badi N.
, Liva S.
, Hinton A.
, Coss C.
, et al.
Cells, 2022-03-07; 11(5), .