An update on promising agents for the treatment of cancer cachexia

Madeddu, Clelia; Mantovani, Giovanni

doi:10.1097/spc.0b013e3283311c6f

Cited by 19 publications

(13 citation statements)

References 26 publications

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“…No grade 3 or 4 toxicities were reported. xci COX-2 inhibition is currently one of the more promising areas of CIC research as this medical therapy directly targets the inflammatory APR of CIC and has shown to be well-tolerated with minimal side-effects.…”

Section: Multi-modality Therapymentioning

confidence: 99%

Nutritional Interventions for Cancer-Induced Cachexia

Gullett¹,

Mazurak²,

Hebbar³

et al. 2011

Current Problems in Cancer

104

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Cancer-induced cachexia remains a significant cause of morbidity and mortality in cancer treatment. Cancer research and development continues at an aggressive pace and yet a degree of cancer-induced cachexia is experienced by up to 80% of advanced stage cancer patients. Unfortunately, there are no established treatment regimens for this condition. Weight loss and fatigue consistently appear in patient oncologic histories and progress notes. However, few oncologists fully understand the pathologic mechanisms causing cachexia resulting in well-meaning advice to increase caloric intake with minimal results. Our goal is to describe the pathologic basis of cancer-induced cachexia and to detail accompanying metabolic derangements. Understanding the causes of cachexia sheds light on the subsequent need for multi-modality therapy including clinical intervention with specialized nutrition support, drug therapy, lifestyle and diet changes. In addition to nutrition support modalities, practicing oncologists may prescribe medical therapies designed to increase body weight and lean body mass, including megestrol acetate, tetrahydrocannibinol, oxandrolone, and non-steroidal anti-inflammatory drugs. A variety of experimental therapies are also being investigated for cancer-induced cachexia including tumor necrosis factor-alpha inhibitors and ghrelin infusions. We review the available data to support nutrition-oriented interventions in cancer-induced cachexia, including omega-3 fatty acids, amino-acid loading/protein supplementation, parenteral and enteral nutrition support, and food-derived compounds such as curcumin, reservatrol, and pomegranate.

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Section: Multi-modality Therapymentioning

confidence: 99%

Nutritional Interventions for Cancer-Induced Cachexia

Gullett¹,

Mazurak²,

Hebbar³

et al. 2011

Current Problems in Cancer

104

View full text Add to dashboard Cite

show abstract

“…Rayavarapu et al showed that BTZ significantly improved muscle function and reduced tumor necrosis factor α expression in the skeletal muscle of mice with myositis [12]. Furthermore, the potential use of BTZ in treating cancer cachexia has also been attempted [13]. …”

Section: Introductionmentioning

confidence: 99%

Bortezomib inhibits C2C12 growth by inducing cell cycle arrest and apoptosis

Xing

Shen

Godard

et al. 2014

Biochemical and Biophysical Research Communications

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Proteosome inhibitors such as bortezomib (BTZ) have been used to treat muscle wasting in animal models. However, direct effect of BTZ on skeletal muscle cells has not been reported. In the present study, our data showed that C2C12 cells exhibited a dose - dependent decrease in cell viability in response to increasing concentrations of BTZ. Consistent with the results of cell viability, Annexin V/PI analysis showed a significant increase in apoptosis after exposing the cells to BTZ for 24 h. The detection of cleaved caspase-3 further confirmed apoptosis. The apoptosis induced by BTZ was associated with reduced expression of p-ERK. Cell cycle analysis revealed that C2C12 cells underwent G2/M cell cycle arrest when incubated with BTZ for 24 h. Furthermore, BTZ inhibited formation of multinucleated myotubes. The inhibition of myotube formation was accompanied by decreased expression of Myogenin. Our data suggest that BTZ induces cell death and inhibits differentiation of C2C12 cells at clinically relevant doses.

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“…Proteolysis-inducing factor (PIF), a glycoprotein secreted by tumors, and substances such as glucocorticoids, angiotensin II, and TNFα can all cause muscle wasting (24). Several new agents, including androgen-receptor modulators and antagonists of inflammatory cytokines that promote muscle breakdown, are currently in clinical development for cancer cachexia treatment (6,24,25).…”

Section: Discussionmentioning

confidence: 99%

Treatment of cancer cachexia in mice by combination of dsRNA-dependent protein kinase inhibitor and medroxyprogesterone acetate

Chen

Zhang²

2011

Oncol Rep

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Abstract. Inhibitor of dsRNA-dependent protein kinase (PKRI) and medroxyprogesterone acetate (MPA) improve cancer cachexia via different mechanisms. We aimed to compare these two drugs, alone or in combination, in cancer cachexia in mice. Forty male BABL/c mice aged 6-8 weeks were randomly divided into PKRI, MPA, PKRI+MPA, placebo, and healthy control groups. The first 4 groups were injected with colon-26 adenocarcinoma and fed for 12 days and then treated with PKRI and MPA alone or in combination for 7 days. Body weight, tumor volume, wet weight of gastrocnemius muscle, serum levels of nutritional markers and cytokines were measured. The tumor growth (volume and weight) of mice treated with PKRI, MPA alone or PKRI+MPA was slower than that of placebo group. Wet weight of gastrocnemius muscle was significantly higher in PKRI and PKRI+MPA-treated than in placebo animals (P<0.01). All tumor-bearing mice had a significantly lower level of blood glucose, higher level of serum triglyceride and lower level of serum albumin compared with healthy control (P<0.001). However, PKRI, MPA and PKRI+MPA groups had a significant higher level of blood glucose and lower level of serum triglyceride compared with placebo group (P<0.001). All tumor bearing mice had a significant higher level of serum TNF-α, IL-1 and IL-6 compared with healthy control (P<0.001). Serum level of TNF-α and IL-6 was significantly lower in PKRI and PKRI+MPA-treated than in placebo animals (P<0.01). PKRI alone and combination therapy with PKRI and MPA reduce tumor growth and may alleviate cachexia.

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An update on promising agents for the treatment of cancer cachexia

Cited by 19 publications

References 26 publications

Nutritional Interventions for Cancer-Induced Cachexia

Nutritional Interventions for Cancer-Induced Cachexia

Bortezomib inhibits C2C12 growth by inducing cell cycle arrest and apoptosis

Treatment of cancer cachexia in mice by combination of dsRNA-dependent protein kinase inhibitor and medroxyprogesterone acetate

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