Researchers have identified mammalian target of rapamycin (mTOR) as an important mediator of tumor progression. Inhibitors of mTOR signaling may be a promising way to treat a significant number of patients suffering from breast cancer. More specifically, the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mTOR pathway plays a critical role in multiple cellular functions including metabolism, proliferation, growth and survival [1]. This is a highly conserved pathway in many cancers and is linked to drug-resistance, a common side-effect with many forms of cancer therapy.
Researchers have identified mammalian target of rapamycin (mTOR) as an important mediator of tumor progression. Inhibitors of mTOR signaling may be a promising way to treat a significant number of patients suffering from breast cancer. More specifically, the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mTOR pathway plays a critical role in multiple cellular functions including metabolism, proliferation, growth and survival [1]. This is a highly conserved pathway in many cancers and is linked to drug-resistance, a common side-effect with many forms of cancer therapy. However, direct inhibition of the mTOR pathway is still a new area in breast cancer research, and it is giving clinicians the ability to modulate growth factors, as well as estrogen-dependent and estrogen-independent pathways.
According to new research published early last year, they concluded that the mTOR pathways, contribute significantly to the pathogenesis and progression of tumors." [1]
mTOR inhibitors continue being investigated as potential breakthrough cancer agents for patients with breast cancer, everolimus and rapamycin being the main representatives of this category. Data continues to pour in from clinical trials designed to evaluate the efficacy and safety of these mTOR inhibitors in all types of breast cancer.
This review of the literature highlights some of the anti-cancer reagents useful against breast cancer NOW AVAILABLE from A.G. Scientific!
Deforolimus
Catalog Number: C-2285
Method of Action: Deforolimus is a selective mTOR inhibitor; while not classified as a cancer drug, its mode of action by way of mTOR inhibition and FKBP12 binding is similar to Rapamycin (see below).
Indications/Phase of Trial: Breast Neoplasms (Phase 2); Solid Tumors (Phase 1); Advanced Cancer (Phase 1); Endometrial/Ovarian Cancer (Phase 1).
Everolimus
Catalog Number: E-2309
Method of Action: Mammalian target of rapamycin (mTOR) inhibitor
Indications/Phase of Trial: Hepatocellular carcinoma; human epidermal growth factor receptor 2-positive (HER2+) breast cancer first-line and second-line; lymphoma; nonfunctional carcinoid tumor (Phase 3; all new indications).
Approved in July in U.S., EU for advanced hormone-receptor-positive (HR+) and human epidermal growth factor Receptor 2-negative (HER2-) metastatic breast cancer with exemestane in postmenopausal women who have already received certain other medicines for their cancer.
Approved earlier for adults with pancreatic neuroendocrine tumors (PNET) that cannot be treated with surgery; adults with advanced renal cell carcinoma (RCC) when certain other medicines have not worked; adults with angiomyolipoma, seen with tuberous sclerosis complex (TSC), when surgery is not required immediately; and adults and children with TSC who have a brain tumor called subependymal giant cell astrocytoma (SEGA) that cannot be removed completely by surgery.
Iniparid
Catalog Number: I-2362
Method of Action: Poly (ADP-ribose) polymerase 1 (PARP1) inhibitor
Indications/Phase of Trial: Stage IV squamous NSCLC (Phase 3; NME); solid tumors such as sarcoma and breast, uterine, lung, and ovarian cancers (Phase 1/2).
Phase III trial in breast cancer failed January 2011 by failing to improve survival and progression-free survival (PFS) in breast cancer patients when compared with standard chemotherapy.
Lapatinib
Catalog Number: L-2371
Method of Action: Human epidermal growth factor receptor-2 (Her2) and epidermal growth factor receptor (EGFR) dual kinase inhibitor.
Indications/Phase of Trial: Metastatic Breast Cancer (Phase 2); Colorectal Cancer (Phase 2); Adjuvant Therapy (Phase 3); Gastric cancer (Phase 3); head & neck squamous cell carcinoma (Phase 3).
Rapamycin
Catalog Number: R-1018
Method of Action: Significant inhibition of mTOR and downstream targets. Studies show mTOR inhibitors create a starvation-like effect in cancer cells by interfering with cell growth, division, and metabolism, as well as, angiogenesis.
Indications/Phase of Trial: Pompe Disease (Phase 2); Arteriovenous Malformation (Stage II to IV; Phase 2); Brain Tumor, Gliiobastoma, Mixed Glioma (Phase 2); Severe Combined Immunodeficiency, Transplacental Maternal Engraftment, Stem Cell Transplant (Phase 2).
Sorafenib
Catalog Number: P-2381, P-2383
Method of Action: Dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases.
Indications/Phase of Trial: Liver cancer adjuvant (Phase 3; STORM study); kidney cancer adjuvant (Phase 3; SORCE/ASSURE study); thyroid cancer monotherapy (Phase 3; DECISION study); breast cancer with capecitabine (Phase 3; RESILIENCE study).
Approved for hepatocellular carcinoma (HCC) and RCC.
Journal References
[1] Malaguti P, Vari S, Cognetti F, Fabi A.
The Mammillian target of rapamycin inhibitors in breast cancer: current evidence and future directions. Anticancer Research. January 2013. 33 (1):21-8. <http://www.ncbi.nlm.nih.gov/pubmed/23267124>.
