Efek Samping Temsirolimus

Gabriella Nathasya Taroreh

mammalian target of
rapamycin (mTOR)
The mammalian target of rapamycin (mTOR) is a
cytoplasmic serine/threonine protein kinase that
belongs to the phosphoinositide 3-kinase, PI3K-
related kinase family playing a key role in
regulating cell growth as well as lipid and glucose
metabolism. The protein mTOR is expressed
throughout the body and is present in brain,
cardiopulmonary system, gastrointestinal tract,
immune system, skeletal system and the
reproductive system. mTOR exists in two distinct
large multi-protein complexes: mTOR complex 1
(mTORC1) and complex 2 (mTORC2).
B. Verggravees, B. Cariou, mTOR inhibitors and diabetes, Diabetes Research and Clinical
Practice (2015)
 Temsirolimus

Recent Advances and Challenges of mTOR Inhibitors Use in the Treatment of Patients with
Tuberous Sclerosis Complex (Filipe Palavra et al, 2017)
 Recent Advances and Challenges of mTOR Inhibitors
Physicians’ Cancer Chemotherapy Drug Use in the Treatment of Patients with Tuberous
Manual (2014) Sclerosis Complex (Filipe Palavra et al, 2017)
Immunophillin-binding agent

Brody's Human Pharmacology, 6th Edition :

Mechanism-Based Therapeutics (2018),
Elsevier
Efek Samping :
Hyperglycemia
Hyperglycemia Associated With
Targeted Oncologic Treatment:
Mechanisms and Management, The
Oncologist 2016;21:1326–1336

Clinical experience with temsirolimus in the treatment of

advanced renal cell carcinoma E Zanardi, E Verzoni
et al., 2015, Vol. 7(3) 152–161
Hyperglycemia Associated With Targeted Oncologic Treatment: Mechanisms and Management,
The Oncologist 2016;21:1326–1336
Pathophysiology of hyperglycemia
induced by mTOR inhibitors
O The body regulates blood glucose levels in several ways. Excess serum glucose
increases the secretion of insulin from the pancreatic β cells. The action of insulin
begins when the hormone binds to the insulin receptor (IR) in the cell membrane. in
addition to promoting cellular uptake of glucose, IR activates intracellular pathways,
including PI3K/AKT/mTOR, affecting glucose homeostasis by increasing glycogen
synthesis and decreasing glycolysis.
(Hyperglycemia Associated With Targeted Oncologic Treatment: Mechanisms and
Management, The Oncologist 2016;21:1326–1336)

O The pathophysiology of mTOR inhibitor-related hyperglycemia involves two aspects.

First, the direct effect of mTOR inhibitors on pancreatic β-cells causes a reduction in
glucose-stimulated insulin secretion and an increase in apoptosis, with detrimental
effects on cell viability and proliferation. Second, peripheral insulin resistance has
been found to be exaggerated by mTOR inhibitors. In the liver, mTOR inhibitors
promote gluconeogenesis.
(Acute Hyperglycemia Associated with Anti-Cancer Medication , Endocrinol Metab
2017;32:23-29)

O mTOR pathways are critical components for insulin signaling. mTOR inhibition, such
as with rapamycin administration, results in reduced β-cell function and mass,
insulin resistance, decreased insulin secretion, and DM.
(Molecules to Medicine With mTOR, 2016, Elsevier)
Hyperglycemia Associated With Targeted Oncologic Treatment:
Mechanisms and Management, The Oncologist 2016;21:1326–1336
Management of Hyperglycemia

Effects of anti-cancer targeted therapies

on lipid and glucose metabolism,
European Journal of Endocrinology
(2014) 170, R43–R55
Hyperglycemia Associated With Targeted Oncologic Treatment:
Mechanisms and Management, The Oncologist 2016;21:1326–
1336
Terima Kasih 