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Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...

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Targeting mTOR pathways in human malignancies.

Angelica Fasolo1, Cristiana Sessa

  • 1Unit of New Drugs & Innovative Therapies, Department of Medical Oncology Fondazione Centro San Raffaele del Monte Tabor, Via Olgettina n° 60, 20132, Milano, Italy. fasolo.angelica@hsr.it

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The mammalian target of rapamycin (mTOR) pathway is crucial in cancer. First-generation mTOR inhibitors like temsirolimus and everolimus show efficacy, while newer inhibitors demonstrate promising preclinical anti-cancer activity.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The mammalian target of rapamycin (mTOR) pathway is a key regulator of cell growth, survival, and angiogenesis.
  • Dysregulation of the PI3K/AKT/mTOR pathway is common in human cancers, making it a significant therapeutic target.

Purpose of the Study:

  • To review current data on the mTOR pathway and its inhibitors in cancer treatment.
  • To summarize preclinical and clinical findings for first-generation mTOR inhibitors (temsirolimus, everolimus, deferolimus).
  • To discuss the rationale and data for second-generation mTOR inhibitors.

Main Methods:

  • Comprehensive literature review of published studies on the mTOR pathway.
  • Analysis of data on rapalogs and novel mTOR inhibitors in cancer research.

Main Results:

  • Temsirolimus and everolimus are approved for metastatic renal cell carcinoma (RCC) and other cancers.
  • Newer mTOR inhibitors exhibit potent in vitro and in vivo antiproliferative activity.
  • Preclinical studies show favorable safety profiles and tumor regression with novel mTOR inhibitors.

Conclusions:

  • First-generation mTOR inhibitors have established roles in treating specific cancers.
  • Second-generation mTOR inhibitors show significant promise as single agents or in combination therapies.
  • Further clinical evaluation of novel mTOR inhibitors is warranted for broad anti-cancer applications.