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Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

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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.
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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...
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Targeted Cancer Therapies02:57

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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.
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Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
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Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
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Updated: Jan 15, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
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The Bi-steric, mTORC1-Selective Inhibitor, RMC-5552, in Advanced Solid Tumors: A Phase 1 Trial.

Alison M Schram1, Abdul Rafeh Naqash2,3, Eric B Haura4

  • 1Memorial Sloan Kettering Cancer Center, New York, New York.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|October 7, 2025
PubMed
Summary
This summary is machine-generated.

RMC-5552, a novel mTORC1 inhibitor, shows promising activity and tolerability in advanced solid tumors. Tacrolimus mouthwash effectively reduced mucositis, demonstrating selective, on-mechanism antitumor effects.

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Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
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Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The PI3K/mTOR pathway is crucial in cancer development and progression.
  • RMC-5552 is a novel bi-steric inhibitor targeting mTOR complex 1 (mTORC1) selectively over mTOR complex 2 (mTORC2).

Purpose of the Study:

  • To evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of RMC-5552 in a first-in-human dose-escalation study.
  • To assess the efficacy of tacrolimus mouthwash (TM) in preventing RMC-5552-induced oral mucositis.

Main Methods:

  • A dose-escalation study of RMC-5552 (1.6-16 mg IV weekly) was conducted in 57 patients with advanced solid tumors.
  • Safety, tolerability, pharmacokinetics, and preliminary activity were assessed.
  • Tacrolimus mouthwash was tested for mucositis prophylaxis.

Main Results:

  • The most frequent adverse events included mucositis (49%), nausea (44%), and fatigue (42%).
  • Hyperglycemia incidence was low (4%), consistent with mTORC1 selectivity.
  • Tacrolimus mouthwash reduced mucositis rates from 65% to 31% between 8- and 12-mg doses.
  • Disease control rate was 64%, with one complete response in endometrial cancer.
  • Clearance of PI3K/mTOR pathway variants in circulating tumor DNA (ctDNA) was observed.

Conclusions:

  • RMC-5552 is the first bi-steric mTORC1-selective inhibitor clinically tested, showing activity at tolerable doses.
  • Selective mTORC1 inhibition with RMC-5552 overcomes hyperglycemia limitations of earlier mTOR inhibitors.
  • Tacrolimus mouthwash prophylaxis and ctDNA variant clearance support RMC-5552's selective, on-mechanism antitumor activity.