Related Experiment Video

Updated: May 23, 2026

Reprogramming Pancreatic Ductal Adenocarcinoma to Pluripotency
07:08

Reprogramming Pancreatic Ductal Adenocarcinoma to Pluripotency

Published on: February 2, 2024

Signalling pathways passing Src in pancreatic endocrine tumours: relevance for possible combined targeted therapies

Gabriele Capurso1, Alessia Di Florio, Claudio Sette

  • 1Digestive and Liver Disease Unit, II Medical School, University of Rome La Sapienza, Rome, Italy.

Neuroendocrinology
|March 24, 2012
PubMed

Insights

Src family kinases (SFKs) play a key role in pancreatic endocrine tumors (PETs). Inhibiting SFKs alongside mTOR inhibitors may overcome treatment resistance in PET patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Pancreatic endocrine tumors (PETs) frequently exhibit MEN1 gene mutations, PI3K/AKT/mTOR pathway deregulation, and growth factor overactivation.
  • Everolimus and sunitinib are FDA-approved for advanced PETs, but predictive markers for treatment response are lacking.
  • Cancer cells can develop resistance to targeted therapies via pro-survival feedback pathways, with limited understanding of pathway cross-talk in PETs.

Purpose of the Study:

  • To investigate the role of Src family kinases (SFKs) in pancreatic endocrine tumors (PETs).
  • To explore the novel function of SFKs in modulating mTOR pathway activity.
  • To evaluate the potential of combined SFK and mTOR inhibition as a therapeutic strategy for PETs.

Main Methods:

  • Review of existing data on molecular abnormalities in PETs.
  • Investigation of SFK's role in PET pathogenesis.
  • In vitro studies examining the effect of everolimus on PI3K/AKT signaling and the impact of simultaneous SFK inhibition.

Main Results:

  • Src family kinases (SFKs) are implicated in the development of PETs.
  • SFKs were found to modulate the activity of the mTOR pathway.
  • In vitro, everolimus treatment activated PI3K/AKT survival signaling, but co-inhibition of SFKs blocked this escape mechanism.

Conclusions:

  • SFKs play a significant role in PETs and can influence mTOR pathway activity.
  • Combined inhibition of SFKs and mTOR may represent a promising therapeutic approach to overcome treatment resistance in PETs.
  • Further investigation into combined SFK and mTOR inhibition is warranted for clinical application in PET treatment.

More Related Videos

Multianimal Magnetic Resonance Imaging for Tumor Measurements in Pancreatic Cancer Mouse Models09:18

Multianimal Magnetic Resonance Imaging for Tumor Measurements in Pancreatic Cancer Mouse Models

Published on: February 3, 2026

Syngeneic Mouse Orthotopic Allografts to Model Pancreatic Cancer06:20

Syngeneic Mouse Orthotopic Allografts to Model Pancreatic Cancer

Published on: October 4, 2022

Related Concept Videos

Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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...
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...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. 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...