Related Experiment Video

Updated: May 7, 2026

A 3D Organotypic Melanoma Spheroid Skin Model
08:49

A 3D Organotypic Melanoma Spheroid Skin Model

Published on: May 18, 2018

Navigating the therapeutic complexity of PI3K pathway inhibition in melanoma

Lawrence N Kwong1, Michael A Davies

  • 1Authors' Affiliations: Departments of Genomic Medicine, Melanoma Medical Oncology, and Systems Biology, University of Texas MD Anderson Cancer Center, Houston, Texas.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|October 4, 2013
PubMed

Insights

Targeting the phosphoinositide 3-kinase (PI3K)-AKT pathway offers a promising strategy for melanoma treatment. Overcoming resistance mechanisms is key to realizing clinical benefits from these novel combinatorial approaches.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Melanoma treatment is advancing with combinatorial therapies, building on single-agent successes.
  • The phosphoinositide 3-kinase (PI3K)-AKT pathway is a key target due to its role in melanoma pathogenesis and resistance.
  • Aberrations activating the PI3K-AKT pathway are found in melanoma, driving the need for targeted therapies.

Purpose of the Study:

  • To review the current understanding of the PI3K-AKT pathway in melanoma.
  • To discuss emerging strategies for targeting this pathway in melanoma treatment.
  • To highlight challenges and opportunities in developing PI3K-AKT targeted therapies for melanoma.

Main Methods:

  • Literature review of current research on the PI3K-AKT pathway in melanoma.
  • Analysis of molecular pathogenesis, heterogeneity, and resistance mechanisms.
  • Evaluation of preclinical models and available targeting compounds.

Main Results:

  • The PI3K-AKT pathway is frequently activated in melanoma, presenting a strong rationale for therapeutic targeting.
  • Preclinical models and targeted compounds are available for investigating PI3K-AKT inhibition.
  • Key challenges include patient selection, feedback loops, and pathway cross-talk mediating resistance.

Conclusions:

  • Targeting the PI3K-AKT pathway represents a significant clinical opportunity in melanoma.
  • Effective strategies require addressing resistance mechanisms like feedback loops and cross-talk.
  • Further research is needed to optimize patient selection and maximize clinical benefit.

Related Concept Videos

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...
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...
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...
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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...