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Related Concept Videos

Cancer Therapies02:49

Cancer Therapies

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Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
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Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
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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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Hypoxia01:23

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Hypoxia is a medical condition characterized by an inadequate oxygen supply to body tissues. It typically manifests as a bluish discoloration of the skin and mucosae, especially in fair-skinned individuals, when hemoglobin (Hb) saturation drops below 75%.
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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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Targeting hypoxia in solid and haematological malignancies.

Bill Harris1, Sana Saleem2, Natalie Cook1,3

  • 1Experimental Cancer Medicine Team, Christie NHS Foundation Trust, Manchester, UK.

Journal of Experimental & Clinical Cancer Research : CR
|November 2, 2022
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Tumour hypoxia, a lack of oxygen in cancers, drives aggressive disease and treatment resistance. Targeting hypoxia therapeutically shows promise but faces clinical challenges, necessitating further research in human models.

Keywords:
CancerHaematologicalHypoxiaSolid tumours

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Area of Science:

  • Oncology
  • Cancer Biology
  • Translational Medicine

Background:

  • Tumour hypoxia is prevalent in solid and haematological malignancies, arising from oxygen demand exceeding supply.
  • Hypoxia correlates with treatment resistance, aggressive disease, metastasis, and poorer patient prognosis.
  • Key downstream factors like Hypoxia Inducible Factor 1 (HIF1) mediate hypoxia's effects on angiogenesis, immune evasion, and metabolism.

Purpose of the Study:

  • To review current methods for targeting tumour hypoxia.
  • To discuss assessments for planning future clinical trials.
  • To outline key clinical trials and their limitations in solid and haematological cancers.

Main Methods:

  • Review of existing literature on tumour hypoxia.
  • Analysis of therapeutic strategies targeting hypoxia and its downstream effectors.
  • Examination of clinical trial data and outcomes.

Main Results:

  • Hypoxia influences multiple cancer hallmarks, including angiogenesis, immune response, and metastasis.
  • Therapeutic strategies include hypoxia-activated prodrugs (HAPs) and inhibitors of HIF1, mTOR, and VEGF.
  • Clinical trials have faced challenges despite promising preclinical data.

Conclusions:

  • Targeting tumour hypoxia is a promising therapeutic avenue but requires further research.
  • Understanding hypoxia's molecular mechanisms in human models is crucial for future trial design.
  • Optimizing hypoxia-targeting strategies may improve outcomes in cancer patients.