Antiangiogenic approach in soft-tissue sarcomas

Juan Martin-Liberal1, Ian Judson, Charlotte Benson

  • 1The Royal Marsden Hospital, Sarcoma Unit, Fulham Road, SW3 6JJ, London, UK. Juan.Martin@rmh.nhs.uk

Insights

New treatments targeting cancer blood vessel growth (neoangiogenesis) show promise for rare soft-tissue sarcomas (STS). Further research is essential to identify patient subgroups and optimize combination therapies for better outcomes.

Area of Science:

  • Oncology
  • Cancer Biology

Background:

  • Soft-tissue sarcomas (STS) are rare malignancies with limited treatment efficacy, achieving only ~20% response rates.
  • Neoangiogenesis, the formation of new blood vessels, is a critical mechanism in cancer development and progression, including in STS.

Purpose of the Study:

  • To review the current status and future directions of anti-angiogenesis strategies in soft-tissue sarcoma treatment.
  • To highlight the need for improved patient selection and combination therapies for STS.

Main Methods:

  • Review of recent Phase III clinical trial data for angiogenesis inhibitors in STS.
  • Analysis of the role of neoangiogenesis in STS pathogenesis and treatment response.

Main Results:

  • Two Phase III trials reported positive results for angiogenesis inhibitors, increasing progression-free survival in STS patients.
  • STS is unique among solid tumors for showing significant benefit from single-agent angiogenesis inhibitors.

Conclusions:

  • While promising, current anti-angiogenesis data for STS are insufficient, necessitating further investigation.
  • Identifying specific histological subtypes that benefit from angiogenesis inhibitors remains a challenge.
  • Combination studies are the current focus, as single-agent treatment is considered insufficient for optimal STS management.

Related Concept Videos

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...
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

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 hydroxylase and factor...