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Resistance to chemotherapy: new treatments and novel insights into an old problem

S Raguz1, E Yagüe

  • 1MRC Clinical Sciences Centre, Imperial College Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.

British Journal of Cancer
|July 31, 2008
PubMed

Insights

Cancer drug resistance, a major challenge, emerges early in tumorigenesis. Understanding molecular mechanisms and exploring novel therapies like cancer stem cell targeting are crucial for effective treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Cancer chemotherapy resistance is a significant clinical challenge, particularly in advanced stages.
  • Molecular mechanisms of resistance include drug inactivation, altered DNA repair, apoptosis evasion, and transporter activity.
  • Resistance also develops against targeted therapies, mirroring an evolutionary process.

Purpose of the Study:

  • To review the molecular effectors of traditional chemotherapy resistance.
  • To discuss resistance mechanisms in targeted therapies.
  • To highlight emerging concepts in cancer drug resistance, including early resistance development and novel therapeutic strategies.

Main Methods:

  • Review of existing literature on cancer drug resistance.
  • Analysis of molecular mechanisms underlying resistance to chemotherapy and targeted agents.
  • Discussion of novel technologies and concepts such as genome profiling and cancer stem cells.

Main Results:

  • Cellular models have elucidated key resistance effectors at the molecular level.
  • Resistance to targeted therapies, like imatinib, emerges similarly to traditional chemotherapy.
  • Drug resistance capability arises early in the tumorigenic process, even before full transformation.
  • Genome profiling shows potential for predicting chemotherapy outcomes.
  • The cancer stem cell paradigm offers new avenues for cell-targeted therapies.

Conclusions:

  • Understanding the molecular basis of drug resistance is essential for improving cancer treatment.
  • Early development of resistance suggests a need for proactive therapeutic strategies.
  • Novel approaches, including genome profiling and targeting cancer stem cells, hold promise for overcoming resistance.

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