Addressing Resistance to Targeted Therapies in Metastatic Colorectal Cancer

Oncology (Williston Park). 2021 Oct 21;35(10):654-660. doi: 10.46883/ONC.2021.3510.0654.

Abstract

Metastatic colorectal cancer (mCRC) is the second most common cause of cancer-related death worldwide. In the mid-1980s, the median overall survival (OS) for patients with mCRC ranged from 10 to 12 months from the time of initial diagnosis. In more recent studies, this median has more than doubled and is commonly reported at more than 25 to 30 months. These improvements are due, in large part, to the introduction of multiple novel agents during the last 3 decades. Despite these improvements, however, nearly all patients treated with palliative chemotherapy will eventually develop resistance and ultimately succumb to progression of metastatic disease. Understanding the mechanisms by which malignant cells evade treatment could unlock novel therapeutic strategies that overcome resistance and improve survival. In this review, we will discuss some of the drivers of therapeutic resistance in patients with mCRC and present some novel strategies to overcome resistance.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Cell-Free Nucleic Acids / metabolism
  • Circulating Tumor DNA / metabolism*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology*
  • Drug Resistance, Neoplasm / genetics
  • Drug Resistance, Neoplasm / physiology*
  • ErbB Receptors / antagonists & inhibitors
  • Humans
  • Molecular Targeted Therapy
  • Neoplasm Metastasis
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Receptor, ErbB-2 / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • Cell-Free Nucleic Acids
  • Circulating Tumor DNA
  • KRAS protein, human
  • ERBB2 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)