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Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
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Upfront therapy for diffuse large B-cell lymphoma: looking beyond R-CHOP.

Brian T Hill1, Brad Kahl2

  • 1Department of Hematology and Medical Oncology, Taussig Cancer Institute Cleveland Clinic, Cleveland, OH, USA.

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|September 14, 2022
PubMed
Summary

Diffuse large B-cell lymphoma (DLBCL) is molecularly diverse. Precision medicine using targeted agents for specific DLBCL molecular subgroups, like with polatuzumab vedotin, is crucial for improving patient outcomes.

Keywords:
Diffuse large B-cell lymphomamolecular subtypes/clusterspolatuzumab vedotin

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Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Diffuse large B-cell lymphoma (DLBCL) is recognized as a heterogeneous disease, not a single entity.
  • Recent multiomics studies have identified at least five distinct molecular subsets within DLBCL.
  • Previous clinical trials have largely failed due to treating DLBCL as a single entity.

Purpose of the Study:

  • To review novel molecular classification systems for DLBCL.
  • To analyze phase-3 clinical trials in DLBCL, including those with negative outcomes.
  • To explore data from the POLARIX trial on polatuzumab vedotin for DLBCL treatment.

Main Methods:

  • Review of molecular classification systems.
  • Analysis of large-scale phase-3 clinical trial data.
  • Examination of specific trial data, including the POLARIX trial.

Main Results:

  • DLBCL comprises distinct molecular subgroups.
  • Novel molecular classifications offer a more refined understanding of DLBCL heterogeneity.
  • The POLARIX trial provides data supporting targeted therapies like polatuzumab vedotin.

Conclusions:

  • Future DLBCL treatment requires a precision medicine approach.
  • Targeted agents tailored to specific molecular DLBCL subgroups are essential.
  • Validated, real-time molecular assays and collaborative efforts are needed for effective precision medicine.