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Targeted Cancer Therapies

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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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Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
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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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Related Experiment Video

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Primary refractory plasmablastic lymphoma: A precision oncology approach.

Hanno M Witte1,2, Anke Fähnrich3,4,5, Axel Künstner3,4,5

  • 1Department of Hematology and Oncology, University Hospital of Schleswig-Holstein, Lübeck, Germany.

Frontiers in Oncology
|March 16, 2023
PubMed
Summary

Precision oncology shows promise for primary-refractory plasmablastic lymphoma (prPBL). Molecular tumor boards (MTBs) can identify targeted therapies for this aggressive blood cancer, improving patient outcomes.

Keywords:
molecular tumor boardplasmablastic lymphomarecurrent aberrationstargeted therapywhole exome sequencingwhole transcriptome sequencing

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Area of Science:

  • Hematology
  • Oncology
  • Genomics
  • Precision Medicine

Background:

  • Hematologic malignancies are underrepresented in multidisciplinary molecular tumor boards (MTBs).
  • Primary-refractory plasmablastic lymphoma (prPBL) is a highly lethal blood cancer with a dismal clinical outcome.
  • There is an urgent medical need for personalized treatment approaches in prPBL.

Purpose of the Study:

  • To assess the potential of precision oncology in primary-refractory plasmablastic lymphoma (prPBL).
  • To evaluate the utility of a molecular tumor board (MTB) pipeline for identifying targeted therapies in prPBL.
  • To demonstrate the feasibility of molecularly stratified treatment recommendations for prPBL patients.

Main Methods:

  • Evaluation of clinicopathological and molecular-genetic data from 14 prPBL patients.
  • Application of a certified institutional MTB pipeline for data annotation and therapy recommendation.
  • Classification of genetic alterations using treatment baskets and adherence to NCT/DKTK and ESCAT criteria for evidence levels.

Main Results:

  • Comprehensive genomic/transcriptomic analysis identified molecularly stratified treatment options for all 14 prPBL cases.
  • Immunohistochemical assessment revealed targeted treatment recommendations in all cases.
  • Identified actionable targets included tyrosine kinases, PI3K-MTOR-AKT pathway, cell-cycle alterations, RAF-MEK-ERK cascade, immune evasion, and B-cell targets.

Conclusions:

  • Precision oncology demonstrates significant clinical potential in primary-refractory plasmablastic lymphoma (prPBL).
  • Molecular tumor board (MTB) inclusion at the earliest stage is crucial for prPBL patients.
  • Personalized treatment strategies are essential for improving outcomes in this aggressive hematologic malignancy.