Emerging therapeutic targets in diffuse large B-cell lymphoma

Murali Janakiram, Venu K. Thirukonda, Matthew Sullivan, Adam M. Petrich

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Opinion statement: The standard front-line treatment of Diffuse Large B-Cell Lymphoma (DLBCL) remains Rituximab combined with multi-agent cytotoxic chemotherapy. In spite of high response rates to this therapy, relapsed/refractory disease is observed in up to 40% of patients. It is our opinion that additional chemoimmunotherapy, followed by high-dose therapy with autologous stem cell transplant (HDT-ASCT) for responsive disease, is the optimal therapy for these patients. However, many patients cannot tolerate HDT-ASCT, or have relapsed/refractory disease in spite of it. These patients have a poor overall prognosis, and there is no clear consensus as to how these patients should be treated. Over the past decade, significant advances have been made in the understanding of the molecular genesis and subtyping of DLBCL, leading to the identification of multiple pathways and molecules that can be targeted for clinical benefit. Examples include Bcl-2, Bcl-6, cell surface markers, and myriad molecules in both the B-Cell receptor and PI3K/Akt/mTOR pathways. As agents targeting these molecules and pathways progress from preclinical models to early clinical trials, more is learned about what might predict for response to these agents, such as cell of origin classification, and/or expression of relevant molecular markers, as measured by immunohistochemistry or gene expression profiling. Both the successes and failures of these novel targeted agents promise to dramatically refine, improve, and individualize the classification and treatment of DLBCL. Therefore, it is our opinion that patients with relapsed/refractory DLBCL are an ideal population for clinical trials due to both the lack of standardized treatment, and the recent advancements in pathobiology and early-phase treatment options.

Original languageEnglish (US)
Pages (from-to)82-101
Number of pages20
JournalCurrent Treatment Options in Oncology
Volume13
Issue number1
DOIs
StatePublished - Mar 1 2012

Keywords

  • By high-dose therapy with autologous stem cell transplant (HDT-ASCT)
  • Chemoimmunotherapy
  • Diffuse Large B-Cell Lymphoma (DLBCL)
  • Multi-agent cytotoxic chemotherapy
  • Non-Hodgkin Lymphoma (NHL)
  • Rituximab
  • Therapeutic targets

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)

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