Targeted Therapy In Hematologic Malignancies
HEMATOPATHOLOGY: GENOMIC MECHANISMS OF NEOPLASTIC DISEASES(2010)
摘要
The utility of tumor-specific molecular genetic signatures in the clinical care of patients with cancer has been well documented.
Many diagnostic criteria of disease categories and subtypes have been revised to include defining genetic signatures such
as the BCR–ABL1 fusion protein produced as a result of the formation of the Philadelphia chromosome, a translocation between
chromosomes 9 and 22. This is the hallmark diagnostic finding in more than 95% of patients with chronic myelogenous leukemia
(CML). Genetic markers have also been recognized as prognostic indicators of likelihood of response to treatment or disease
progression. BCR–ABL1 is an indicator of poor prognosis in some pediatric patients with ALL because this marker is associated with poor response
to therapy and a poor duration of response. Studies from many clinical centers have also validated the utility of using these
signatures to stratify patients to the most effective treatment regimens based on historic outcome-based studies. These therapies
have ranged from chemotherapy and stem cell transplantation to immunotherapy and small molecule drugs. In addition, the defining
molecular signature may be used to track the efficacy of the treatment by monitoring levels of residual cancer cells throughout
the course of treatment. Now anti-cancer therapies may specifically target the tumor-specific gene products within the cancer
cells, bypassing normal cells of the same lineage. Only cancers that bear the genetic mutations will respond to these targeted
therapies, requiring specific, sensitive, and timely molecular diagnostic tools to aid the oncologist in characterizing the
cancers of patients who may be candidates for these genetically designed drugs. In this chapter we will review the categories
of targeted therapies that are in use to treat hematologic malignancies including leukemia, lymphoma, and multiple myeloma.
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关键词
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