Small molecule inhibitors for cutaneous T-cell lymphomas

ABSTRACT

Introduction: Cutaneous T-cell lymphomas are a group of non-Hodgkin’s T cell lymphomas showing a wide variety of clinical, histopathological and immunohistochemical findings. Cutaneous T-cell lymphomas are very difficult to treat at advanced stages and the management remains largely palliative. Therapeutic options for advanced cutaneous T-cell lymphomas have expanded in recent decades beyond traditional regimens, such as chemotherapy and radiotherapy, with molecularly targeted therapy.

Areas covered: Targeted treatment strategies using small molecule inhibitors are being extensively studied in cutaneous T-cell lymphoma. In principle, small molecule compounds can be developed to target any portion of a molecule, regardless of the target’s cellular location. In this review, we will discuss the state of the art concerning small molecule inhibitors for the treatment of advanced forms of cutaneous T-cell lymphomas.

Expert opinion: Therapeutic approaches in cutaneous T-cell lymphomas based on small molecule inhibitors have generally not achieved clinical success mainly due to the modest single agent activity, typically around 30%. This is in contrast to the results obtained in other types of cancer where small molecule compounds may be able to produce a high rate of clinical response. Consequently, the prospects for small molecule inhibitors in cutaneous T-cell lymphomas is their utilization in combination among them or with other types of therapies such as monoclonal antibodies and/or single/polychemotherapy.

KEYWORDS:

• Cutaneous T-cell lymphomas
• skin
• small molecule inhibitors
• targeted therapies

Article highlights

• Cutaneous T-cell lymphomas are a group of non-Hodgkin’s T cell lymphomas showing a wide variety of clinical, histopathological and immunohistochemical findings.

• Therapeutic options for advanced CTCLs have expanded in recent decades beyond traditional regimens, such as chemotherapy and radiotherapy, with molecularly targeted therapy.

• Therapeutic approaches in CTCLs based on small molecule inhibitors have generally not achieved clinical success mainly due to the modest single agent activity, typically around 30%.

• The future prospects for small molecule inhibitors in CTCLs is their utilization in combination among them or with other types of therapies such as monoclonal antibodies and/or single/polychemotherapy.

• Maintenance therapy with a small molecule inhibitor as single-agent after standard first line treatment could be an alternative strategy for the use of these compounds in CTCLs.

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Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

None.