Article previously published in the Cutaneous Lymphoma Foundation's Forum 2018 Issue 1 newsletter.
Since the development of the “scientific method,” people have been engaged in research in efforts to answer questions, solve problems, and add to our overall knowledge. Nowhere is this more evident than in the medical field, and in the study of cutaneous lymphoma. Ongoing research efforts in cutaneous lymphoma focus on two broad areas highlighted below where significant advancements have improved treatments and outcomes of patients.
This is the broadest of the research categories. Pre-clinical/basic science data is constantly being generated by molecular biologists, cancer biologists, biochemists, pharmacologists, among others. Demonstrating how proteins and molecules interact with one another within a single cell, how cells interact with their surroundings, and how cancer cells are different from normal cells are some of the ways we can better understand disease and through that knowledge, develop potential therapeutics. It is also in this setting where we test potential new drugs outside of the human to first assess efficacy and potential side effects.
In cutaneous lymphoma there is a stream of data being published that provides new insights into its development.
For example, investigations into the role of small RNA molecules (microRNA) showed that altering microRNA levels within cells affects the growth of cutaneous lymphoma. Additionally, research on epigenetic modifiers (regulators of gene levels) has shown changes in several of these proteins. Furthermore, with the advent of high-throughput genomic sequencing, multiple scientists have used this technology to better understand the possible genetic anomalies in cutaneous lymphoma. Sequencing of the entire genome within cutaneous lymphoma has generated large amounts of data and has allowed researchers to focus their efforts on specifically altered molecular pathways. Currently, researchers are focusing on growth pathways, such as the JAK/STAT and NF-κB pathways that were discovered to be genetically altered and remain constantly active, causing cutaneous lymphoma cells to grow uncontrollably. This discovery opens up new possibilities to target these pathways therapeutically.
As compared to the pre-clinical/basic science research, human subjects/patients are involved in clinical research that also includes clinical trials.
Given the rarity of cutaneous lymphoma, clinical research for this disease is frequently comprised of case reports of a single or few patients and their treatment course and outcome or reports of a group of subjects evaluated retrospectively through use of the medical chart. Retrospective reviews have been performed on larger populations of patients and have reported on factors associated with the development of and prognosis within cutaneous lymphoma, as well as the prevalence of disease within specific areas of the world. Case reports and case series have also been useful in bringing to light the less frequently encountered subtypes of cutaneous lymphoma.
Clinical trials are the gold standard for evaluating potential new or modified (alternate dosing or combination) treatments for disease.
There are a variety of strategies that can be used within clinical trials, including the use of multiple treatment groups (some with placebo), “blinding” (either one or both the subject and investigator are unaware of which treatment group a subject is in), and “randomization” (a random assigning of subjects to treatment groups). These clinical trials are essential to start the process of critically evaluating a medication within a specific disease.
Clinical Trial Phases
- When new medications are first being evaluated in humans, Phase I clinical trials are run, which involve a small number of patients and work to develop appropriate dosing for the medication.
- Phase II clinical trials enroll a larger number of participants and their main effort is to identify the effectiveness of the treatment, and to evaluate for side effects.
- Phase III trials (sometimes run concurrently with Phase II) also address efficacy and side effect profile as well as comparing it to previously available therapy or placebo.
Through this process, the ultimate goal is to have effective and safe therapeutics approved for use through the Food and Drug Administration. Once clinical approval is gained, post-marketing evaluation continues and data is collected from patients using the medication to get a better sense of tolerability when used across the population.
There are many opportunities for clinical trials within cutaneous lymphoma. Over the last decade alone medications including histone deacetylase inhibitors, chemokine receptor antibody, and reformulated topical gel therapy have been approved for use in cutaneous T-cell lymphoma. Additionally, there are multiple ongoing clinical trials throughout the world for patients with cutaneous lymphoma, which can be found on clinicaltrials.gov.
Throughout the years we have benefited greatly from the efforts of scientists, and research continues to be a vital part of our cutaneous lymphoma community. It is through this collective work that we will continue to make strides in the fight against cutaneous lymphoma.