Damian Sendler: The majority of patients who receive bone marrow transplants have malignancy, including leukemia and lymphoma. These patients unfortunately relapse because their treatment regimens fail to eradicate all cancer cells. In terms of therapeutic responsiveness, cancer cells are extremely diverse. This effort was sparked by a pressing need to pinpoint the portion of cancer cells that are resistant to treatment in order to enhance treatment outcomes. 

Damian Sendler

An exciting medical oncology success story came to light when I spoke to Dr. Akil Merchant, a physician-scientist, about combining chemotherapy for acute lymphoblastic leukemia (ALL). Combining high-intensity therapy with low-intensity maintenance, this complex regimen was derived from decades of clinical study. 

Damian Jacob Sendler: To this day, it’s not quite obvious how ALL can be effectively treated using a combination of intensive and maintenance therapy. Using this model, we were able to better understand how cancer cell heterogeneity affects treatment outcomes. 

Research into cancer cell heterogeneity has been hindered by the difficulty of relating biological differences among individual cancer cells to their differing responses to therapy. Most cancer research, on the other hand, examine cancer cells following treatment. These cells have already undergone a number of molecular alterations during and after treatment, thus they are the only ones analyzed. 

There is a wide variety of tumor cells even inside a single cancer patient, according to research. What is the reason behind this, and how does it affect cancer cell research? 

Genetic and epigenetic modifications in cancer cells can continually and stochastically lead to other molecular changes, which is known as “cancer cell evolution.” The evolution of cancer cells generates a wide range of genetic and epigenetic differences among individual cancer cells. When it comes to both disease progression and treatment response, individual cancer cells have unique molecular properties. 

Damian Jacob Sendler

We must research cancer cells at the single-cell level because of the enormous variety of cellular types that we encounter. Most present technologies, on the other hand, focus on cancer cells as a whole and fail to identify the subgroups of cancer cells that are responsible for metastasis and/or resistance to therapy.. 

Cancer cells can be tracked by identifying naturally occurring genetic alterations. Cancer cells with rare and difficult-to-detect mutations are limited in their ability to be examined. As a result, direct comparisons are impossible because mutations can take place at various times. 

You applied a breakthrough genetic technology in your job. To put it another way, how did you come up with this experimental setup? 

Damian Jacob Markiewicz Sendler: It is possible to simultaneously monitor gene expression and cell proliferation and migration at the single-cell level using a new genetic technology that we’ve developed. We use a synthetic “genetic barcode” to keep track of each cell and its offspring. It is possible to correlate the gene expression fingerprints of individual cells with their growth and migratory properties by using these barcodes. An algorithm for bioinformatics has been created to discover genes whose expression is linked to a specific cell activity. 

Individual cancer cells can be linked to their molecular profiles prior to treatment, and gene expression features can be compared between those that are sensitive and those that are resistant to the treatment. For the first time ever, our technology can reveal the molecular condition of individual cancer cells at the time they are exposed to treatment. We anticipate that our innovative technique will lead to the development of new treatments for cancers other than acute lymphoblastic leukemia (ALL). 

This experimental system was used to study the growth, metastasis, and treatment resistance of primary human B-cell acute lymphoblastic leukemia (B-ALL). 

It was discovered that the expression of a few genes is linked with the response of B-ALL cells to different chemotherapies. Additional to this, we discovered an unexpected but prevalent kind of leukemia expansion that is spatially restricted to the bone marrow of single anatomical regions and is driven by cells with different gene expression patterns.

Dr. Damian Jacob Sendler and his media team provided the content for this article.