Genetics in the News Report

The article “Targeting DDR2 Enhances Tumor Response to Anti–PD-1 Immunotherapy” by Tu et al. (2019) aimed at using a functional genomics-based method to identify drug target genes. The focus is to identify the genes that can also be targeted alongside anti-PD-l to promote tumor clearance and an increase in immune response. The researchers provide a rationale for their approach by claiming that across many cancer types, targeting antibodies is an effective treatment intervention. Most patients who receive such therapy demonstrate positive responses, however, there is a subset of patients whose cancer condition continues to deteriorate. As such, this highlights the need for other approaches that induce immune responsiveness to cancerous tumors.

The article is significant because it highlights a weighty matter that is of great interest to the cancer society. The issue of combining therapies is the foundation under which the scholar undertake the research. They identify the great need to combine different cancer therapies as demonstrated by the numerous clinical studies. Cancer treatment has been revolutionized by the development of immunotherapy (Zahavi and Weiner 158). The concept of immunotherapy has revolutionized the clinical approach towards cancer treatment. Promising results from such interventions have been observed, and there is hope in further research. The combination of PD-1 with other forms of treatment in a bid to improve response to drugs is vigorously researched. From the extensive studies on treatment modalities, the researchers identified that the number of studies is too high and eligible cancer patients to be used in the studies may be insufficient. Subsequently, this translates to researchers conducting low powered research designs as such; the outcomes will be controversial as some may not consider them reliable. So the authors of the article realized that these issues necessitate the design of a therapeutic combination approach that applies rationale in deciding the treatment combinations.

The research seeks to detect genes whose inhibition increases the likelihood of a response to anti-PD-1 immunotherapy. A new mechanism is defined by the study where DDR2 collagen receptor targeting causes a considerably heightened response. The researchers demonstrate that the combination is widespread across numerous tumor prototypes which signify various types of cancer.  Fibrillar collagen activates DDR2 which is a protein receptor, it, therefore, plays a crucial role in monitoring the interaction within the collagen cell (Tu et al. 5). Modification to the DDR2 including mutations, overexpression, and amplification is documented as occurring across many types of cancer cells. Furthermore, these alterations are known to cause more aggressive types of cancer. For the study, dasatinib drug was selected for use as a potential DDR2 inhibitor. Additionally, the drug is extensively used in clinical trials for tumors, and it is also a drug that targets DDR2 which the gene of interest.

In comparison to genome-wide screens which primarily focus on developing an advanced understanding of the process of immunotherapy resistance, the in vivo screening approach employed in the study provides a more direct guideline for applying knowledge from studies. The results produced by the research provided a strong justification for conducting further studies that investigate how immune evasion is supported by increased collagen and DDR2. The study identifies that an interesting point in conducting studies is determining if the strategy to target collagen signaling is viable. A common aspect of a majority of tumor types is collagen signaling, so it is a factor of interest to evaluate.


Works Cited

Tu, Megan M. et al. “Targeting DDR2 Enhances Tumor Response To Anti–PD-1 Immunotherapy”. Science Advances, vol 5, no. 2, 2019, p. eaav2437. American Association For The Advancement Of Science (AAAS), doi:10.1126/sciadv.aav2437. Accessed 8 Mar 2019.

Zahavi, David, and Louis Weiner. “Targeting Multiple Receptors To Increase Checkpoint Blockade Efficacy.” International Journal Of Molecular Sciences, vol 20, no. 1, 2019, p. 158. MDPI AG, doi:10.3390/ijms20010158. Accessed 8 Mar 2019.