New Cancer Drug May Not Work As Intended

A near-miraculous cancer treatment drug has had a great impact on patients with advanced cancer. The drug works by activating PD-1, a protein on the surface, and blocks tumor protein PD-L1 from suppressing T cells.

Anti-PD-1 Drug

Anti-PD-1 Drug

A 65-year-old endometrial cancer patient who was still healthy and mobile was put under treatment with this drug. Three weeks into treatment, her liver, and abdominal tumors were not responding as expected. Instead, they had significantly grown into the size of an orange. Although she was not going to survive cancer per the initial oncologist report, this drug had brought her closer to death.

After gathering papers, narrative reports, and analysis findings of such tumors, there is uncertainty. Some analysts wonder whether the tumors would have grown regardless of whether the patients were to be exposed to the checkpoint inhibitor treatment. Having specialists torn into two, researchers are trying to find out if the rapid tumor progression is real. If so, they will work towards identifying markers that will separate those who should receive these drugs and the ones to avoid.

Hyper progression cases

The first hyper progression concerns arose in 2016 when 12 out of 131 patients’ tumors had a double growth rate in a span of 3 months into anti-PD-1 treatment. Since then there have been about six groups of reported checkpoint inhibitor cases of triggered hyper-progression with 7% in various cancers and about 20% for neck and head tumors.

Hyper-progression remains a mystery as nobody has proven the relationship between the tumor rapid reaction and the anti-PD-1 drugs. It is cautioned that the spur might be the natural course of the disease, noting that at one point in cancer treatment things tend to go south fast. Additionally, there is no definite way to measure a standard rate of growth as every individual case is different. Without a standard measure, it becomes hard to get a point of reference or grounds to base hyper-progression claims.

Studies to establish the cause

A current study using mouse models and cancer cell lines is underway. This was after a clue was found in patients with hyper-progressive tumors. Most patients had mutations in cancer genes EGFR, MDM2, or MDM4. In the study, these genes undergo alterations in an attempt to find the connection to growth accelerating molecules.

In another study, immune cells known as macrophages found around tumors are suspected to suppress anticancer responses. It was observed that tumors developed fast in mice subjected to the anti-PD-1 drug compared to those that did not.

However, none of these studies have conclusively established the primary cause of tumor hyper-progression and its relationship to the anti-PD-1 drug such as Cemiplimab, Pembrolizumab, and Nivolumab. Researchers are still looking for baseline biological and clinical variables to identify which patients are best suited for the anti-PD-1 treatment.

If specialists can identify the genetic traits and other biomarkers that indicate individual reactions, patients can be able to either access or avoid PD-1 inhibitors from the onset of their cancer treatment. Establishing the cause of hyper-progression would be a medical milestone in the cancer field. It would be easy to map a treatment plan once the risks are identified at the initial biopsy.


New drugs that unleash the immune system on cancers may backfire, fueling tumor growth

Schlom, Jeffrey, and James L. Gulley. “Vaccines as an Integral Component of Cancer Immunotherapy.” JAMA, vol. 320, no. 21, 2018, pp. 2195–2196.

Kaiser, J. (2019). New drugs that unleash the immune system on cancers may backfire, fueling tumor growth. Science. doi: 10.1126/science.aax5021

Gunda, Viswanath, et al. “Combinations of BRAF Inhibitor and Anti-PD-1/PD-L1 Antibody Improve Survival and Tumour Immunity in an Immunocompetent Model of Orthotopic Murine Anaplastic Thyroid Cancer.” British Journal of Cancer, vol. 119, no. 10, 2018, pp. 1223–1232.

Sato, Hiro, et al. “DNA Double-Strand Break Repair Pathway Regulates PD-L1 Expression in Cancer Cells.” Nature Communications, vol. 8, no. 1, 2017, pp. 1751–1751.



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