Research with mice paves the way for injectable skin cancer treatment

February 11th 2021

Drug delivery with bioadhesive nanoparticles shows exceptional promise.

One in five people in the U.S. will develop skin cancer in their lifetime, with the most common type of malignant skin cancer, squamous cell carcinoma or SCC, killing 10,000 people each year1,2. Cases of skin cancer are steadily rising, and in fact, skin cancer is the most common cancer in the U.S. and worldwide. Skin cancer costs the U.S. economy over $8 billion annually. Effective treatments for skin cancer are crucial.

Surgical treatment is the most common first-line treatment for SCC, but SCC recurrence can be as high as 50% and surgery is suboptimal for at-risk patients. Existing nonsurgical treatments, including topical chemo- and immune-therapeutic creams or gels, fail to penetrate adequately into deeper SCCs and can also diffuse into the tumor’s blood vessels, creating the potential for systemic toxicity.

Recognizing these problems, researchers at Yale developed a solution: an injectable treatment.

How’d they do that?

A research team led by Drs. Michael Girardi and Mark Saltzman at Yale relied on a mouse model to develop this therapy. Research with mice has for many years contributed to the development of nanoparticle drug delivery, including for other diseases like HIV, tuberculosis, and breast cancer. For this study, researchers relied on approximately 40 mice. After carefully and humanely (i.e., under anesthesia) transplanting SCC cells just under the skin of the mouse’s back, the scientists then waited until the tumors grew to approximately 5mm in size. Then, researchers injected the tumors with polymer-based bioadhesive nanoparticles (BNPs) that carried the chemotherapy agent (camptothecin or CPT). To compare the efficacy of the combined BNP-CPT treatment, the researchers also treated other mice with skin tumors with CPT that was not encapsulated with the BNPs, and to control mice with skin tumors that received no drug treatment.

Laboratory mouse.

The results of this study were impressive. The BNPs bound to the tumors, remaining attached long enough to kill a significant number of the cancer cells. One single injection lasted a very long time, so the BNPs could help slowly release the chemotherapy. This, researchers say, is exactly the type of treatment that is needed to get rid of the tumor. Furthermore, the other mice with skin tumors – those treated with chemotherapy but without BNPs, and control mice – had far less retention of the chemotherapy: the CPT drug was undetectable in these mice 10 days post-injection, but for BNP-CPT mice 50% of CPT was retained. Moreover, ther BNP-CPT treatment significantly delayed tumor growth compared to the control groups for up to 70 days post-injection. Finally, the BNP-CPT mice had 20% of their tumors reach the “histologic cure” stage – no such cure was achieved in the other mice.

What’s next?

The research team is confident that this injectable treatment will rid the need for surgery in many cases of skin cancer, and may also avoid the potential of wound infections and other post-surgical complications. Ideally, patients would receive a single injection to treat their tumors, and could have multiple tumors treated in one visit. The researchers have partnered with Stradefy Biosciences Inc. to advance the preclinical development of the drug and then conduct clinical trials in human patients. Ultimately, this same type of treatment could be applied to other types of cancer as well, thereby saving lives and reducing the burdens of cancer in the U.S. and beyond. Given the fact that two people die each hour from skin cancer, the potential return on investment from this research is invaluable.

This research was recently published in the Proceedings of the National Academy of Sciences.


References:

  1. H. W. Rogers, M. A. Weinstock, S. R. Feldman, B. M. Coldiron. Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the U.S. population, 2012. JAMA Dermatol. 151, 1081–1086 (2015).
  2. S. K. T. Que, F. O. Zwald, C. D. Schmults. Cutaneous squamous cell carcinoma: Incidence, risk factors, diagnosis, and staging. J. Am. Acad. Dermatol. 78, 237–247 (2018).
  3. skincancer.org

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