“Mutant p53 proteins are typically expressed at high levels and can be antigenic,” they noted in a recent review published in Cell.6 “[F]urthermore, vaccination against mutant p53 can protect mice from cancer produced by transplanted tumors.”

Peptide vaccines and dendritic cell vaccines are now entering phase 1 and 2 clinical trial testing.6 While immunotherapy has induced p53-specific immune response in patients, it is too early to know if these will yield clinical responses, let alone survival benefits.6

Gene editing technologies like CRISPR/Cas9 might also hasten the development of TP53 mutation-targeting agents.17

Germline gene mutation editing is, however, “a ways away, with many ethical and other concerns,” noted Dr Wise.

In the end, “immunotherapy is going to be the best therapy,” according to Paul Ewald, PhD, director of the Program in Evolutionary Biology at University of Louisville in Kentucky.

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“The immune system is so much more sophisticated than any chemical we can use to target cancer,” Dr Ewald explained. “The immune system has had to deal with this [tumorigenesis] and all of the escapes for as long as humans and other organisms have been around.”

Until these therapies are better developed, awareness and risk reduction may be the best tools available.

References

  1. Asdahl PH, Ojha RP, Hasle H. Cancer screening in Li-Fraumeni syndrome. JAMA Oncol. 2017 Aug 3. doi: 10.1001/jamaoncol.2017.2459 [Epub ahead of print]
  2. Genetic testing for hereditary cancer syndromes. National Cancer Institute website. https://www.cancer.gov/about-cancer/causes-prevention/genetics/genetic-testing-fact-sheet. Accessed October 2017.
  3. Banks KC, Moline J, Marvin M, Newlin AC, Vogel KJ. 10 rare tumors that warrant a genetics referral. Fam Cancer. 2013;12(1):1-18.
  4. Evans DG. Genetic predisposition to cancer. Medicine. 2015;44(1):65-8.
  5. Sundem G. P53 “master switch” remains top target in gene signaling network controlling cancer suppression. Colorado Cancer Blogs website. http://www.coloradocancerblogs.org/p53-master-switch-remains-top-target-gene-signaling-network-controlling-cancer-suppression/. Published October 9, 2017. Accessed October 2017.
  6. Kastenhuber ER, Lowe SW. Putting p53 in context. Cell. 2017;170(6):1062-78. doi: 10.1016/j.cell.2017.08.028
  7. Mai PL, Khincha PP, Loud JT, et al. Prevalence of cancer at baseline screening in the National Cancer Institute Li-Fraumeni syndrome cohort. JAMA Oncol. 2017 Aug 3. doi: 10.1001/jamaoncol.2017.1350 [Epub ahead of print]
  8. Asdahl PH, Ojha RP, Hasle H. Cancer screening in Li-Fraumeni syndrome. JAMA Oncol. 2017 Aug 3. doi: 10.1001/jamaoncol.2017.2459 [Epub ahead of print]
  9. Churpek JE. Familial myelodysplastic syndrome/acute myeloid leukemia. Best Pract Res Clin Haematol. 2017;7:206. doi: 10.1016/j.beh.2017.10.002
  10. Baptista RL, dos Santos AC, Gutiyama LM, Solza C, Zalcberg IR. Familial myelodysplastic/acute leukemia syndromes—myeloid neoplasms with germline predisposition. Frontiers Oncol. 2017;7:206. doi: 10.3389/fonc.2017.00206
  11. Kennelly RP, Gryfe R, Winter DC. Familial colorectal cancer: patient assessment, surveillance and surgical management. Eur J Cancer Surg. 2017;43:294-302.
  12. Oliveira C, Pinheiro H, Figueiredo J, Servca R, Carneiro F. Familial gastric cancer: genetic susceptibility, pathology, and implications for management. Lancet Oncol. 2015;16:e50-70.
  13. Durno C, Boland CR, Cohen S, et al. Recommendations on surveillance and management of biallelic mismatch repair deficiency (BMMRD) syndrome: a consensus statement by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterol. 2017;152:1605-14. doi: 10.1053/j.gastro.2017.02.011
  14. Ramamurthy C, Chertock Y, Hall MJ. Randomized controlled trials in hereditary cancer syndromes. Surg Oncol Clin N Am. 2017;26:729-50. doi: 10.1016/j.soc.2017.05.011
  15. Lambertini M, Goldrat O, Toss A, et al. Fertility and pregnancy issues in BRCA-mutated breast cancer patients. Cancer Treat Rev. 2017;59:61-70. doi: 10.1016/j.ctrv.2017.07.001
  16. Westdorp H, Kolders S, Hoogerbrugge N, de Vries IJ, Jongmans MC, Schreibelt G. Immunotherapy holds the key to cancer treatment and prevention in constitutional mismatch repair deficiency (CMMRD) syndrome. Cancer Lett. 2017;403:159-64. doi: 10.1016/j.canlet.2017.06.018
  17. Zhou R, Xu A, Gingold J, Strong LC, Zhao R, Lee DF. Li-Fraumeni Syndrome disease model: a platform to develop precision cancer therapy targeting oncogenic p53. Trends Pharmacol Sci. 2017;38(10):908-27.