Preprint / Version 1

Addressing Cold Tumors via Targeted Delivery of Radiopharmaceuticals

##article.authors##

  • Sophie Read Lexington High School

DOI:

https://doi.org/10.58445/rars.1863

Keywords:

cancer, cold tumors, radioactive payloads

Abstract

Over the course of this year, an estimated 2 million people will have been newly diagnosed with cancer. In the last two decades significant progress has been made in treating cancer however, so called “cold tumors”, remain stubbornly difficult to treat. These tumors are “invisible” to the patient’s immune system, hampering the use of immunotherapeutic strategies that have been broadly applied in the treatment of cancer.

The use of radiation in the treatment of cancer is not new. Oncologists have used radiotherapy for over 100 years. However, arming pharmaceuticals with radioactive payloads offers a new era in the precise delivery of radiation for the treatment of tumors at an individual cell level. As the mechanism of tumor cell death to radiation is independent of the immune system, radiopharmaceuticals are a promising future strategy for the treatment of “cold tumors”. This article will review the state-of-the-art of radiopharmaceuticals, their application to treatment of cold-tumors and opportunities for the future.

References

Berraondo P, Sanmamed MF, Ochoa MC, Etxeberria I, Aznar MA, et al. 2019. Cytokines in clinical cancer immunotherapy. Br. J. Cancer 120:6–15

FDA Website -

https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castr ation-resistant-prostate-cancer

Dhoundiyal S, Srivastava S, Kumar S, Singh G, Ashique S, Pal R, Mishra N, Taghizadeh-Hesary F. Radiopharmaceuticals: navigating the frontier of precision medicine and therapeutic innovation. Eur J Med Res. 2024 Jan 5;29(1):26.

Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. (2006) 313:1960–64

Galon J, Fridman WH, Pages F. The adaptive immunologic microenvironment in colorectal cancer: a novel perspective. Cancer Res. (2007) 67:1883–86

Haslam A, Prasad V. 2019. Estimation of the percentage of US patients with cancer who are eligible for and respond to checkpoint inhibitor immunotherapy drugs. JAMA Netw. Open 2:5e192535

Hofman MS, Emmett L, Sandhu S, et al. [177Lu]LuPSMA617 versus cabazitaxel in patients with metastatic castration resistant prostate cancer (TheraP): a randomised, openlabel, phase 2 trial. Lancet 2021; 397: 797–804

Kratochwil C Giesel FL, Stefanova M, Benešová M, Bronzel M, Afshar-Oromieh A, Mier W, Eder M, Kopka K and Haberkorn U. PSMA-Targeted Radionuclide Therapy of Metastatic Castration-Resistant Prostate Cancer with 177Lu-Labeled PSMA-617 Journal of Nuclear Medicine August 2016, 57 (8) 1170-1176

Miederer M. Alpha emitting nuclides in nuclear medicine theranostics. Nuklearmedizin 2022; 61: 273–79

Poty S, Francesconi LC, McDevitt MR, Morris MJ, Lewis JS. αEmitters for radiotherapy: from basic radiochemistry to clinical studies—part 1. J Nucl Med 2018a; 59: 878–84

Poty S, Francesconi LC, McDevitt MR, Morris MJ, Lewis JS. αEmitters for radiotherapy: from basic radiochemistry to clinical studies—part 2. J Nucl Med 2018b; 59: 1020–27

Sartor O, de Bono, Chi KN, et al. Lutetium 177PSMA617 for metastatic castration resistant prostate cancer. N Engl J Med 2021; 385: 1091–103

Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics. CA Cancer J Clin. 2022;72:7–33

Strosberg J, ElHaddad G, Wolin E, et al. Phase 3 trial of 177Lu dotatate for midgut neuroendocrine tumors. N Engl J Med 2017; 376: 125–35

Zabransky DJ, YarchoanM, Jaffee EM. 2023. Strategies for Heating Up Cold Tumors to Boost Immunotherapies. Ann Rev Cancer Biol Vol. 7:149-170

Downloads

Posted

2024-10-24