CRISPR Technology for Breast Cancer: Diagnostics, Modeling, and Therapy

Abstract

Molecularly, breast cancer represents a highly heterogenous family of neoplastic disorders, with substantial interpatient variations regarding genetic mutations, cell composition, transcriptional profiles, and treatment response. Consequently, there is an increasing demand for alternative diagnostic approaches aimed at the molecular annotation of the disease on a patient‐by‐patient basis and the design of more personalized treatments. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated (Cas) technology enables the development of such novel approaches. For instance, in diagnostics, the use of the RNA‐specific C2c2 system allows ultrasensitive nucleic acid detection and could be used to characterize the mutational repertoire and transcriptional breast cancer signatures. In disease modeling, CRISPR/Cas9 technology can be applied to selectively engineer oncogenes and tumor‐suppressor genes involved in disease pathogenesis. In treatment, CRISPR/Cas9 can be used to develop gene‐therapy, while its catalytically‐dead variant (dCas9) can be applied to reprogram the epigenetic landscape of malignant cells. As immunotherapy becomes increasingly prominent in cancer treatment, CRISPR/Cas9 can engineer the immune cells to redirect them against cancer cells and potentiate antitumor immune responses. In this review, CRISPR strategies for the advancement of breast cancer diagnostics, modeling, and treatment are highlighted, culminating in a perspective on developing a precision medicine‐based approach against breast cancer.

Methods for Stratification and Validation Cohorts: A Scoping Review

“…It is likely that in vitro diagnostics will go through an exponential increase, leading to the market authorization of new drugs that rely on them in the near future [ 71 , 72 , 73 , 74 ]. At the moment, some techniques such as CRISPR Technology [ 75 ], liquid biopsy [ 76 ] and epigenetics [ 77 ] are advancing particularly fast.…”

A narrative review of cancer molecular diagnostics: past, present, and future

“…Genetic alterations at the DNA and RNA levels are detected by using CAS12 and CAS13 in combination with the detector and Sherlock technologies. [27][28][29] CRISPR technology can be used to shear wild-type alleles to enrich the mutant allele, which, when followed by amplification and NGS, selectively improves the detection sensitivity for low-frequency mutations.…”

CRISPR-Cas9 Technology, Safety and Evaluation from an Ethical Perspective

“…Mintz ve ark., CRISPR-Cas9 sisteminin meme kanserinin tanı aşamasında, RNA-özgün tekli efektör protein C2c2 sisteminin kullanımı ile yüksek hassasiyetle nükleik asit saptamaya olanak sağlaya-bileceğini, mutasyon repertuvarını ve transkripsiyonel meme kanseri işaretlerini karakterize etmek için kullanılabileceğini bildirmişlerdir. 38 Hastalık modellemesinde, CRISPR-Cas9 teknolojisi ile hastalık patogenezinde rol oynayan onkojenlerin ve tümör baskılayıcı genlerin seçici olarak yapılandırılabileceğini, tedavi aşamasında ise hem gen terapisini geliştirmek, hem de katalitik olarak ölü varyant (dCas9) ile malign hücrelerin epigenetik manzarasını yeniden programlamak için uygulanabileceğini belirtmişlerdir. CRISPR-Cas9 ile bağışıklık hücreleri, kanser hücrelerine yönlendirilebilir ve antitümör bağışıklık tepkilerini güçlendirmek için tasarlanabilirler; kanser tedavisinde immünoterapinin önemi gün geçtikçe arttığından bu gelişmeler son derece değerlidir.…”