CRISPR/Cas9-based manipulation of oncogenic chromosomal changes in vivo and drug impact on blood pressure

Faisal Iqbal

doi:10.53730/ijhs.v7nS1.14461

Authors

Faisal Iqbal
faisalsaleh59@ymail.com
Cancer lab, Bk Hospital, D.G. Khan, Pakistan, Department of Biological Sciences, International Islamic University, Islamabad, Pakistan

Keywords:

EML4-ALK, NSCLC, RT-PCR, CT Scan, CRISPR/Cas9

Abstract

Human malignancies develop in large part as a result of chromosomal alterations. These modifications might result in the production of gene fusions, which are aberrant combination of two distinct genes. Gene fusions are important cancer-causing factors because they can generate aberrant proteins that encourage unchecked cell proliferation and result in tumor development. Chromosome 2 inversions result in a specific gene fusion known as EML4-ALK, which is found in certain non-small cell lung cancer patients. The EML4-ALK gene fusion has clinical significance because it renders cancer cells susceptible to an exclusive class of medications known as ALK inhibitors. Targeted treatments called ALK inhibitors can selectively reduce the action of the aberrant ALK protein generated by the fusion gene. These drugs, which work by blocking ALK, can delay or stop the growth of cancer cells that have undergone the EML4-ALK fusion, providing a viable therapeutic option for individuals with this particular genetic change. The clinical significance of this gene fusion lies in its ability to render the cancer cells receptive to ALK inhibitors, enhancing their sensitivity to treatment.

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References

Thun, M. J., DeLancey, J. O., Center, M. M., Jemal, A., and Ward, E. M. (2010). The global burden of cancer: priorities for prevention. Carcinogenesis, 31 (1), 100–110.

Sun, S., Schiller, J. H., and Gazdar A. F. (2007). Lung cancer in never smokers--a different disease. Nat Rev Cancer, 7 (10), 778–790.

Eberhard, D. A., Giaccone, G., and Johnson, B.E. (2008). Biomarkers of response to epidermal growth factor receptor inhibitors in Non-Small-Cell Lung Cancer Working Group: standardization for use in the clinical trial setting. J Clin Oncol, 26 (6), 983–994.

Takeuchi, K., Choi, Y.L., Soda, M., Inamura, K., Togashi, Y., Hatano, S., Enomoto, M., Takada, S., Yamashita, Y., Satoh, Y., Okumura, S., Nakagawa, K., Ishikawa, Y., and Mano, H. (2008). Multiplex reverse transcription-PCR screening for EML4-ALK fusion transcripts. Clin Cancer Res, 14 (20), 6618–6624.

Choi, Y. L., Takeuchi, K., Soda, M., Inamura, K., Togashi, Y., Hatano, S., Enomoto, M., Hamada, T., Haruta, H., Watanabe, H., Kurashina, K., Hatanaka, H., Ueno, T., Takada, S., Yamashita, Y., Sugiyama, Y., Ishikawa, Y., and Mano, H. (2008). Identification of novel isoforms of the EML4-ALK transforming gene in non-small cell lung cancer. Cancer Res, 68 (13), 4971–4976.

Perner, S., Wagner, P. L., Demichelis, F., Mehra, R., Lafargue, C. J., Moss, B. J., Arbogast, S., Soltermann, A., Weder, W., Giordano, T. J., Beer, D. G., Rickman, D. S., Chinnaiyan, A. M., Moch, H., and Rubin, M. A. (2008). EML4-ALK fusion lung cancer: a rare acquired event. Neoplasia, 10 (3), 298–302.

Takahashi, T., Sonobe, M., Kobayashi, M., Yoshizawa, A., Menju, T., Nakayama, E., Mino, N., Iwakiri, S., Sato, K., Miyahara, R., Okubo, K., Manabe, T., and Date, H. (2010). Clinicopathologic features of non-small-cell lung cancer with EML4-ALK fusion gene. Ann Surg Oncol, 17 (3), 889–897.

Kenudson, M. M., Chirieac, L. R., Law, K., Hornick, J. L., Lindeman, N., Mark, E. J., Cohen, D. W., Johnson, B. E., Jänne, P. A., Iafrate, A. J., and Rodiget, S. J. (2010). A novel, highly sensitive antibody allows for the routine detection of ALK-rearranged lung adenocarcinomas by standard immunohistochemistry. Clin Cancer Res, 16 (5), 1561–1571.

Mandal, P. K., Ferreira, L. M., Collins, R., Meissner, T. B., Boutwell, C. L., Friesen, M., Vrbanac, V., Garrison, B. S., Stortchevoi, A., Bryder, D., Musunuru, K., Brand, H., Tager, A. M., Allen, T. M., Talkowski, M. E., Rossi, D. J., and Cowan., C. A. (2014). Efficient ablation of genes in human hematopoietic stem and effector cells using CRISPR/Cas9. Cell Stem Cell, 15(5), 643-652.

Méndez-Mancilla, A., Wessels, H. H., Legut, M., Kadina, A., Mabuchi, M., Walker, J., Robb, G. B., Holden, K., and Sanjana, N. E. (2022). Chemically modified guide RNAs enhance CRISPR-Cas13 knockdown in human cells. Cell Chem Biol, 29(2), 321-327.

Bryan, L. J., and Gordon, L. I. (2015). Releasing the Brake on the Immune System: The PD-1 Strategy for Hematologic Malignancies. Oncology, 29, 431–439.

Topalian, S. L., Hodi, F.S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., Leming, P. D., Spigel, D. R., Antonia, S. J., Horn, L., Drake, C. G., Pardoll, D. M., Chen, L., Sharfman, W. H., Anders, R. A., Taube, J. M., McMiller, T. L., Xu, H., Korman, A. J., Jure-Kunkel, M., Agrawal, S., McDonald, D., Kollia, G. D., Gupta, A., Wigginton, J. M., and Sznol, M. (2012). Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med, 366(26), 2443-54.

Poirot, L., Philip, B., Schiffer-Mannioui, C., LeClerre, D., Chion-Sotinel, I., Derniame, S., Potrel, P., Bas, C., Lemaire, L., Galetto, R., Lebuhotel, C., Eyquem, J., Cheung, G. W., Duclert, A., Gouble, A., Arnould, S., Peggs, K., Pule, M., Scharenberg, A. M., and Smith, J. (2015). Multiplex Genome-Edited T-cell Manufacturing Platform for "Off-the-Shelf" Adoptive T-cell Immunotherapies. Cancer Res, 75(18), 3853-64.

Maude, S. L., Frey, N., Shaw, P.A., Aplenc, R., Barrett, D. M., Bunin, N. J., Chew, A., Gonzalez, V. E., Zheng, Z., Lacey, S. F., Mahnke, Y. D., Melenhorst, J. J., Rheingold, S. R., Shen, A., Teachey, D. T., Levine, B. L., June, C. H., Porter, D. L., and Grupp, S. A. (2014). Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med, 371(16), 1507-17.

Kleffel, S., Posch, C., Barthel, S. R., Mueller, H., Schlapbach, C., Guenova, E., Elco, C. P., Lee, N., Juneja, V. R., Zhan, Q., Lian, C. G., Thomi, R., Hoetzenecker, W., Cozzio, A., Dummer, R., Mihm, M. C., Flaherty, K. T., Frank, M. H., Murphy, G. F., Sharpe, A. H., Kupper, T. S., and Schatton, T. (2015). Melanoma Cell-Intrinsic PD-1 Receptor Functions Promote Tumor Growth. Cell, 162(6), 1242-56.

Zhao, Z., Condomines, M., vander-Stegen, S. J. C., Perna, F., Kloss, C. C., Gunset, G., Plotkin, J., and Sadelain, M. (2015). Structural Design of Engineered Costimulation Determines Tumor Rejection Kinetics and Persistence of CAR T Cells. Cancer Cell, 28(4), 415-428.

Iqbal, F., Asif, M. S., Qureshi, A. G., Shah, J. A., Abdikaxarovich, S. A., Adil, M. N., and Hussain, A. (2023). RPA-Based colorimetric detection of SARS-Cov-2 (Covid-19) and its physiological effects. International Journal of Health Sciences, 6(S7). https://doi.org/10.53730/ijhs.v6nS7.13862

Iqbal, F., and Shabbir, M.I. (2021). Genetic analysis with pyrosequencing using loop pipetting and a light dependent resistor. Analytical Methods, 13, 5035-5047.

Naveed, A. M., Royaidar, J., Wadie, Y. R. R., GonzagaLeong-on, M. S., Iqbal, F., Hussain, A., Ali. Q., and Rasheed, A. (2022). Epidemiology and Resistance Pattern in Microbial Pneumonia: A Review: Epidemiology and Resistance Pattern in Microbial Pneumonia. Pakistan Journal of Health Sciences, 3 (05), 27-31.

Iqbal, F. (2023). Enhancing the effectiveness of Chimeric Antigen Receptor (CAR) T cells against tumors through CRISPR/Cas9-mediated PD-1 disruption. International Journal of Health Sciences, 7(S1), 1836–1850. https://doi.org/10.53730/ijhs.v7nS1.14397