Version 1
: Received: 25 August 2024 / Approved: 26 August 2024 / Online: 27 August 2024 (16:43:31 CEST)
How to cite:
Anselmino, L. E.; Malizia, F.; Avila, A.; Cesatti Laluce, N.; Mamberto, M.; Zanotti, L. C.; Farré, C.; Menacho Márquez, M. Overcoming Therapy Resistance in Colorectal Cancer: Targeting Rac1 Signaling Pathway as a Potential Therapeutic Approach. Preprints2024, 2024081939. https://doi.org/10.20944/preprints202408.1939.v1
Anselmino, L. E.; Malizia, F.; Avila, A.; Cesatti Laluce, N.; Mamberto, M.; Zanotti, L. C.; Farré, C.; Menacho Márquez, M. Overcoming Therapy Resistance in Colorectal Cancer: Targeting Rac1 Signaling Pathway as a Potential Therapeutic Approach. Preprints 2024, 2024081939. https://doi.org/10.20944/preprints202408.1939.v1
Anselmino, L. E.; Malizia, F.; Avila, A.; Cesatti Laluce, N.; Mamberto, M.; Zanotti, L. C.; Farré, C.; Menacho Márquez, M. Overcoming Therapy Resistance in Colorectal Cancer: Targeting Rac1 Signaling Pathway as a Potential Therapeutic Approach. Preprints2024, 2024081939. https://doi.org/10.20944/preprints202408.1939.v1
APA Style
Anselmino, L. E., Malizia, F., Avila, A., Cesatti Laluce, N., Mamberto, M., Zanotti, L. C., Farré, C., & Menacho Márquez, M. (2024). Overcoming Therapy Resistance in Colorectal Cancer: Targeting Rac1 Signaling Pathway as a Potential Therapeutic Approach. Preprints. https://doi.org/10.20944/preprints202408.1939.v1
Chicago/Turabian Style
Anselmino, L. E., Cecilia Farré and Mauricio Menacho Márquez. 2024 "Overcoming Therapy Resistance in Colorectal Cancer: Targeting Rac1 Signaling Pathway as a Potential Therapeutic Approach" Preprints. https://doi.org/10.20944/preprints202408.1939.v1
Abstract
Colorectal cancer (CRC) is the third most commonly diagnosed type of cancer worldwide and is responsible for numerous deaths. 5-fluorouracil (5-FU) is an effective chemotherapy drug commonly used in the treatment of CRC, either as monotherapy or in combination with other drugs. However, half of CRC cases are resistant to 5-FU-based therapies. To contribute to the understanding the mechanisms underlying CRC resistance or recurrence after 5-FU-based therapies, we performed a comprehensive study integrating in silico, in vitro and in vivo approaches. We identified differentially expressed genes and enrichment of pathways associated with recurrence after 5-FU-based therapies. Using these bioinformatic data as a starting point, we selected a group of drugs that restored 5-FU sensitivity to 5-FU resistant cells. Interestingly, treatment with the novel Rac1 inhibitor, 1A-116, reversed morphological changes associated with 5-FU resistance back to a control-like status. Moreover, our in vivo studies have shown that 1A-116 affected tumor growth and the development of metastasis. All our data allowed us to postulate that targeting Rac1 represents a promising avenue for the development of new therapies for patients with CRC resistant to 5-FU-based therapies.
Keywords
colorectal cancer; resistance; small GTPases; Rac1; repositioning.
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
