Scope
Several complexities dictate the tumor cell response to stress. Cellular Senescence arises a primary phenotype that influences the fate of tumor cells following stress precipitated by the exposure to anticancer therapy, which is often termed “Therapy-Induced Senescence” (TIS). TIS is now being recognized as a major contributor to cancer therapy outcomes, a fundamental element of the tumor microenvironment, and a primary target for novel anticancer therapeutics. In addition to contributing to treatment resistance, facilitation of migratory and immune-evasive potential, and tumor dormancy, TIS accounts for the development of several therapy-induced adverse effects.
The Saleh lab studies the roles, mechanisms and significance of TIS in cancer treatment. We use preclinical and clinical models to understand the exact role of TIS in mediating the ultimate tumor cell date. We also focus on investigating the use of pharmacological interventions to modulate the effects mediated by the development of TIS as a consequence to anticancer therapy. The lab also focuses on studying the contribution of TIS to multiple toxicities that result from cancer treatment.
Members
Our team is comprised of experienced researchers and scientists with a diverse range of specializations. We have expertise in cancer pharmacology, cellular senescence, drug discovery, and preclinical and clinical development. Our team members have received their training from top institutions around the world and are dedicated to advancing the field of biomedical research.
Tareq Saleh MD, PhD
Principal Investigator
Associate Professor of Pharmacology and Toxicology
Arabian Gulf University
The Hashemite University
tareq@hu.edu.jo
tareqnrs@agu.edu.bh
Tel: +973 17 239 547
Sofian Al Shboul MD, PhD
Assistant Professor of Molecular and Clinical Medicine
The Hashemite University
sofian@hu.edu.jo
Tel: +962 (05) 390 3333 (5608)
Ashraf I. Khasawneh MD, PhD
Associate Professor of Virology
Clinical Microbiology Fellow
The Hashemite University
National Institutes of Health
ashrafkh@hu.edu.jo
ashraf.khasawneh@nih.gov
Tel: +962 (05) 390 3333 (5562)
Ola Abu Al Karsaneh, MD
Assistant Professor of Pathology
The Hashemite University
olaa@hu.edu.jo
Ahmad Alhesa, MSc
Research Associate
ahm8171602@ju.edu.jo
Mohammed El-Sadoni, MSc
Research Associate
mhm8191130@ju.edu.jo
Nebras Melhem, MSc
Research Associate
nebras@hu.edu.jo
Kholoud Friehat
Master Student
k.frehat@ju.edu.jo
Ongoing Projects
1. Investigating the Role of Therapy-induced Senescence (TIS) in Cancer Biology and Treatment Outcomes
· Elucidating how standard and targeted anticancer therapies trigger TIS in tumor cells and how this modulates tumor regression, tumor dormancy, recurrence, and long-term prognosis.
· Defining the contribution of TIS to clinical therapeutic responses and resistance.
· Dissecting the mechanistic connection between TIS and autophagy in tumor survival and persistence.
· Understanding the Interplay Between Senescence, Stemness, and the Tumor Immune Microenvironment
2. Exploring the Therapeutic Potential of Senotherapeutics in Cancer Treatment
· Characterizing senolytic and senomorphic agents as targeted strategies to selectively eliminate or modulate senescent tumor cells.
· Investigating mechanisms of action, therapeutic selectivity, and pathways of senolytic resistance.
3. Targeting Therapy-Induced Senescence (TIS) to Mitigate Chemotherapy-Associated Toxicities
· Understanding the role of off-target senescence in mediating key dose-limiting adverse effects, including:
§ Chemotherapy-induced cognitive impairment (“chemobrain”)
§ Chemotherapy-induced peripheral neuropathy (CIPN)
§ Chemotherapy-related nephrotoxicity
4. Senescence and Cancer Initiation: Oncogene-induced Senescence (OIS) and Early Tumorigenesis
· Molecular identification and characterization of OIS in precancerous lesions.
· Assessing viral infection–induced senescence (e.g., HPV) as a carcinogenic driver and potential preventive therapeutic target.
5. Investigating Senescence-Associated Mechanisms in Cell-Based and Extracellular Vesicle Therapies
Selected Publications
Melhem N, Qutifan S, Alsalem M, Saleh T. Potential Connections Between Senescence and Chemobrain: An Early Overview of Literature. Ageing Research Reviews. 2025 Sep 10:102896. doi: 10.1016/j.arr.2025.102896
Almudimeegh S, Almutairi MM, Softah A, Alhazzani K, Binobaid L, Alshammari M, Sobeai HMA, Saleh T, Alotaibi MR, Alhoshani A. Talazoparib and radiation enhance the senolytic efficacy of venetoclax in therapy-induced senescent triple-negative breast cancer cells. Saudi Pharm J. 2025 Aug 26. doi: 10.1007/s44446-025-00034-2.
Al Shboul S, Awad H, Abu-Humaidan A, Ababneh NA, Khasawneh AI, Saleh T. Oncogene-Induced Senescence Transcriptomes Signify Premalignant Colorectal Adenomas. Current Issues in Molecular Biology. 2025 Mar 25;47(4):221.https://doi.org/10.3390/cimb47040221
Saleh T, Greenberg EF, Faber AC, Harada H, Gewirtz DA. A Critical Appraisal of the Utility of Targeting Therapy-induced Senescence for Cancer Treatment. Cancer Research. 2025 Mar 4. https://doi.org/10.1158/0008-5472.CAN-24-2219
Khasawneh AI, Al Shboul S, Himsawi N, Al Rousan A, Shahin NA, El-Sadoni M, Alhesa A, Abu Ghalioun A, Khawaldeh S, Shawish B, Mahfouz SA. Resolution of oncogene-induced senescence markers in HPV-infected cervical cancer tissue. BMC cancer. 2025 Jan 21;25(1):111. https://doi.org/10.1186/s12885-025-13499-0
Saleh T, Himsawi N, Al Rousan A, Alhesa A, El-Sadoni M, Khawaldeh S, Shahin NA, Ghalioun AA, Shawish B, Friehat K, Alotaibi MR. Variable Expression of Oncogene-Induced Senescence/SASP Surrogates in HPV-Associated Precancerous Cervical Tissue. Current Issues in Molecular Biology. 2024 Dec 2;46(12):13696-712. doi.org/10.3390/cimb46120818
Saleh T. Therapy-induced senescence is finally escapable, what is next? Cell Cycle. 2024 Jun 16:1-9. doi: 10.1080/15384101.2024.2364579
Elshazly AM, Shahin U, Al Shboul S, Gewirtz DA, Saleh T. A conversation with ChatGPT on contentious issues in senescence and cancer research. Mol Pharmacol. 2024 Mar 8:MOLPHARM-EMC-2024-000871. doi: 10.1124/molpharm.124.000871
Saleh, T., Naffa, R., Barakat, N.A. et al. Cisplatin Provokes Peripheral Nociception and Neuronal Features of Therapy-Induced Senescence and Calcium Dysregulation in Rats. Neurotox Res. 2024. doi.org/10.1007/s12640-024-00690-7
Abu‐Humaidan AH, Ismail MA, Ahmad FM, Al Shboul S, Barham R, Tadros JS, Alhesa A, El‐Sadoni M, Alotaibi MR, Ababneh NA, Saleh T. Therapy‐induced senescent cancer cells exhibit complement activation and increased complement regulatory protein expression. Immunology and Cell Biology. 2024. doi: 10.1111/imcb.12727
Alsalem M, Ellaithy A, Bloukh S, Haddad M, Saleh T. Targeting therapy-induced senescence as a novel strategy to combat chemotherapy-induced peripheral neuropathy. Support Care Cancer. 2024 Jan 5;32(1):85. doi: 10.1007/s00520-023-08287-0
Al Shboul S, Boyle S, Singh A, Saleh T, Alrjoub M, Abu Al Karsaneh O, Mryyian A, Dawoud R, Gul S, Abu Baker S, Ball K, Hupp T, Brennan PM. FISH analysis reveals CDKN2A and IFNA14 co-deletion is heterogeneous and is a prominent feature of glioblastoma. Brain Tumor Pathol. 2023 Dec 14. doi: 10.1007/s10014-023-00473-6
Softah A, Alotaibi MR, Alhoshani AR, Saleh T, Alhazzani K, Almutairi MM, AlRowis R, Alshehri S, Albekairy NA, Harada H, Boyd R. The Combination of Radiation with PARP Inhibition Enhances Senescence and Sensitivity to the Senolytic, Navitoclax, in Triple Negative Breast Tumor Cells. Biomedicines. 2023 Nov;11(11):3066. doi.org/10.3390/biomedicines11113066
Saleh T, Bloukh S, Hasan M, Al Shboul S. Therapy-induced senescence as a component of tumor biology: Evidence from clinical cancer. Biochim Biophys Acta-Reviews Canceri. 2023;1878:188994. doi:10.1016/J.BBCAN.2023.188994
Al Shboul S, El-Sadoni M, Alhesa A, et al. NOXA expression is downregulated in human breast cancer undergoing incomplete pathological response and senescence after neoadjuvant chemotherapy. Sci Rep. 2023;13:15903. doi:10.1038/s41598-023-42994-2
El-Sadoni M, Shboul S Al, Alhesa A, et al. A three-marker signature identifies senescence in human breast cancer exposed to neoadjuvant chemotherapy. Cancer Chemother Pharmacol. 2023;91(4):345-360. doi:10.1007/S00280-023-04523-W
DeLuca VJ, Saleh T. Insights into the role of senescence in tumor dormancy: mechanisms and applications. Cancer Metastasis Rev. 2023;42(1):19-35. doi:10.1007/S10555-023-10082-6
Shboul S Al, DeLuca VJ, Dweiri Y Al, Saleh T. Can 3D bioprinting solve the mystery of senescence in cancer therapy? Ageing Res Rev. 2022;81:101732. doi:10.1016/j.arr.2022.101732
Alotaibi M, Al-Aqil F, Alqahtani F, et al. Alleviation of cisplatin-induced neuropathic pain, neuronal apoptosis, and systemic inflammation in mice by rapamycin. Front Aging Neurosci. 2022;14. doi:10.3389/FNAGI.2022.891593
Saleh T, Gewirtz DA. Considering therapy-induced senescence as a mechanism of tumour dormancy contributing to disease recurrence. Br J Cancer. 2022;126(10):1363-1365. doi:10.1038/S41416-022-01787-6
Carpenter V, Saleh T, Min Lee S, et al. Androgen-deprivation induced senescence in prostate cancer cells is permissive for the development of castration-resistance but susceptible to senolytic therapy. Biochem Pharmacol. 2021;193:114765. doi:10.1016/J.BCP.2021.114765
Saleh T, Carpenter VJ. Potential Use of Senolytics for Pharmacological Targeting of Precancerous Lesions. Mol Pharmacol. September 2021:MOLPHARM-EMC-2021-000361. doi:10.1124/MOLPHARM.121.000361
Saleh T, Alhesa A, Al-Balas M, et al. Expression of therapy-induced senescence markers in breast cancer samples upon incomplete response to neoadjuvant chemotherapy. Biosci Rep. 2021;41(5):BSR20210079. doi:10.1042/bsr20210079
Saleh T, Carpenter VJ, Bloukh S, Gewirtz DA. Targeting tumor cell senescence and polyploidy as potential therapeutic strategies. Semin Cancer Biol. 2022;81:37-47. doi:10.1016/J.SEMCANCER.2020.12.010
Carpenter VJ, Patel BB, Autorino R, Smith SC, Gewirtz DA, Saleh T. Senescence and castration resistance in prostate cancer: A review of experimental evidence and clinical implications. Biochim Biophys acta Rev cancer. 2020;1874(2):188424. doi:10.1016/J.BBCAN.2020.188424
Saleh T, Carpenter V, Tyutyunyk‐Massey L, et al. Clearance of therapy‐induced senescent tumor cells by the senolytic ABT‐263 via interference with BCL‐X L ‐BAX Interaction. Mol Oncol. 2020;14(10):1-16. doi:10.1002/1878-0261.12761
Saleh T, Bloukh S, Carpenter VJ, et al. Therapy-Induced Senescence: An “Old” Friend Becomes the Enemy. Cancers (Basel). 2020;12(4):822. doi:10.3390/cancers12040822
Saleh T, Tyutyunyk-Massey L, Gewirtz DADA. Tumor Cell Escape from Therapy-Induced Senescence as a Model of Disease Recurrence after Dormancy. Cancer Res. 2019;79(6):1044-1046. doi:10.1158/0008-5472.CAN-18-3437
Saleh T, Tyutyunyk-Massey L, Murray GFGF, et al. Tumor cell escape from therapy-induced senescence. Biochem Pharmacol. 2019;162:202-212. doi:10.1016/j.bcp.2018.12.013
Carpenter VJ, Saleh T, Gewirtz DA. Senolytics for cancer therapy: Is all that glitters really gold? Cancers (Basel). 2021;13(4):723. doi:10.3390/cancers13040723
Alotaibi M, Sharma K, Saleh T, Povirk LFLFLF, Hendrickson EAEAEA, Gewirtz DADA. Radiosensitization by PARP Inhibition in DNA Repair Proficient and Deficient Tumor Cells : Proliferative Recovery in Senescent Cells. Radiat Res. 2016;185(3):229-245. doi:10.1667/RR14202.1
Meetings
Our Collaborators
David A. Gewirtz
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Virginia, USA.
Nidaa Ababneh
Cell Therapy Center, The University of Jordan, Amman, 11942, Jordan
Mohammad Alsalem
Department of Anatomy and Histology, The University of Jordan, Amman, Jordan.
Ted Hupp
Cancer Research UK Edinburgh Centre, MRC Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, Scotland.
Heyam Awad
Department of Pathology, Microbiology, and Forensic Medicine, The University of Jordan, Amman, Jordan.
Anas H. A. Abu-Humaidan
Department of Pathology, Microbiology, and Forensic Medicine, The University of Jordan, Amman, Jordan
Nisreen Abu Shahin
Department of Pathology, Microbiology, and Forensic Medicine, The University of Jordan, Amman, Jordan
Sachin Kote
International Centre for Cancer Vaccine Science, University of Gdansk, Gdansk, Poland
Moureq R. Alotaibi
Department of Pharmacology and Toxicology, King Saud University, Riyadh, Saudi Arabia
Moath Alrjoub
Department of Pathology and Microbiology, Jordan University of Science and Technology, Irbid, Jordan
Ahmad Altarifi
Department of Pharmacology, Jordan University of Science and Technology, Irbid, Jordan
Yazan Al Dweiri
Department of Biomedical Engineering, College of Engineering, Abu Dhabi University, Khalifa City, Abu Dhabi, UAE
