Cited by 79Cancer Treatment and PharmacologyMicrotubule and mitosis dynamicsDrug Transport and Resistance Mechanisms

Src family kinases and paclitaxel sensitivity

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Le, Xiao-Feng, Bast, Jr., Robert C.·2011·Cancer Biology & Therapy

Abstract

Src-family Kinases (SFKs) participate in the regulation of proliferation, differentiation, apoptosis, autophagy, adhesion, migration, invasion and angiogenesis in normal and cancer cells. Abnormal expression of SFKs has been documented in cancers that arise in breast, colon, ovary, melanocyte, gastric mucosa, head and neck, pancreas, lung, and brain. Targeting SFKs in cancer cells has been shown to be a promising therapeutic strategy in solid tumors, particularly in ovarian, colon and breast cancers. Paclitaxel is one of most widely used chemotherapeutic agents for the management of ovarian, breast, lung and head/neck cancers. As a microtubule-stabilizing agent, paclitaxel possesses both mitosis-dependent and mitosis-independent activities against cancer cells. A variety of mechanisms such as deregulation of P-glycoprotein, alteration of tubulin isotypes, alteration of microtubule-regulatory proteins, deregulation of apoptotic signaling pathways, mutation of tubulins and overexpression of copper transporters have been implicated in the development of primary or secondary resistance to paclitaxel. By affecting cancer cell survival, proliferation, autophagy, microtubule stability, motility, and/or angiogenesis, SFKs interact with mechanisms that regulate paclitaxel sensitivity. Inhibition of SFKs can potentiate the anti-tumor activity of paclitaxel by enhancing apoptosis, autophagy and microtubule stability. Based on pre-clinical observations, administration of SFK inhibitors in combination with paclitaxel could improve treatment for ovarian, breast, lung and head/neck cancers. Identification and validation of predictive biomarkers could also permit personalization of the therapy.

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Crossref · 10.4161/cbt.12.4.16430

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  • Preclinical evidence in sarcoma and ovarian cancer cell lines suggests that activation of Src reduces sensitivity to various chemotherapeutic drugs, including platinum agents, and that this resistance can be reversed by pharmacological inhibition.

    “In addition, evidence from preclinical studies in sarcoma and ovarian cancer cell lines suggests that activation of Src reduces sensitivity to various chemotherapeutic drugs, including platinum agents, and that this resistance can be reversed by pharmacological inhibition [19, 20][21–23][24].”

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Research works printed but not linked: 1

  1. Verbeek BS, Vroom TM, Adriaansen-Slot SS, Ottenhoff-Kalff AE, Geertzema JG, Hennipman A, et al. c-Src protein expression is increased in human breast cancer. An immunohistochemical and biochemical analysis. J Pathol 1996; 180:383-8. 0

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Authors
Le, X.-F., & Bast, Jr.
Affiliations
  • The University of Texas MD Anderson Cancer Center (US)
  • University of Texas MD Anderson Cancer Center, Houston, TX USA
Corresponding author
Le, Xiao-Feng
Venue
Cancer Biology & Therapy
Published
2011-08-15
Volume
12
Issue
4
Pages
260-269
ISSN
  • 1538-4047 (ISSN-L)
  • 1555-8576
OpenAlex
W2119168587
Cited by
79
References
173
Citations by year
2026: 1 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 8 · 2019: 3 · 2018: 5 · 2017: 6 · 2016: 11 · 2015: 10 · 2014: 8 · 2013: 6 · 2012: 4
FWCI
0.53
Type
journal article
Language
en
Open access
Locations
  • Cancer Biology & Therapy (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of Texas MD Anderson Cancer Center (#CA16672, P50 CA83639, P30CA 16672, NCI P50 CA 83639)
  • National Cancer Institute (P30CA16672, NCI P50 CA 83639, CA-16672, CA 83639, P50-CA83639, P50CA083639, P30CA016672)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
Src family kinases, paclitaxel, drug sensitivity, drug resistance, microtubule stabilization, apoptosis, autophagy, P-glycoprotein, tubulin, copper transporters, combination therapy, predictive biomarkers, ovarian cancer, breast cancer, lung cancer, head and neck cancer
MeSH terms
Antineoplastic Agents, Phytogenic, Enzyme Inhibitors, Humans, Neoplasms, Apoptosis, Paclitaxel, Drug Resistance, Neoplasm, src-Family Kinases, RNA Interference, Cell Line, Tumor

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