Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

c-Src Family of Tyrosine Kinases

Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_54


 ASV;  c-SRC;  p60-Src;  SRC;  SRC1

Historical Background

In 1911, pathologist Francis Peyton Rous isolated a virus from a Plymouth Rock chicken that has continued to bear his name, the Rous sarcoma virus (RSV) (Rous 1911). Rous sarcoma virus is the archetypal retrovirus, capable of causing tumors in chickens and rapidly transforming cells in culture with high efficiency through production of the protein viral sarcoma (v-Src), the first identified transforming protein. In 1976, Bishop and Varmus demonstrated that the v-Src gene has a normal cellular homolog gene (protooncogene), c-Src, and that the v-Src gene product, pp60v-Src or v-Src, is a phosphoprotein with an apparent molecular mass of 60 kDa with intrinsic protein kinase activity (Stehelin et al. 1976). Sequencing of the chicken c-Src gene and the RSV v-Src gene demonstrated that the two genes are closely related except at the C-terminal end, and it is this structural difference that leads to constitutive activation of v-Src, which underlies its transforming capacity (Takeya and Hanafusa 1983).

c-Src is the prototypic member of a family of non-receptor, membrane-associated tyrosine kinases comprising 11 c-Src family kinases (SFKs); the other ten are Fyn, Yes, Blk, Yrk, Frk (also known as Rak), Fgr, Hck, Lck, Srm, and Lyn (Sen and Johnson 2011). The human genome contains a Yes pseudogene known as YESps. c-Src, Yes, and Fyn are ubiquitously expressed in a variety of tissues. Srm is found in keratinocytes, whereas Blk, Fgr, Hck, Lck, and Lyn are found primarily in hematopoietic cells. Frk occurs chiefly in bladder, breast, brain, colon, and lymphoid cells. In fact, Frk has been shown to be a nuclear protein with growth-inhibitory effects when ectopically expressed in breast cancer cells. Blk occurs chiefly in colon, prostate, and small intestine cells, but it was initially isolated from a breast cancer cell line.

SFKs are activated by cytokine receptors, receptor protein tyrosine kinase, G-protein coupled receptors, and integrins. They promote cancer cell proliferation, survival, motility, and invasiveness (Summy and Gallick 2003).


SFKs are proteins of approximately 60 kDa composed of several functional domains: (a) a myristic acid moiety at the N-terminal region responsible for localization at the inner surface of the cell membrane; (b) a unique domain that provides unique functions and specificity to each member of the SFK family; (c) an SH3 domain that is able to bind proline-rich sequences to mediate both intracellular and intercellular interactions; (d) an SH2 domain that binds phosphorylated tyrosine residues on the SFK molecule itself or its substrates; (e) a linker domain that binds to the SH3 domain; and (f) a catalytic domain that is composed of two lobes separated by a catalytic cleft in which the ATP and substrate-binding sites reside and phosphate transfer occurs. The cleft forms an activation loop that contains tyrosine (Y419, c-Src, human) which is a positive regulatory site responsible for maximum kinase activity. The SFKs also include (g) the C-terminal tail, which contains a negative regulatory tyrosine (Y530, c-Src, human) residue (Fig. 1 and reviewed in Johnson and Gallick 2010).
c-Src Family of Tyrosine Kinases, Fig. 1

Cartoon representation of the structural domain of human-Src and viral-Src. Src is composed of an N′-terminal myristic acid chain attached to SH4 domain, a unique region followed by SH3 and SH2 domain. A short linker domain (L) followed by tyrosine kinase domain (SH1) harboring Tyr 419 and a C′-terminal regulatory domain (R) harboring Tyr 530. Viral Src differ from human Src in a number of ways with one major difference being the lack of a regulatory domain (R) at its C′-terminal end

Upon phosphorylation of Y530, the SFK attains a “closed” or inactive conformation by binding its C-terminal region to its SH2 domain. In this closed conformation, the activation loop adopts a compact structure, which fills the catalytic cleft and precludes access of ATP and substrate. The closed conformation masks the Y419 residue, furthermore, preventing activation by autophosphorylation (Fig. 2). Although c-Src and v-Src exhibit several single amino acid differences, the most striking difference is the substitution of the most C-terminal 19 amino acids of chicken c-Src (533 amino acids) by 12 completely different amino acids in RSV v-Src (526 amino acids) (Takeya and Hanafusa 1983). Following loss of the C-terminal negative regulatory Tyr residue, v-Src and v-Yes are no longer regulated by intramolecular interaction and become constitutively active.
c-Src Family of Tyrosine Kinases, Fig. 2

Schematic representation of Src kinase regulation by differential phosphorylation at kinase domain (Tyr 419) and C′-terminal regulatory domain (Tyr 530)

Regulation of c-Src Kinase Activity

v-Src is a constitutively activated form of c-Src capable of eliciting many dramatic biological responses, including adhesion, migration, invasion, proliferation, differentiation, and survival. Because of the extensive involvement of c-Src in multiple cellular processes (described below), investigators have searched for the mechanisms behind c-Src activation and discovered that many different processes can alter c-Src kinase activity.

Structure of the C-terminal Regulatory Domain

Phosphorylation of the C-terminal regulatory residue (Y530, c-Src) may be mediated by any of several kinases and phosphatases. As already described, phosphorylation of Y530, deletion or mutation of the C-terminal regulatory region, and displacement of the SH3 or SH2 domain mediated by intramolecular interactions regulate c-Src activity in cells. Because of the loss of the C-terminal negative regulatory Tyr residue, v-Src and v-Yes are no longer regulated by intermolecular interactions. Rare activating mutations in c-Src have been reported in some cases of advanced colon and endometrial cancers (Irby et al. 1999). These mutations result in a stop codon at 531, one residue beyond the Y530, resulting in a truncated c-Src that is unable to form the closed conformation.

Cytoplasmic Kinases

Two important protein tyrosine kinases in the phosphorylation of SFKs are c-Src kinase ( CSK) and its homolog CSK-homologous kinase ( CHK), which are both able to phosphorylate Y530. Substantial evidence suggests that CSK and CHK are negative regulators of SFKs that play distinct roles during development of the nervous system. Their distinct biological effects may be due to distinct signaling effects. Specifically, CHK was shown to enhance MAPK signaling, while the role of CSK was mediated predominantly by c-Src regulation. In cancer cells, CHK was able to downregulate ErbB-2/neu-activated Src kinases. CSK is structurally similar to c-Src, comprising an SH2 domain, an SH3 domain, and a tyrosine kinase domain, but it lacks the regulatory tyrosine residue at its C-terminal end. A number of proteins that specifically bind CSK and regulate its activity toward c-Src have been identified, including tyrosine-protein phosphatase non-receptor type 12 with a C-terminal PEST motif (PTP-PEST), which could potentially counteract the activity of CSK by dephosphorylating c-Src at Y530. Another mechanism of CSK regulation is through the transmembrane adapter protein Cbp (CSK-binding protein OR protein associated with glycosphingolipid-enriched microdomains (PAG)), which is a c-Src substrate. Following phosphorylation by c-Src, Cbp can bind to the SH2 domain of CSK, thus allowing its recruitment to the plasma membrane where active c-Src resides, creating a negative regulatory loop (Sen and Johnson 2011).

Protein Tyrosine Phosphatases

Several protein tyrosine phosphatases (PTPs) have been implicated in regulation of c-Src kinase activity, including PTP-alpha, PTP-gamma, SHP-1, SHP-2, and PTP-1B. PTP-alpha is ubiquitously expressed and enriched in brain tissue and is able to dephosphorylate both Y419 and Y530 in vitro in cancer cells (Zheng et al. 1992). However, it is unclear whether PTP-alpha acts as an activator or repressor molecule. Both c-Yes and c-Fyn are dephosphorylated and activated by PTP-alpha. In contrast, PTP-gamma is capable of dephosphorylating Y530 and is responsible for elevated c-Src kinase activity (Bjorge et al. 2000).

SHP-1 (also known as PTP-1 C) and SHP-2 are cytosolic, SH2 domain-containing PTPs expressed in epithelial and hematopoetic cells. They can dephosphorylate Y530 and subsequently increase c-Src kinase activity. The SH2 domain of SHP-2 binds to the SH3 domain of c-Src, which results in allosteric regulation of c-Src.

PTP-1B (also known as PTP-N1) was purified from breast cancer cells as a phosphatase that can dephosphorylate a Y530-containing peptide (Bjorge et al. 2000). Biochemical analysis showed that cancer cells have elevated levels of PTP activity, which correlates with reduced phosphorylation of the C-terminal residue of c-Src and may have an important role in controlling c-Src kinase activity.

Membrane-Associated Receptors and Cytoplasmic Kinases

c-Src can act as an upstream or downstream modulator of receptor molecules, including receptor tyrosine kinases (RTKs), steroid hormone receptors, and G-protein coupled receptors (GPCR). c-Src can also be activated by non-receptor tyrosine kinases.

SFKs physically interact with activated RTKs, creating a positive regulatory loop that contributes to robustness of RTK signaling. Upon stimulation by its ligands, RTKs cause receptor dimerization and autophosphorylation of tyrosine residues of the cytoplasmic domain. The resulting phosphorylation acts as a docking site to recruit and activate c-Src, which in turn phosphorylates other RTKs and creates other SH2 binding recruitment sites, allowing binding of the Grb2-SOS complex leading to activation of downstream signaling of the Ras-MAPK and PI3K signaling pathways. c-Src can associate with overexpressed epidermal growth factor receptor (EGFR) to cause synergistic mitogenicity. c-Src activity can be stimulated by EGFR autophosphorylation of Tyr 845. EGF has been shown to stimulate invasion and metastasis of carcinoma cells through Src-mediated activation of  p130Cas. RTKs and integrins also act synergistically in promoting cell survival, proliferation, cytoskeletal reorganization, and invasion through signaling mediated by c-Src.

The binding of SFKs to various proteins plays important roles in SFK regulation. Several structural features of SFKs facilitate their interactions with proteins that regulate them. X-ray crystal structure analysis revealed that the inactive Src conformation can be achieved by interaction between the SH2 domain and the C-terminal Tyr residue or between the SH3 domain and the SH2 kinase linker. A variety of Src-binding proteins can compete for binding in this cleft, disrupting the intramolecular interaction and activating c-Src. Platelet-derived growth factor receptor (PDGFR) and focal adhesion kinase (FAK) can bind to the c-Src SH2 domain and activate c-Src and Hck (another member of SFK). p130Cas can bind to the c-Src SH2 and SH3 domains, activating c-Src.

Increased Expression and Altered Protein Stability

Recent evidence suggests that c-Src is subject to ubiquitin-dependent degradation. Specifically, activated forms of c-Src are turned over more rapidly than inactive c-Src. One possible explanation is that c-Src and Fyn bind to and phosphorylate c-Cbl. Upon binding with c-Src, c-Cbl acts as an E3-ubiquitin ligase, leading to c-Src degradation (Frame 2002).

SFK Regulation of Cancer Cell Function

SFKs are important in various aspects of tumor development, including proliferation, migration, invasiveness, apoptosis, and angiogenesis. It is well documented that c-Src is responsible for dynamic regulation of the actin cytoskeleton, resulting in cell motility, cell membrane adhesion, and cell-cell adhesion. c-Src acts as one of the central components of the focal adhesion complex. The c-Src SH3 domain associates with actin filaments upon activation, which then drive translocation of c-Src to cell-cell and cell-matrix adhesion sites where c-Src can interact with plasma membrane-bound molecular partners to take part in two major transduction events: signaling from RTKs, which mainly affects cell growth, proliferation, and migration; and signaling from adhesion receptors such as integrins and E-cadherin, which mainly regulates cytoskeletal functions (Fig. 3 and reviewed in (Johnson and Gallick 2010)).
c-Src Family of Tyrosine Kinases, Fig. 3

Cartoon representation of Src signaling in tumor development and progression

SFKs are frequently overexpressed and/or aberrantly activated in a variety of cancers. The contributions of c-Src to cell regulation and cancer development were discussed by Summy and Gallick (2003). Activation is very common in colorectal and breast cancers and less frequent in melanomas and ovarian, gastric, head and neck, pancreatic, lung, brain, and hematologic cancers. The extent of increased SFK activity often correlates with malignant features and patient survival.

Colon Cancer

Involvement of c-Src in cancer development and progression has been studied more extensively in colon cancer than in any other human cancer. c-Src kinase activity is elevated in premalignant ulcerative colitis lesions, and lesions with the highest extent of dysplasia have the greatest potential for progression to carcinoma. Surprisingly, adenomas displayed stronger immunohistochemical staining for active c-Src than advanced adenocarcinomas (Summy and Gallick 2003).

c-Src-specific kinase activity via phosphorylation is elevated in colon cancer cell lines. Although c-Src is frequently activated in human colon cancers, it is not the only SFK whose activation corresponds with malignant progression. c-Yes is also frequently activated in colon cancers. c-Yes kinase activity was elevated in three of five colon cancer cell lines and 10 of 21 primary colon carcinomas relative to normal colonic mucosa (Summy and Gallick 2003). Because of the high homology between c-Src and c-Yes, it has been assumed that both kinases perform similar functions in cancer development, but c-Yes is evidently unable to compensate fully for the lack of c-Src in these processes because of its substrate specificity among different SFKs. Regulation of actin cytoskeleton dynamics is crucial to the motility, invasiveness, and metastatic spread of tumor cells, and thus the contribution of c-Yes to tumor development may differ from that of c-Src. Interestingly, Lck is also expressed in colon cancer as a result of abnormal activation of the Lck promoter due to loss of its transcriptional repressor.

Treatment of a human colon tumor cell line with tyrosine kinase inhibitor herbimycin-A caused a reduction in c-Src kinase activity followed by subsequent reduction in colon cancer cell growth. c-Src kinase activity as measured by phosphorylated Y419 is important for proliferation and growth of primary tumors derived from human colon cancer cells. SFKs may contribute to the invasiveness of colon carcinoma cells through dynamic regulation of the actin cytoskeleton and activation of matrix proteases. c-Src expression also regulates the cadherin-catenin association, thereby regulating cell-cell contact. Another report suggested that the level of vascular endothelial growth factor (VEGF) varied directly with c-Src level in a colon cancer cell line (Johnson and Gallick 2010; Summy and Gallick 2003).

Breast Carcinoma

Considerable data support a role for SFKs in the progression of breast cancer. Several independent reports have demonstrated elevated levels of c-Src kinase activity in breast carcinoma tissue in comparison to normal breast epithelium. Lehrer et al. showed that tumors expressing the progesterone receptor generally displayed higher kinase activity than those that did not express progesterone receptor and that 70% of tyrosine kinase activity in breast cancer could be attributed to c-Src (Lehrer et al. 1989). Female mice with forced expression of active c-Src frequently developed epithelial hyperplasia, which occasionally progressed to full neoplasia. As with colon cancer, c-Src is important in the induction of VEGF transcription in breast cancer, suggesting the importance of c-Src in cancer angiogenesis.

Zhang et al. provided both clinical and experimental evidence that c-Src plays a critical role in establishment of latent bone metastasis in breast cancer. Using a bioinformatic approach, they identified a c-Src activity gene expression signature that was highly associated with the late onset of bone metastasis in breast cancer (Zhang et al. 2009).


Human melanoma is one of the few cancers in which c-Yes plays a more crucial role in the cancer development than c-Src. c-Yes kinase activity is increased in melanoma cells compared to normal melanocytes, but c-Src kinase activity is not upregulated. Likewise, c-Yes is activated in the presence of nerve growth factor, whereas c-Src is not (Johnson and Gallick 2007).

Head and Neck Cancer

c-Src is expressed in Barrett’s esophagus and esophageal adenocarcinoma as well as other head and neck cancers. c-Src is overexpressed in hyperproliferating regions of head and neck squamous cell carcinoma (HNSCC), dysplastic epithelium, papillomas, and inflamed normal tissues (Summy and Gallick 2003). Inhibition of c-Src leads to a universal decrease in HNSCC cell invasion, with more modest and variable effects on cell cycle arrest and apoptosis (Johnson et al. 2005). c-Src inhibition in HNSCC leads to reactivation of pSTAT3 expression, which is considered a mechanism for cellular resistance toward c-Src inhibitors (Sen et al. 2009). c-Src activity regulates invadopodia formation in HNSCC cell lines, thereby increasing invasiveness (Kelley et al. 2010). It has been shown that c-Src along with c-Met plays an important role in survival of head and neck cancer cells and that c-Met acts as direct c-Src substrate in HNSCC, which suggest that Src-dependent cell survival is also regulated by c-Met receptor activation (Sen et al. 2011).

Pancreatic Cancer

c-Src overexpression and increased c-Src kinase activity were observed in pancreatic cancer cell lines but not in normal pancreatic cells. Activated c-Src expression in pancreatic carcinoma cells results in elevated expression of the insulin-like growth factor-1 (IGF-1) receptor, which leads to increased IGF-1-dependent cell proliferation. c-Src-mediated reciprocal regulation of E-cadherin expression also correlated with growth and progression of human pancreatic cancers (Summy and Gallick 2003).

Ovarian Cancer

c-Src may play very specific roles in the progression of ovarian cancer. c-Src expression is required for anchorage-independent growth and angiogenesis in ovarian cancer. c-Src activity appears to be important for SHC phosphorylation and Erk1/2 phosphorylation downstream of CXCR1/2 receptor stimulation in ovarian cancer (Summy and Gallick 2003). It has also been reported that c-Src inhibition enhanced paclitaxel cytotoxicity in ovarian cancer cells by caspase 9-independent activation of caspase 3. Recent data show the importance of c-Src and protein kinase G-alpha interaction in promoting DNA synthesis and cell proliferation in human ovarian cancer cells (Leung et al. 2010).

Bladder Cancer

c-Src kinase activity is upregulated in human bladder carcinoma cells. c-Src is involved in the epithelial-to-mesenchymal transition of bladder cancer cells in a rat bladder carcinoma model. Increased caveoline-1 expression and decreased c-Src expression and kinase activity correlated with bladder tumor aggressiveness (Thomas et al. 2011).

Gastric Cancer

c-Src kinase activity is greater in gastric carcinoma tissues than in normal mucosal samples. In a subset of gastric cancer cell lines, c-Src inhibition led to increased cell cycle arrest and apoptosis. The resistant gastric carcinoma cell lines had c-Met amplification, suggesting that this pathway is a possible mechanism of resistance (Okamoto et al. 2010).

Lung Cancer

Increased expression of c-Src has been reported in 60–80% of adenocarcinomas and bronchioloalveolar cancers and in 50% of squamous cell carcinomas isolated from patients with non-small cell lung cancer (NSCLC). High levels of c-Src kinase activity in NSCLC correlate with tumor size. The mitogenic effects of both nicotine and asbestos are mediated through c-Src. c-Src-mediated constitutive  STAT3 activity has been found in multiple NSCLC cell lines. c-Src inhibition leads to STAT3 activation in multiple NSCLC cell lines, which is believed to be the alternative resistance mechanism for NSCLC cell survival upon c-Src inhibition (Byers et al. 2009). Studies have shown that activation of STAT3 and FAK by c-Src is required for anchorage-dependent and -independent growth in a range of human tumors, including NSCLC. Furthermore, stimulation of STAT3 by EGF, IL6, and hepatocyte growth factor in NSCLC all required c-Src activity. c-Src also activates the VEGF pathway via STAT3 (Johnson and Gallick 2007).

In human NSCLC, c-Src activity is associated with inhibition of anoikis, a form of cell death induced by detachment of adherent cells from the substratum. Following detachment from the primary tumor, c-Src activity is increased, which is able to compensate for the loss of survival signals from cell matrix. Under hypoxic conditions, SFK-dependent transcriptional upregulation of the endothelial PAS-domain protein-1 was observed. These data indicate that SFKs may be involved in regulation of signaling pathways that govern multiple aspects of lung cancer progression (Johnson and Gallick 2007; Summy and Gallick 2003).

Leukemia and Lymphoma

The SFK Lyn is expressed in lymphocytes and monocytes. Lyn was specifically activated in myeloid leukemia cell lines in response to IL3. Lyn is also responsible for phosphorylation of B-cell receptor (BCR) and its coreceptors Ig-alpha and Ig-beta. Lyn is also involved in IL6-mediated cell proliferation. Lck is expressed in T lymphocytes and plays an important role in T-cell hematopoiesis, proliferation, and receptor signaling (Johnson and Gallick 2007).

Clinical Trials with c-Src Inhibitors

Because of the extensive literature supporting the importance of c-Src in tumor progression, angiogenesis, and metastasis, as well as positive correlations between c-Src expression and cancer progression, c-Src is emerging as a promising target for anticancer therapy. Several small-molecule inhibitors of c-Src kinases are undergoing clinical trials after promising preclinical studies, such as the ATP-binding competitive inhibitors dasatinib (BMS-354825, Sprycel), bosutinib (SKI-606), ponatinib (AP24534), and bafetinib (INNO-406), and the substrate binding-site inhibitor Kxo-I (KX2-391) (Sen and Johnson 2011).

Dasatinib (BMS-354825; Bristol-Myers Squibb, New York, NY), an oral inhibitor of Abl, cKit, SFKs, PDGFR, Btk, Ephrin receptor A2 (EphA2), and other kinases, is currently used in the treatment of Bcr-Abl-positive leukemia and gastrointestinal stromal tumor. It is well tolerated by humans. It suppresses the invasion of HNSCC, NSCLC, and other epithelial cancers in vitro (Johnson and Gallick 2010). It is also able to greatly inhibit development of metastasis in an orthotopic mouse model of pancreatic cancer. The triple-negative subtype and EGFR-overexpressing breast cancer cell lines were particularly sensitive to dasatinib (Rothschild et al. 2010; Sen and Johnson 2011). On the basis of promising results of a phase I/II trial of the combination of dasatinib and docetaxel in patients with castration-resistant prostate cancer, this combination is now being studied in a phase III clinical trial (Rothschild et al. 2010). A phase I study of dasatinib in combination with capecitabine or paclitaxel has shown promising results in breast cancer patients. In a phase II study with dasatinib as a single agent in NSCLC had modest clinical activity that was lower than that generally observed in patients who receive standard chemotherapy. Marked activity in one patient and prolonged stable disease in four others suggested a potential subpopulation of patients with dasatinib-sensitive NSCLC (Johnson et al. 2010). Partial responses have been observed in a phase I/II study of dasatinib in combination with erlotinib in advanced NSCLC (Haura et al. 2010). Single-agent dasatinib failed to demonstrate significant activity in patients with advanced HNSCC, despite durable c-Src inhibition (Brooks et al. 2011).

Bosutinib (SKI 606; Wyeth Pharmaceuticals Inc., Madison, NJ) is an oral inhibitor of SFKs and Abl, with a lower affinity for cKit and PDGFR than dasatinib. It showed promising results in a colon cancer murine model and was well tolerated. In preclinical studies, bosutinib resulted in a dose-dependent reduction in proliferation, invasion, and migration of breast cancer cells. In a breast cancer mouse model, bosutinib significantly reduced metastasis to liver, spleen, and lung (Rothschild et al. 2010). In phase II trials, bosutinib either as single agent or in combination with exemestane, letrozole/capecitabine, or zolendronic acid has been well tolerated in patients with advanced breast cancer and has shown promising results (Sen and Johnson 2011).

Saracatinib (AZD 0530; AstraZeneca Pharmaceuticals, London, UK) is an oral inhibitor of SFKs and Abl. Despite promising preclinical studies, AZD0530 was withdrawn from further clinical development, likely because of its lack of clinical efficacy in multiple studies.

Other ATP-competitive tyrosine kinase inhibitors aimed at multiple targets, including SFKs, are being evaluated. XL999 is an oral inhibitor of SFKs, VEGFR, PDGFR, fibroblast growth factor receptor (FGFR), and fms-related tyrosine kinase 3 (FLT3) and has shown activity against solid tumors in phase I and phase II trials. XL228 targets the IGF receptor 1, aurora kinase, FGFR, and Abl. M475271 is another oral kinase inhibitor of c-Src and VEGFR that showed preclinical activity in lung adenocarcinoma cell lines. KX2-391 is an SFK inhibitor that targets the peptide substrate-binding site rather than the ATP-binding site of c-Src. It is not a tyrosine kinase inhibitor. It appears to have a wide spectrum of antitumor activity that is distinct from that of other tyrosine kinase inhibitors. In a phase I trial in patients with advanced solid tumors, KX2-391 was well tolerated (Rothschild et al. 2010).


A wealth of data indicates the importance of SFKs in the growth and development of various types of human cancers. The structure of c-Src and the mode of its regulation have been studied extensively since its discovery. To clarify and fully elucidate the normal physiological functions of c-Src and other SFKs, their interactions with specific substrates and binding partners in different subcellular environments should be characterized in detail. Phase I and phase II studies of c-Src inhibitors as single agents or in combination regimens in lung cancer, breast cancer, and prostate cancer are promising and warrant further investigation. A detailed comprehensive understanding is needed for the available inhibitors to improve our current approach to cancer therapy.


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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Thoracic/Head and Neck Medical Oncology, Unit 432The University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.The University of Texas Graduate School of Biomedical Sciences at HoustonHoustonUSA