Tyrosine kinases are implicated in tumorigenesis and progression, and have emerged as major targets for drug discovery. Tyrosine kinase inhibitors (TKIs) inhibit corresponding kinases from phosphorylating tyrosine residues of their substrates and then block the activation of downstream signaling pathways. Over the past 20 years, multiple robust and well-tolerated TKIs with single or multiple targets including EGFR, ALK, ROS1, HER2, NTRK, VEGFR, RET, MET, MEK, FGFR, PDGFR, and KIT have been developed, contributing to the realization of precision cancer medicine based on individual patient’s genetic alteration features. TKIs have dramatically improved patients’ survival and quality of life, and shifted treatment paradigm of various solid tumors. In this article, we summarized the developing history of TKIs for treatment of solid tumors, aiming to provide up-to-date evidence for clinical decision-making and insight for future studies.
Despite the demonstrated benefit from epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) based therapies, EGFR mutant lung adenocarcinoma will eventually acquire drug resistance. Transformation to small-cell lung cancer (SCLC) is considered to be a rare resistance mechanism of EGFR-TKI therapy.We describe a case of a 46-year-old man presenting with refractory cough. Percutaneous transthoracic biopsy was performed and confirmed an EGFR exon 21 L858R lung adenocarcinoma. However, the patient relapsed after successful treatment with gefitinib for 1 year, at which point rebiopsy identified an SCLC and chemotherapy composed of platinum and pemetrexed was started. However, despite the brief success of chemotherapy, our patient died of aggressive cancer progression and complications of chemotherapy.Our case highlights the importance of rebiopsy when managing drug resistance and presents a possible origin of the transformed cells. We also summarize the clinical characteristics of cases involving transformed SCLC from previous studies and discuss whether it could be a new subtype of SCLC.
The difference in clinical features and treatment outcomes between localized sinonasal diffuse large B cell lymphoma (SN-DLBCL) and sinonasal extranodal NK/T cell lymphoma (SN-ENKTL) is unclear. Therefore, we analyzed a total of 47 patients with localized SN-DLBCL and 211 patients with localized SN-ENKTL. The age distribution for these two subtypes is very distinct and the B symptoms were more common in SN-ENKTL. However, both SN-DLBCL and SN-ENKTL patients could achieve high overall response rate (ORR) and favorable prognoses. The 3-year overall survival (OS) rates for patients with SN-DLBCL and SN-ENKTL were 79.7 and 83.6% (p = 0.707), and the 3-year progression-free survival (PFS) rates were 61.4 and 70.1% (p = 0.294), respectively. For SN-DLBCL patients, chemotherapy followed by involved-field radiotherapy (IFRT) resulted in higher OS (83.7 vs 62.5%) and PFS (63.9 vs 50.0%) compared with chemotherapy alone, but the difference was not significant. No significant difference was found in the OS or PFS between radiotherapy alone and radiotherapy combined with chemotherapy for all patients with SN-ENKTL. But in extensive stage I and stage II SN-ENKTL patients, radiotherapy combined with chemotherapy could significantly improve the PFS (73.8 vs 50.0%) compared with radiotherapy alone. These results indicate that remarkable clinical disparities exist between localized SN-DLBCL and SN-ENKTL. However, different treatment strategies for them can result in similarly favorable prognoses.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0368-9) contains supplementary material, which is available to authorized users.
Increasing knowledge on the hallmark characteristics of cancer and tumor pharmacology has promoted the introduction of phytochemicals, such as traditional Chinese medicine (TCM) in cancer therapy, which modulate numerous molecular targets and exert anticancer activities. β-elemene, an active and non-toxic compound isolated from the Chinese medicinal herb Rhizoma Zedoariae, has been explored as a potent anti-cancer agent against multiple cancers in extensive clinical trials and experimental research in vivo and in vitro. β-elemene exerts therapeutic potential via modulation of core hallmark capabilities of cancer by suppressing proliferative signaling, such as MAPK and PI3K/Akt/mTOR pathway, inducing cell death, up-regulating growth suppressors, deactivating invasion and metastasis and interacting replicative immortality and attenuating angiogenesis. Recent studies have significantly improved our understanding of anti-cancer activities and underlying molecular mechanisms of this Chinese medicine. This review presents these novel findings regarding the unique properties of β-elemene as an agent for cancer treatment, with an emphasis on multi-targeting biological and molecular regulation.
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