Strategies for overcoming resistance to EGFR family tyrosine kinase inhibitors.


:The first-generation epidermal growth factor receptor tyrosine kinase inhibitors erlotinib and gefitinib have been incorporated into treatment paradigms for patients with advanced non-small cell lung cancer. These agents are particularly effective in a subset of patients whose tumors harbor activating epidermal growth factor receptor mutations. However, most patients do not respond to these tyrosine kinase inhibitors, and those who do will eventually acquire resistance that typically results from a secondary epidermal growth factor receptor mutation (e.g., T790M), mesenchymal-epithelial transition factor amplification, or activation of other signaling pathways. For patients whose tumors have wild-type epidermal growth factor receptor, there are several known mechanisms of initial resistance (e.g., Kirsten rat sarcoma viral oncogene homolog mutations) but these do not account for all cases, suggesting that unknown mechanisms also contribute. To potentially overcome the issue of resistance, next-generation tyrosine kinase inhibitors are being developed, which irreversibly block multiple epidermal growth factor receptor family members (e.g., afatinib [BIBW 2992] and PF-00299804) and/or vascular endothelial growth factor receptor pathways (e.g., BMS-690514 and XL647). In addition, drugs that block parallel signaling pathways or signaling molecules downstream of the epidermal growth factor receptor, such as the insulin-like growth factor-1 receptor and the mammalian target of rapamycin, are undergoing clinical evaluation. As drug resistance appears to be pleomorphic, combinations of drugs or drugs with multiple targets may be more effective in circumventing resistance.


Cancer Treat Rev


Cancer treatment reviews


Giaccone G,Wang Y




Has Abstract


2011-10-01 00:00:00














  • Adjuvant immunotherapy for non-small cell lung cancer.

    abstract::Non-small cell lung cancer (NSCLC) is the biggest cancer killer in the United States and worldwide. In 2011, there are estimated to be 221,130 new cases of lung cancer in the United States. Over a million people will die of lung cancer worldwide this year alone. When possible, surgery to remove the tumor is the best t...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Tucker ZC,Laguna BA,Moon E,Singhal S

    更新日期:2012-10-01 00:00:00

  • Determinants and associated factors influencing medication adherence and persistence to oral anticancer drugs: a systematic review.

    abstract:BACKGROUND AND AIMS:The use of oral anticancer drugs has increased in modern oncology treatment. The move from intravenous treatments towards oral anticancer drugs has increased the patients' own responsibility to take oral anticancer drugs as being prescribed. High rates of non-adherence to oral anticancer drugs have ...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Verbrugghe M,Verhaeghe S,Lauwaert K,Beeckman D,Van Hecke A

    更新日期:2013-10-01 00:00:00

  • Low dose cyclophosphamide: Mechanisms of T cell modulation.

    abstract::Cyclophosphamide is considered one of the most successful chemotherapy drugs and is listed on the World Health Organisations List of Essential Medicines. Since its initial synthesis in 1958, it has been widely used to treat a range of cancers but its use has been declining due to the advent of platinum based and other...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Madondo MT,Quinn M,Plebanski M

    更新日期:2016-01-01 00:00:00

  • Irreversible pan-ErbB tyrosine kinase inhibitors and breast cancer: current status and future directions.

    abstract::Aberrant activation of HER2 through overexpression has been shown to play an important role in some breast cancers. Therapies against this receptor including the monoclonal antibody, trastuzumab, or the small tyrosine kinase inhibitor, lapatinib have shown to improve the prognosis of such patients. Despite overexpress...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Ocaña A,Amir E

    更新日期:2009-12-01 00:00:00

  • Early diagnosis and surgical management of prostate cancer.

    abstract::Prostate cancer is a significant cause of morbidity and mortality in the United States and Europe. The natural ageing of the population as well as the continued and widespread use of diagnostic tests such as prostate specific antigen (PSA), has led to an increase in the numbers of men diagnosed with localised prostate...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Linton KD,Hamdy FC

    更新日期:2003-06-01 00:00:00

  • Practical management of tyrosine kinase inhibitor-associated side effects in GIST.

    abstract::Patients diagnosed with advanced gastrointestinal stromal tumor (GIST) are currently treated with oral tyrosine kinase inhibitors (TKIs). Imatinib mesylate is the standard first-line treatment, and sunitinib malate is administered second-line for patients who are intolerant or progress on imatinib. Imatinib has recent...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Joensuu H,Trent JC,Reichardt P

    更新日期:2011-02-01 00:00:00

  • Pegylated liposomal doxorubicin (Caelyx) in recurrent ovarian cancer.

    abstract::Epithelial ovarian cancer (EOC) is the most common gynaecological malignancy in the Western world and a leading cause of death. Patients with relapsed EOC are incurable and therefore the toxicity of palliative chemotherapy and effects on health-related Quality of Life are important factors. Several newer cytotoxic age...

    journal_title:Cancer treatment reviews

    pub_type: 临床试验,杂志文章,随机对照试验,评审


    authors: Stebbing J,Gaya A

    更新日期:2002-04-01 00:00:00

  • Radionuclide treatment of painful bone metastases in patients with breast cancer: a systematic review.

    abstract::Bone-seeking radionuclides, such as Sr-89, Sm-153, and Re-186, have been shown to have an effect on pain from bone metastasis in prostate cancer. The effect on bone pain in other cancer types, including breast cancer, remains unclear. The purpose of the study was to perform a systematic review of the use of radioisoto...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,随机对照试验,评审


    authors: Christensen MH,Petersen LJ

    更新日期:2012-04-01 00:00:00

  • Rectal and colon cancer: Not just a different anatomic site.

    abstract::Due to differences in anatomy, primary rectal and colon cancer require different staging procedures, different neo-adjuvant treatment and different surgical approaches. For example, neoadjuvant radiotherapy or chemoradiotherapy is administered solely for rectal cancer. Neoadjuvant therapy and total mesorectal excision...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Tamas K,Walenkamp AM,de Vries EG,van Vugt MA,Beets-Tan RG,van Etten B,de Groot DJ,Hospers GA

    更新日期:2015-09-01 00:00:00

  • Prognostic, predictive and therapeutic implications of HER2 in invasive epithelial ovarian cancer.

    abstract::The HER2 oncogene encodes a transmembrane protein partially homologous to epidermal growth factor receptor. This oncogene has been studied mainly in breast cancer where it has prognostic, predictive and therapeutic target value. The expression of HER2 in epithelial ovarian cancer has been less studied. HER2 expression...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Serrano-Olvera A,Dueñas-González A,Gallardo-Rincón D,Candelaria M,De la Garza-Salazar J

    更新日期:2006-05-01 00:00:00

  • Advances in neoadjuvant therapy for colorectal cancer with liver metastases.

    abstract::Metastatic colorectal cancer (CRC) is most frequently seen in the liver. Resection of metastases remains the treatment of choice; however, the majority of patients are ineligible for surgery due to unfavorable location, size, or number of metastases; insufficient liver reserve; or extrahepatic disease. The activity of...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Pozzo C,Barone C,Kemeny NE

    更新日期:2008-06-01 00:00:00

  • Prognostic value of lymphocyte-to-monocyte ratio in patients with solid tumors: A systematic review and meta-analysis.

    abstract:BACKGROUND:The immune system plays an important role in cancer pathogenesis. A low lymphocyte-to-monocyte ratio (LMR), as a simple biomarker of host immune system, has been suggested to be related to poor prognosis in various cancers. We performed a systematic review and meta-analysis to quantify the prognostic value o...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,meta分析,评审


    authors: Nishijima TF,Muss HB,Shachar SS,Tamura K,Takamatsu Y

    更新日期:2015-12-01 00:00:00

  • Relevance of high-dose chemotherapy in solid tumours.

    abstract::Drug resistance is a major problem in the treatment of solid tumours. Based on a steep dose-response relationship for especially alkylating agents on tumour cell survival, high-dose chemotherapy was considered of interest for the treatment of solid tumours. Results of phase 1 and 2 studies with high-dose chemotherapy ...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Nieboer P,de Vries EG,Mulder NH,van der Graaf WT

    更新日期:2005-05-01 00:00:00

  • Treatment of small cell lung cancer in the elderly based on a critical literature review of clinical trials.

    abstract::At diagnosis, 25-40% of patients with small cell lung cancer (SCLC) are 70 years of age or older, and many of them have been undertreated because of fear of excessive toxicity associated with chemotherapy. Papers retrieved by a Medline search using the key words "elderly or older" and "small cell lung cancer" and by a...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Sekine I,Yamamoto N,Kunitoh H,Ohe Y,Tamura T,Kodama T,Saijo N

    更新日期:2004-06-01 00:00:00

  • An overview of neoadjuvant chemotherapy in the multimodality treatment of malignant pleural mesothelioma.

    abstract::Malignant Pleural Mesothelioma (MPM) is an aggressive tumour with poor prognosis and increasing incidence in industrialized countries because of the previous widespread exposure to asbestos fibres and to the long lag period from time of exposure and the diagnosis of the disease. MPM shows high refractoriety to systemi...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Pasello G,Ceresoli GL,Favaretto A

    更新日期:2013-02-01 00:00:00

  • A systematic review and meta-analysis of randomised trials of neo-adjuvant hormone therapy for localised and locally advanced prostate carcinoma.

    abstract:BACKGROUND:We performed a systematic review and meta-analysis of randomised trials of neo-adjuvant hormone therapy (NHT) in localised and locally advanced prostate cancer to assess the effectiveness of this therapy. METHODS:We searched MEDLINE, The Cochrane Library, Science Citation Index, LILACS and SIGLE for randomi...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,meta分析,评审


    authors: Shelley MD,Kumar S,Wilt T,Staffurth J,Coles B,Mason MD

    更新日期:2009-02-01 00:00:00

  • Targeting the PI3K/AKT/mTOR pathway in biliary tract cancers: A review of current evidences and future perspectives.

    abstract::Biliary tract cancers (BTCs) are a group of invasive neoplasms, with increasing incidence and dismal prognosis. In advanced disease, the standard of care is represented by first-line chemotherapy with cisplatin and gemcitabine. In subsequent lines, no clear recommendations are currently available, highlighting the nee...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Corti F,Nichetti F,Raimondi A,Niger M,Prinzi N,Torchio M,Tamborini E,Perrone F,Pruneri G,Di Bartolomeo M,de Braud F,Pusceddu S

    更新日期:2019-01-01 00:00:00

  • Rationale for the treatment of solid tumors with the proteasome inhibitor bortezomib.

    abstract::Given its role in cellular metabolism, the proteasome could prove to be a critical target that can be exploited in treating cancer. In preclinical studies, several mechanisms for bortezomib's activity in multiple myeloma cells have been identified (e.g., NF-kappaB inhibition); antitumor activity with bortezomib has be...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Cusack JC

    更新日期:2003-05-01 00:00:00

  • RAF signaling in neuroendocrine neoplasms: from bench to bedside.

    abstract::Neuroendocrine neoplasms are a low-incidence and heterogeneous group of malignancies. In the advanced stage, several therapeutic options can be discussed, including molecular-targeted agents, but biological predicting factors are lacking. A number of molecular targets have been studied over the last decade leading to ...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Fazio N,Abdel-Rahman O,Spada F,Galdy S,De Dosso S,Capdevila J,Scarpa A

    更新日期:2014-09-01 00:00:00

  • Update on capecitabine alone and in combination regimens in colorectal cancer patients.

    abstract::Capecitabine is an orally administered fluoropyrimidine carbamate which has been developed as a prodrug of 5-FU with the goal to improve its tolerability and intratumoral drug concentration. The review aims to provide an evidence-based update of clinical trials investigating the clinical efficacy, adverse-event profil...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Silvestris N,Maiello E,De Vita F,Cinieri S,Santini D,Russo A,Tommasi S,Azzariti A,Numico G,Pisconti S,Petriella D,Lorusso V,Millaku A,Colucci G

    更新日期:2010-11-01 00:00:00

  • The metabolic syndrome in long-term cancer survivors, an important target for secondary preventive measures.

    abstract::With increasing numbers of cancer survivors, attention has been drawn to long-term complications of curative cancer treatment, including a range of metabolic disorders. These metabolic disorders often resemble the components of the so-called metabolic syndrome, or syndrome X, which is an important risk factor for the ...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Nuver J,Smit AJ,Postma A,Sleijfer DT,Gietema JA

    更新日期:2002-08-01 00:00:00

  • Developments in the systemic treatment of metastatic cervical cancer.

    abstract::Despite the available prevention and early detection strategies, advanced squamous-cell carcinoma of the uterine cervix remains a major concern for public health. Systemic treatment with cisplatin, either in combination with external beam irradiation for locally advanced disease, or as monotherapy for recurrent/metast...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Mountzios G,Soultati A,Pectasides D,Pectasides E,Dimopoulos MA,Papadimitriou CA

    更新日期:2013-08-01 00:00:00

  • Neoadjuvant endocrine therapy in breast cancer.

    abstract::The use of endocrine therapy is well established as a primary treatment for locally advanced breast cancer. However, despite the current popularity of neoadjuvant chemotherapy for operable tumours, there is relatively little published evidence for pre-operative endocrine therapy in operable disease, particularly outsi...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Beresford MJ,Ravichandran D,Makris A

    更新日期:2007-02-01 00:00:00

  • Cancer surgery: the last 25 years.

    abstract::Surgery is, and always has been, the main treatment modality of solid tumours. For a long period, it consisted of a number of surgical procedures dictated by basic oncologic principles, most of which are still adhered to. Over the last few decades, increased understanding of the disease, new or improved diagnostic fac...

    journal_title:Cancer treatment reviews

    pub_type: 历史文章,杂志文章,评审


    authors: Bremers AJ,Rutgers EJ,van de Velde CJ

    更新日期:1999-12-01 00:00:00

  • Cancer stem cells niche: a target for novel cancer therapeutics.

    abstract::Nowadays, cancer has been a frequent disease, and the first or second most common cause of death worldwide. Despite a better understanding of the biology of cancer cells, the therapy of most cancers has not significantly changed for the past four decades. It is because conventional chemotherapies and/or radiation ther...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Yi SY,Hao YB,Nan KJ,Fan TL

    更新日期:2013-05-01 00:00:00

  • Electrochemotherapy of chest wall breast cancer recurrence.

    abstract::Chest wall breast cancer recurrence after mastectomy is a disease difficult to treat. Its incidence varies between 5% and 30% in different subset of patients. When possible, radical surgical therapy represents the main treatment approach, however when the disease progresses and/or treatments are not successful, ulcera...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Sersa G,Cufer T,Paulin SM,Cemazar M,Snoj M

    更新日期:2012-08-01 00:00:00

  • New approaches to the systemic treatment of melanoma.

    abstract::Metastatic melanoma is an incurable condition with a median survival of about 6 months. Chemotherapy can result in objective tumour responses but only in a minority of cases and remissions are short-lived, 3-6 months. DTJC is the most active single agent with response rates of 15-20% and although combination chemother...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Chowdhury S,Vaughan MM,Gore ME

    更新日期:1999-10-01 00:00:00

  • The role of the tumor-microenvironment in lung cancer-metastasis and its relationship to potential therapeutic targets.

    abstract::Non-small cell lung cancer (NSCLC) accounts for >80% of lung cancer cases and currently has an overall five-year survival rate of only 15%. Patients presenting with advanced stage NSCLC die within 18-months of diagnosis. Metastatic spread accounts for >70% of these deaths. Thus elucidation of the mechanistic basis of ...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Wood SL,Pernemalm M,Crosbie PA,Whetton AD

    更新日期:2014-05-01 00:00:00

  • Contemporary issues and the potential uses of capecitabine in metastatic breast cancer.

    abstract::Since its first regulatory approval more than 10 years ago, oncologists have gained wide experience in using the oral fluoropyrimidine, capecitabine, as monotherapy or in combination with other agents and the body of evidence supporting these approaches continues to grow. Alongside this increasing experience has been ...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: Barrett-Lee P,Bidard FC,Pierga JY

    更新日期:2009-11-01 00:00:00

  • SARS-CoV-2 and cancer: Are they really partners in crime?

    abstract::The outbreak of the SARS-CoV-2 pandemic has overwhelmed health care systems in many countries. The clinical presentation of the SARS-CoV-2 varies between a subclinical or flu-like syndrome to that of severe pneumonia with multi-organ failure and death. Initial reports have suggested that cancer patients may have a hig...

    journal_title:Cancer treatment reviews

    pub_type: 杂志文章,评审


    authors: van Dam PA,Huizing M,Mestach G,Dierckxsens S,Tjalma W,Trinh XB,Papadimitriou K,Altintas S,Vermorken J,Vulsteke C,Janssens A,Berneman Z,Prenen H,Meuris L,Vanden Berghe W,Smits E,Peeters M

    更新日期:2020-09-01 00:00:00