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Signal Transduction and Targeted Therapy May 2021Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since the... (Review)
Review
Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies. By December 2020, 89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China. Despite great progress, small-molecule targeted anti-cancer drugs still face many challenges, such as a low response rate and drug resistance. To better promote the development of targeted anti-cancer drugs, we conducted a comprehensive review of small-molecule targeted anti-cancer drugs according to the target classification. We present all the approved drugs as well as important drug candidates in clinical trials for each target, discuss the current challenges, and provide insights and perspectives for the research and development of anti-cancer drugs.
Topics: Antineoplastic Agents; Drug Approval; Drug Delivery Systems; Humans; Molecular Targeted Therapy; Neoplasms; Protein Kinase Inhibitors; Small Molecule Libraries; United States; United States Food and Drug Administration
PubMed: 34054126
DOI: 10.1038/s41392-021-00572-w -
American Family Physician Feb 2021Targeted cancer therapies involve chemotherapeutic agents that attack, directly or indirectly, a specific genetic biomarker found in a given cancer. Targeted oncology...
Targeted cancer therapies involve chemotherapeutic agents that attack, directly or indirectly, a specific genetic biomarker found in a given cancer. Targeted oncology includes monoclonal antibodies, small molecule inhibitors, antibody-drug conjugates, and immunotherapy. For example, the monoclonal antibodies trastuzumab and pertuzumab target human epidermal growth factor receptor 2 (HER2) and are used when treating HER2-positive breast cancer. Although targeted oncology has improved survival by years for some incurable cancers such as metastatic breast and lung cancer, as few as 8% of patients with advanced cancer qualify for targeted oncology medications, and even fewer benefit. Other limitations include serious adverse events, illustrated by a 20% to 30% rate of heart attack, stroke, or peripheral vascular events among patients taking ponatinib, which is used in treating chronic myelogenous leukemia. Immune checkpoint inhibitor therapy-related adverse effects such as hypothyroidism are common, and more severe adverse events such as colitis and pneumonitis can be fatal and require immediate intervention. Drug interactions with widely prescribed medications such as antacids and warfarin are common. Additionally, financial toxicities are a problem for patients with cancer who are using costly targeted therapies. Future directions for targeted oncology include tumor-agnostic drugs, which target a given mutation and could be used in treating cancers from multiple organ types. An overview of indications, mechanism of action, and toxicities of targeted cancer therapies is offered here.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Curriculum; Education, Medical, Continuing; Female; Humans; Male; Middle Aged; Molecular Targeted Therapy; Neoplasms; United States
PubMed: 33507053
DOI: No ID Found -
Radiation Oncology (London, England) Apr 2016Here we evaluate the current status of clinical research on regional hyperthermia (RHT) in combination with chemotherapy or radiation therapy in paediatric oncology.Data... (Review)
Review
Here we evaluate the current status of clinical research on regional hyperthermia (RHT) in combination with chemotherapy or radiation therapy in paediatric oncology.Data were identified in searches of MEDLINE, Current Contents, PubMed, and references from relevant articles using medical subject headings including hyperthermia, cancer, paediatric oncology, children, radiation therapy and chemotherapy. Currently, only two RHT centres exist in Europe which treat children. Clinical RHT research in paediatric oncology has as yet been limited to children with sarcomas and germ cell tumours that respond poorly to or recur after chemotherapy. RHT is a safe and effective treatment delivering local thermic effects, which may also stimulate immunological processes via heat-shock protein reactions. RHT is used chiefly in children and adolescents with sarcomas or germ cell tumours located in the abdomino-pelvic region, chest wall or extremities to improve operability or render the tumour operable. It could potentially be combined with radiation therapy in a post-operative R1 setting where more radical surgery is not possible or combined with chemotherapy instead of radiation therapy in cases where the necessary radiation dose is impossible to achieve or would have mutilating consequences. RHT might also be an option for chemotherapy intensification in the neoadjuvant first-line treatment setting for children and adolescents, as was recently reflected in the promising long-term outcome data in adults with high-risk soft tissue sarcomas (EORTC 62961/ESHO trial).The limited data available indicate that combining RHT with chemotherapy is a promising option to treat germ cell tumours and, potentially, sarcomas. RHT may also be beneficial in first-line therapy in children, adolescents and young adults. The research should focus on optimising necessary technical demands and then initiate several clinical trials incorporating RHT into interdisciplinary treatment of children, adolescents and young adults that include translational research components exploring potential immunological mechanisms of action.
Topics: Adolescent; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Body Weight; Child; Combined Modality Therapy; Drug Therapy; Fever; Fibroma; Humans; Hyperthermia, Induced; Medical Oncology; Neoplasm Recurrence, Local; Neoplasms; Pediatrics; Radiotherapy; Sarcoma; Young Adult
PubMed: 27138749
DOI: 10.1186/s13014-016-0639-1 -
The American Journal of Tropical... Sep 2013Melioidosis is an important cause of morbidity and mortality in northern Australia and Southeast Asia. Diagnosis is best made by isolation of Burkholderia pseudomallei...
Melioidosis is an important cause of morbidity and mortality in northern Australia and Southeast Asia. Diagnosis is best made by isolation of Burkholderia pseudomallei from clinical specimens. A variety of clinical presentations are described, including neurologic disease. The aim of this study was to review admissions with confirmed neurologic melioidosis to a regional hospital in a region to which melioidosis is endemic during 1995-2011. There were 12 culture-confirmed cases of neurologic melioidosis, of which two were detected by analysis of cerebrospinal fluid. Four of these cases were in children. Significant clinical features were fever, headache, and ataxia. Common changes on magnetic resonance imaging T2-weighted scans included ring-enhancing lesions and leptomeningeal enhancement. There were four deaths and an additional four patients had significant long-term neurologic sequelae. When considering the etiology of undifferentiated neurologic disease, an awareness of the possibility of neurologic melioidosis is important in disease-endemic regions.
Topics: Administration, Intravenous; Adolescent; Adult; Aged; Anti-Bacterial Agents; Asia, Southeastern; Australia; Burkholderia pseudomallei; Cerebrospinal Fluid; Child; Child, Preschool; Endemic Diseases; Hospitalization; Humans; Magnetic Resonance Imaging; Melioidosis; Middle Aged; Nervous System Diseases; Risk Factors; Specimen Handling; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography; Young Adult
PubMed: 23836574
DOI: 10.4269/ajtmh.12-0559 -
BMJ (Clinical Research Ed.) Feb 2005
Topics: Drug Design; Drug Industry; Drug Therapy; Europe; Global Health; Humans; Public Health; Rare Diseases; World Health Organization
PubMed: 15718518
DOI: 10.1136/bmj.330.7488.376 -
Pharmacology & Therapeutics 1983Recent developments have made regional chemotherapy a more rational endeavour. The important pharmacokinetic principles have been defined. The increase in regional... (Review)
Review
Recent developments have made regional chemotherapy a more rational endeavour. The important pharmacokinetic principles have been defined. The increase in regional exposure achieved is a direct function of a drug's total body clearance and is an inverse function of the permeability-area product (defining ease of egress) for third spaces or of the regional arterial blood flow for intraarterial infusion. Agents having appropriate properties are available. For new agents with appropriate pharmacokinetic parameters, regional chemotherapy may provide a means to examine the dose response against measurable tumors in the regions in question. The observation that most tumors are hypervascular may be crucial to the development of selective treatments using microspheres to deliver therapy in direct proportion to the density of the microvasculature. Regionally infused vasoconstrictors (epinephrine, angiotensin) may allow shunting of flow away from normal tissue toward tumor without potentially serious systemic cardiovascular effects. Investigations and applications of regional chemotherapy have been fostered immensely by the reliably and convenience of the Infusaid implantable pump and by implantable injection ports. The problem of systemic failure with regional approaches still remains but is approachable using pharmacologically rational programs aimed at delivering maximal systemic chemotherapy along with regional treatment. In hepatic arterial therapy, in particular, a randomized prospective study is being considered to examine the impact of such combined treatment versus regional therapy alone and versus systemic chemotherapy alone for metastatic colorectal cancer to liver. Thus, the future for regional chemotherapy appears exciting. There are many opportunities to apply therapeutic principles rationally with the potential of significant benefit to many patients.
Topics: Animals; Antineoplastic Agents; Chemotherapy, Cancer, Regional Perfusion; Humans; Infusions, Intra-Arterial; Injections, Intraperitoneal; Kinetics; Models, Biological; Neoplasms; Regional Blood Flow
PubMed: 6353444
DOI: 10.1016/0163-7258(83)90077-3 -
Future Oncology (London, England) Apr 2022The aim of this systematic literature review was to describe treatment patterns in nonmetastatic non-small-cell lung cancer. A search was conducted in MEDLINE and... (Review)
Review
The aim of this systematic literature review was to describe treatment patterns in nonmetastatic non-small-cell lung cancer. A search was conducted in MEDLINE and EMBASE. Eligible studies were multicentered (>50 patients) and conducted after 2000 in North America, Europe and Asia. Twenty studies met the eligibility criteria. Based on US and Canadian studies in the resectable population, the proportion of patients who received neoadjuvant chemotherapy/chemoradiotherapy and adjuvant chemotherapy/chemoradiotherapy increased with increasing stage (i.e., from <3% in stage I to about 40% in stage III and from 15% in stage I to 30% in stage III, respectively). Within the resectable population, the breakdown between bimodal and trimodal therapy was variable, suggesting that clinical practice is not uniform. Overall, studies were heterogeneous, precluding data extrapolation across regions. Despite heterogeneity and limited evidence, this review suggested an increase in neoadjuvant and adjuvant chemotherapy with increasing stage, generally in line with treatment guidelines.
Topics: Canada; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Humans; Lung Neoplasms; Neoadjuvant Therapy; Neoplasm Staging
PubMed: 35073732
DOI: 10.2217/fon-2021-1417 -
Journal of Thoracic Oncology : Official... Jun 2007Cancer of the esophagus continues to be a threat to public health. The common practice is esophagectomy for surgically resectable tumors and radiochemotherapy for... (Review)
Review
Cancer of the esophagus continues to be a threat to public health. The common practice is esophagectomy for surgically resectable tumors and radiochemotherapy for locally advanced, unresectable tumors. However, local regional tumor control and overall survival of esophageal cancer patients after the standard therapies remain poor, approximately 30% of patients treated with surgery only will develop local recurrence, and 50% to 60% patients treated with radiochemotherapy only fail local regionally due to persistent disease or local recurrence. Esophagectomy after radiochemotherapy or preoperative radiochemotherapy has increased the complete surgical resection rate and local regional control without a significant survival benefit. Induction chemotherapy followed by preoperative radiochemotherapy has produced encouraging results. In addition to patient-, tumor-, and treatment-related factors, involvement of celiac axis nodes, number of positive lymph nodes after preoperative radiochemotherapy, incomplete pathologic response, high metabolic activity on positron emission tomography scan after radiochemotherapy, and incomplete surgical resection are factors associated with a poor outcome. Radiochemotherapy followed by surgery is associated with significant adverse effects, including treatment-related pneumonitis, postoperative pulmonary complications, esophagitis and pericarditis. The incidence and severity of the adverse effects are associated with chemotherapy and radiotherapy dosimetric factors. Innovative treatment strategies including physically and biologically molecular targeted therapy is needed to improve the treatment outcome of patients with esophageal cancer.
Topics: Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Combined Modality Therapy; Esophageal Neoplasms; Humans
PubMed: 17545853
DOI: 10.1097/01.JTO.0000275339.62831.5e -
The Journal of Medical Investigation :... 2022Chemotherapy for cancer has significantly improved owing to the increasing number of effective chemotherapeutic agents and supportive care. Recently, the number of older... (Review)
Review
Chemotherapy for cancer has significantly improved owing to the increasing number of effective chemotherapeutic agents and supportive care. Recently, the number of older cancer patients has rapidly increased owing to the aging of the global population. However, in most cases, it is difficult to treat those using similar dosages or schedules as that of younger patients because older patients generally have unfavorable factors, such as decreased performance status and physical and cognitive conditions, thus increasing the incidence of complications and side effects. Chemotherapy for gastrointestinal cancers has made significant progress in recent years with the introduction of molecular-targeted agents and immunotherapy. However, clinical trials showed limited evidence regarding the efficacy of chemotherapy in older cancer patients, accounting for half of all patients, making it difficult to develop a well-established treatment strategy. This review aimed to evaluate the current state of chemotherapy for gastrointestinal cancer in older adults. Furthermore, the limitations and future perspectives were discussed. J. Med. Invest. 69 : 25-30, February, 2022.
Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Gastrointestinal Neoplasms; Humans; Japan
PubMed: 35466142
DOI: 10.2152/jmi.69.25 -
Asian Pacific Journal of Cancer... 2015Incidence rates of nasopharyngeal carcinoma are high in Indonesia, Singapore and South-Eastern China. Chemoradiotherapy has been the standard regimen for locally... (Review)
Review
Incidence rates of nasopharyngeal carcinoma are high in Indonesia, Singapore and South-Eastern China. Chemoradiotherapy has been the standard regimen for locally advanced nasopharyngeal carcinoma according to guidelines from the National Comprehensive Cancer Network. Recently, advances in the management of nasopharyngeal carcinoma have transferred into better treatment outcomes. Most phase III clinical trials support the addition of concurrent chemotherapy to radiotherapy for the initial treatment of these patients. Studies evaluating effects and toxicity of concurrent chemotherapy with different regimens have been reported. However, the status of adding adjuvant chemotherapy or induction chemotherapy remains controversial. Recent studies have shown that adjuvant chemotherapy with two or three cycles may improve survival for nasopharyngeal carcinoma with stage N2-3 disease or with persistently detectable plasma EBV DNA after radiotherapy. This review examines the pertinent issues and latest studies concerning the management of loco-regionally advanced NPC, regarding concurrent chemotherapy, adjuvant chemotherapy, and induction chemotherapy in decades.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Prognosis; Remission Induction
PubMed: 26163598
DOI: 10.7314/apjcp.2015.16.12.4825