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Genes May 2022"The story of cancer is the story of human ingenuity, resilience, and perseverance, but also of hubris, paternalism, and misperception" (Siddhartha Mukherjee). The... (Review)
Review
"The story of cancer is the story of human ingenuity, resilience, and perseverance, but also of hubris, paternalism, and misperception" (Siddhartha Mukherjee). The present review discusses the evolution of early breast cancer (BC) treatment philosophy in the last 50 years and the shift from an emphasis on local therapy to an emphasis on systemic precision treatment options.
Topics: Breast Neoplasms; Female; Humans; Immunotherapy
PubMed: 35741721
DOI: 10.3390/genes13060960 -
Cancer Cell Mar 2023The tumor microenvironment (TME) is composed of many different cellular and acellular components that together drive tumor growth, invasion, metastasis, and response to... (Review)
Review
The tumor microenvironment (TME) is composed of many different cellular and acellular components that together drive tumor growth, invasion, metastasis, and response to therapies. Increasing realization of the significance of the TME in cancer biology has shifted cancer research from a cancer-centric model to one that considers the TME as a whole. Recent technological advancements in spatial profiling methodologies provide a systematic view and illuminate the physical localization of the components of the TME. In this review, we provide an overview of major spatial profiling technologies. We present the types of information that can be extracted from these data and describe their applications, findings and challenges in cancer research. Finally, we provide a future perspective of how spatial profiling could be integrated into cancer research to improve patient diagnosis, prognosis, stratification to treatment and development of novel therapeutics.
Topics: Humans; Tumor Microenvironment; Neoplasms; Prognosis; Immunotherapy
PubMed: 36800999
DOI: 10.1016/j.ccell.2023.01.010 -
Frontiers in Immunology 2022Despite advances in treatment for multiple myeloma, the majority of patients ultimately develop relapsed disease marked by immune evasion and resistance to standard... (Review)
Review
Despite advances in treatment for multiple myeloma, the majority of patients ultimately develop relapsed disease marked by immune evasion and resistance to standard therapy. Immunotherapy has emerged as a powerful tool for tumor-directed cytotoxicity with the unique potential to induce immune memory to reduce the risk of relapse. Understanding the specific mechanisms of immune dysregulation and dysfunction in advanced myeloma is critical to the development of further therapies that produce a durable response. Adoptive cellular therapy, most strikingly CAR T cell therapy, has demonstrated dramatic responses in the setting of refractory disease. Understanding the factors that contribute to immune evasion and the mechanisms of response and resistance to therapy will be critical to developing the next generation of adoptive cellular therapies, informing novel combination therapy, and determining the optimal time to incorporate immune therapy in the treatment of myeloma.
Topics: Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Immunotherapy; Immunotherapy, Adoptive; Combined Modality Therapy
PubMed: 36389674
DOI: 10.3389/fimmu.2022.1027385 -
Theranostics 2020The current achievements in treating glioblastoma (GBM) patients are not sufficient because many challenges exist, such as tumor heterogeneity, the blood brain barrier,... (Review)
Review
The current achievements in treating glioblastoma (GBM) patients are not sufficient because many challenges exist, such as tumor heterogeneity, the blood brain barrier, glioma stem cells, drug efflux pumps and DNA damage repair mechanisms. Drug combination therapies have shown increasing benefits against those challenges. With the help of nanocarriers, enhancement of the efficacy and safety could be gained using synergistic combinations of different therapeutic agents. In this review, we will discuss the major issues for GBM treatment, the rationales of drug combinations with or without nanocarriers and the principle of enhanced permeability and retention effect involved in nanomedicine-based tumor targeting and promising nanodiagnostics or -therapeutics. We will also summarize the recent progress and discuss the clinical perspectives of nanocarrier-based combination therapies. The goal of this article was to provide better understanding and key considerations to develop new nanomedicine combinations and nanotheranostics options to fight against GBM.
Topics: Animals; Antineoplastic Agents; Blood-Brain Barrier; Brain Neoplasms; Combined Modality Therapy; Drug Carriers; Drug Therapy, Combination; Glioblastoma; Humans; Nanoparticles; Permeability; Theranostic Nanomedicine
PubMed: 31938069
DOI: 10.7150/thno.38147 -
Current Oncology (Toronto, Ont.) Feb 2020Soft-tissue sarcoma (sts) is a rare mesenchymal malignancy that accounts for less than 1% of all adult tumours. Despite the successful advancement of localized therapies... (Review)
Review
Soft-tissue sarcoma (sts) is a rare mesenchymal malignancy that accounts for less than 1% of all adult tumours. Despite the successful advancement of localized therapies such as surgery and radiotherapy, these tumours can, for many, recur-often with metastatic disease. In the advanced setting, the role of systemic therapies is modest and is associated with poor survival. With the discovery of immunotherapies in other tumour types such as melanoma and lung cancer, interest has been renewed in exploring immunotherapy in sts. The biology of some stss makes them ripe for immunotherapy intervention; for example, some stss might have chromosomal translocations resulting in pathognomonic fusion products that have been shown to express cancer/testis antigens. Here, we present a targeted review of the published data and ongoing clinical trials for immunotherapies in patients with sarcoma, which comprise immune checkpoint inhibitors, adoptive cell therapies, and cancer vaccines.
Topics: Humans; Immunotherapy; Sarcoma; Soft Tissue Neoplasms
PubMed: 32174754
DOI: 10.3747/co.27.5407 -
Breast (Edinburgh, Scotland) Mar 2022Locally advanced breast cancer (LABC) is defined here as inoperable breast adenocarcinoma without distant metastases. Patients with LABC require a multidisciplinary...
Locally advanced breast cancer (LABC) is defined here as inoperable breast adenocarcinoma without distant metastases. Patients with LABC require a multidisciplinary approach. Given the risk of distant metastasis, staging exams are necessary. The incidence of LABC (stages IIIB and IIIC) has decreased in recent years. LABC has rarely been investigated separately: patients with LABC have participated both in clinical trials of palliative and of neoadjuvant therapy. Most trials did not analyze responses and long-term outcomes independently; thus, the treatment of patients with LABC is extrapolated from studies of patients with less or more advanced disease. Pathologic confirmation and molecular profiling are essential for the choice of neoadjuvant chemotherapy. Preoperative endocrine therapy may be considered in certain clinical situations; the addition of a CDK4/6 inhibitor is being investigated. HER2 positive LABCs are targeted with anti-HER2 agents combined with chemotherapy. PD-1 and PD-L1 antibodies in 'triple-negative' LABC are promising. Excellent responses to neoadjuvant therapy enable conservative surgery in many patients; however, inflammatory breast cancer may still indicate mastectomy. Postoperative radiotherapy is usually indicated. Target volumes include breast/chest wall, axillary, supraclavicular and internal mammary nodal basins. Preoperative radiation therapy can be useful in patients without response to systemic therapies. Palliative surgery for poor responders after neoadjuvant systemic and radiation therapy can be considered. Multidisciplinary teams can optimize local control and prevent relapses. However, modest improvement in survival was achieved between 2000 and 2014 underscoring the unmet need in patients with LABC who will benefit from specific research efforts in this disease entity.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Humans; Mastectomy; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Triple Negative Breast Neoplasms
PubMed: 34930650
DOI: 10.1016/j.breast.2021.12.011 -
F1000Research 2018Brain metastases are the most common malignancy encountered in the central nervous system (CNS), with up to 30-40% of cancer patients developing brain metastases at some... (Review)
Review
Brain metastases are the most common malignancy encountered in the central nervous system (CNS), with up to 30-40% of cancer patients developing brain metastases at some point during the course of their disease. The management of brain metastasis is rapidly evolving and the roles of local therapies such as whole-brain radiation therapy, stereotactic radiosurgery, and resection along with systemic therapies are in flux. An emphasis on the neurocognitive side effects associated with treatment has gained prominence. Novel molecular studies have demonstrated important evolutionary patterns underpinning the development of brain metastasis and leptomeningeal disease, which may be key to unlocking new therapeutic strategies. This article provides a framework for incorporating the results of recent randomized radiotherapy clinical trials into practice, expounds upon the emphasis on cognition being an important driver in therapeutic selection, describes the importance of CNS-penetrating systemic therapies, and provides an overview of the novel molecular insights that will likely set the stage for future developments in this field.
Topics: Brain Neoplasms; Disease Management; Humans; Neoplasm Metastasis; Radiosurgery; Radiotherapy; Therapeutics
PubMed: 30473769
DOI: 10.12688/f1000research.15903.1 -
International Braz J Urol : Official... 2020Standard management of muscle-invasive bladder cancer involves radical cystectomy with pelvic lymph node dissection. However, patients may be ineligible for surgery or... (Review)
Review
BACKGROUND
Standard management of muscle-invasive bladder cancer involves radical cystectomy with pelvic lymph node dissection. However, patients may be ineligible for surgery or may wish to avoid the morbidity of cystectomy due to quality of life concerns. Bladder preservation therapies have emerged as alternatives treatment options that can provide comparable oncologic outcomes while maintaining patients' quality of life.
OBJECTIVE
To review bladder preservation therapies, patient selection criteria, and functional and oncologic outcomes for BPT in muscle-invasive bladder cancer.
MATERIALS AND METHODS
We conducted a comprehensive literature review of bladder preservation therapies in Pubmed and Embase.
DISCUSSION
The ideal patient for BPT has low-volume T2 disease, absence of CIS, absence of hydronephrosis, and a maximal TURBT with regular surveillance. Technological advancements involving cancer staging, TURBT technique, and chemotherapy and radiation therapy regimens have improved BPT outcomes, with oncologic outcomes now comparable to those of radical cystectomy. Advancements in BPT also includes a heightened focus on improving quality of life for patients undergoing bladder preservation. Preservation strategies with most evidence for use include trimodality therapy and partial cystectomy with pelvic lymph node dissection.
CONCLUSIONS
This review highlights the breadth of strategies that aim to preserve a patient's bladder while still optimizing local tumor control and overall survival. Future areas for innovation include the use of predictive biomarkers and implementation of immunotherapy, moving the field towards patient-tailored care.
Topics: Combined Modality Therapy; Cystectomy; Humans; Neoplasm Invasiveness; Neoplasm Staging; Organ Sparing Treatments; Urinary Bladder Neoplasms
PubMed: 31961624
DOI: 10.1590/S1677-5538.IBJU.2020.99.01 -
Modern Pathology : An Official Journal... Jan 2018Nonsurgical treatments for prostate cancer include androgen-deprivation therapy (ADT), radiation therapy (RT), ablative therapies, chemotherapy, and newly emerging... (Review)
Review
Nonsurgical treatments for prostate cancer include androgen-deprivation therapy (ADT), radiation therapy (RT), ablative therapies, chemotherapy, and newly emerging immunotherapies. These approaches can be used alone or in combination depending on the clinical scenario. ADT is typically reserved for high-risk locally or systemically advanced disease that is not amenable to curative surgery. Radiation therapy can be used instead of surgery as primary therapy with curative intent for low-intermediate-risk disease as well as for control of locally advanced disease not suitable for surgery. Ablative therapies can be used as primary therapy for low-intermediate-risk disease or as salvage therapy for clinically localized disease where RT has failed. Chemotherapy and immune-based therapies are currently used for androgen-independent disease, although the indications for these approaches may well change as new data from clinical trials accrue. Pathologists should be able to recognize tissue changes associated with these treatments to provide information that will optimize patient management. This is particularly true in situations where clinical history of recent or remote nonsurgical treatment is not provided with the specimen. In the absence of this information, pathologists encountering the features described herein are encouraged to review patient records or communicate directly with clinical colleagues to determine how a given patient was treated and when.
Topics: Androgen Antagonists; Cryotherapy; Dietary Supplements; Drug Therapy; Extracorporeal Shockwave Therapy; Humans; Immunotherapy; Laser Therapy; Male; Neoplasm Grading; Photochemotherapy; Prostatic Neoplasms; Treatment Outcome
PubMed: 29297495
DOI: 10.1038/modpathol.2017.158 -
CA: a Cancer Journal For Clinicians Sep 2019Brachytherapy is a specific form of radiotherapy consisting of the precise placement of radioactive sources directly into or next to the tumor. This technique is... (Review)
Review
Brachytherapy is a specific form of radiotherapy consisting of the precise placement of radioactive sources directly into or next to the tumor. This technique is indicated for patients affected by various types of cancers. It is an optimal tool for delivering very high doses to the tumor focally while minimizing the probability of normal tissue complications. Physicians from a wide range of specialties may be involved in either the referral to or the placement of brachytherapy. Many patients require brachytherapy as either primary treatment or as part of their oncologic care. On the basis of high-level evidence from randomized controlled trials, brachytherapy is mainly indicated: 1) as standard in combination with chemoradiation in patients with locally advanced cervical cancer; 2) in surgically treated patients with uterine endometrial cancer for decreasing the risk of vaginal vault recurrence; 3) in patients with high-risk prostate cancer to perform dose escalation and improve progression-free survival; and 4) in patients with breast cancer as adjuvant, accelerated partial breast irradiation or to boost the tumor bed. In this review, the authors discuss the clinical relevance of brachytherapy with a focus on indications, levels of evidence, and results in the overall context of radiation use for patients with cancer.
Topics: Antineoplastic Agents; Brachytherapy; Chemoradiotherapy; Disease Progression; Dose Fractionation, Radiation; Education, Medical, Continuing; Evidence-Based Medicine; Humans; Neoadjuvant Therapy; Neoplasms; Patient Selection; Physicians; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 31361333
DOI: 10.3322/caac.21578