7 Treatment strategies during targeted therapy

2014 ◽  
Vol 18 ◽  
pp. S2
Author(s):  
C.B. Boers-Doets
Keyword(s):  
Targeted Therapy ◽  
Treatment Strategies

scholarly journals KRAS-Mutant Non–Small Cell Lung Cancer: Recent Progress

2021 ◽  
Author(s):  
chun shu ◽  
Yuling Liu ◽  
chunlu Zhou
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Kras Mutation ◽  
Recent Progress ◽  
Treatment Strategies ◽  
Small Cell ◽  
Treatment Model ◽  
Small Cell Lung ◽  
Mutant Population

The KRAS mutant population has been undruggable for 40 years. G12C inhibitors and immunotherapy are the beginning of success. It is necessary to summarize the successful experience of the existing treatment model and explore the direction of the next treatment. In this review, we discuss the latest developments in targeted therapy and immunotherapy for KRAS-mutation NSCLC, aiming to provide direction or enlightenment for future treatment strategies.

Evolving Systemic Treatment Landscape for Patients With Advanced Renal Cell Carcinoma

2018 ◽  
Vol 36 (36) ◽  
pp. 3615-3623 ◽  
Author(s):  
Rana R. McKay ◽  
Dominick Bossé ◽  
Toni K. Choueiri
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Systemic Treatment ◽  
Traditional Approach ◽  
Performance Status ◽  
Treatment Strategies ◽  
Advanced Renal Cell Carcinoma ◽  
Treatment Paradigm

Purpose To outline current practices and challenges in the systemic management of patients with advanced renal cell carcinoma (RCC). Design We conducted a focused review of hallmark randomized controlled trials informing the systemic treatment of patients with RCC. We concentrated on trials informing the use of combination therapies, therapy in both treatment-naïve and previously treated patients, sequential treatment strategies, and schedules. Results The systemic treatment of advanced RCC has experienced tremendous progress over the past 15 years. An improved understanding of the canonical pathways implicated in RCC pathogenesis has resulted in the development of molecularly targeted and immunotherapy options for patients. These therapies have replaced cytokine-based treatments as the standard of care for patients with advanced RCC. Until recently, sequential vascular endothelial growth factor (VEGF)–targeted therapy or VEGF-targeted therapy followed by mammalian target of rapamycin inhibition has been the prevailing treatment paradigm for patients. However, newer agents such as cabozantinib and nivolumab have challenged this traditional approach. In addition, combination treatments including nivolumab plus ipilimumab and atezolizumab plus bevacizumab have transformed the RCC treatment landscape, and other doublet combinations in clinical testing will likely continue to alter the treatment paradigm in RCC. Currently, factors that inform treatment selection between different therapy options include performance status, comorbidities, prognostic risk stratification, treatment adverse event profile, and mode of administration, with no Level I evidence for predictive biomarker use in clinic. Conclusions The treatment options for advanced RCC are rapidly evolving since the introduction of VEGF-targeted therapy, immunotherapy with checkpoint blockade and, more recently, combination regimens. Despite the success of these regimens, advanced RCC remains a largely incurable disease, and additional strategies are warranted.

scholarly journals Targeted therapy of gastroenteropancreatic neuroendocrine tumours: preclinical strategies and future targets

2018 ◽  
Vol 7 (1) ◽  
pp. R1-R25 ◽  
Author(s):  
E T Aristizabal Prada ◽  
C J Auernhammer
Keyword(s):  
Targeted Therapy ◽  
Molecular Targeted Therapy ◽  
Histone Deacetylase Inhibitors ◽  
Neuroendocrine Tumours ◽  
Objective Response ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Beta Catenin ◽  
Cell Cycle Regulators ◽  
Preclinical Research

Molecular targeted therapy of advanced neuroendocrine tumours (NETs) of the gastroenteropancreatic (GEP) system currently encompasses approved therapy with the mammalian target of rapamycin (mTOR) inhibitor everolimus and the multi-tyrosinkinase inhibitor sunitinib. However, clinical efficacy of these treatment strategies is limited by low objective response rates and limited progression-free survival due to tumour resistance. Further novel strategies for molecular targeted therapy of NETs of the GEP system are needed. This paper reviews preclinical research models and signalling pathways in NETs of the GEP system. Preclinical and early clinical data on putative novel targets for molecular targeted therapy of NETs of the GEP system are discussed, including PI3K, Akt, mTORC1/mTORC2, GSK3, c-Met, Ras–Raf–MEK–ERK, embryogenic pathways (Hedgehog, Notch, Wnt/beta-catenin, TGF-beta signalling and SMAD proteins), tumour suppressors and cell cycle regulators (p53, cyclin-dependent kinases (CDKs) CDK4/6, CDK inhibitor p27, retinoblastoma protein (Rb)), heat shock protein HSP90, Aurora kinase, Src kinase family, focal adhesion kinase and epigenetic modulation by histone deacetylase inhibitors.

scholarly journals Dissecting targeted therapy resistance: Integrating models to quantify environment mediated drug resistance

2017 ◽  
Author(s):  
Noemi Picco ◽  
Erik Sahai ◽  
Philip K. Maini ◽  
Alexander R. A. Anderson
Keyword(s):  
Drug Resistance ◽  
Targeted Therapy ◽  
Targeted Therapies ◽  
Carrying Capacity ◽  
Conflicts Of Interest ◽  
Treatment Strategies ◽  
Model Systems ◽  
Significant Heterogeneity

AbstractDrug resistance is the single most important driver of cancer treatment failure for modern targeted therapies. This resistance may be due to the presence of dormant or aggressive tumor cell phenotypes or to context-driven protection. Non-malignant cells and other factors, constituting the microenvironment in which the tumor grows (the stroma), are now thought to play a crucial role in both therapeutic response and resistance. Specifically, the dialogue between the tumor and stroma has been shown to modulate the response to molecularly targeted therapies, through proliferative and survival signaling. The goal of this work is to investigate interactions between a growing tumor and its surrounding stroma in facilitating the emergence of drug resistance. We use mathematical modeling as a theoretical framework to bridge between experimental models and scales, with the aim of separating the intrinsic and extrinsic components of resistance in BRAF mutated melanoma. The model describes tumor-stroma dynamics both with and without treatment. Calibration of our model, through the integration of experimental data, revealed significant variation across animal replicates in either the intensity of stromal promotion or intrinsic tissue carrying capacity. Furthermore our study highlights the need to account for this variation in the design of treatment strategies. Major Findings. Through the integration of a simple mathematical model with in vitro and in vivo experimental growth dynamics of melanoma cell lines (both with and without drug), we were able to dissect the relative contributions of intrinsic versus environmental resistance. Our study revealed significant heterogeneity in vivo, indicating that there is a diversity of either stromal promotion or tumor carrying capacity under targeted therapy. We believe this variation may be one possible explanation for the heterogeneity observed across patients and within individual patients with multiple metastases. Therefore, quantifying this variation both within in vivo model systems and in individual patients could have a significant impact on the design of future treatment strategies that target both the tumor and stroma. Further, we present guidelines for building more effective and longer lasting therapeutic strategies utilizing our experimentally calibrated model. These strategies explicitly consider the protective nature of the stroma and utilize inhibitors that modulate it.PrecisQuantification of the environmental contribution to drug resistance reveals heterogeneity that significantly alters treatment dynamics that can be exploited for therapeutic gain.Financial SupportPicco and Anderson: US National Cancer Institute grant U01CA151924.Picco: UK Engineering and Physical Sciences Research Council (EPSRC grant number EP/G037280/1).Conflict of Interest DisclosureThe authors declare no potential conflicts of interest.

scholarly journals De-differentiation in thyroid cancer- an increasingly appreciated concept

2021 ◽  
Vol 8 (2) ◽  
pp. 757
Author(s):  
Prasanth Poolakkil ◽  
Sajith Babu Thavarool ◽  
Satheesan Balasubramanyam ◽  
Kandathil Joseph Philip
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapy ◽  
Rare Case ◽  
Treatment Strategies ◽  
Good Prognosis ◽  
Genetic Changes ◽  
Molecular Changes ◽  
Clinical Behaviour ◽  
Differentiation Theory ◽  
Differentiation Pattern

Thyroid cancer is the most common endocrine malignancy. In general, they are said to be of good prognosis, still there are a few aggressive variants. Differentiated carcinomas like papillary and follicular comprise of major proportion and have a less aggressive clinical behaviour, even though some of them tend to be otherwise. De-differentiated and undifferentiated cancers are more aggressive. There has been an already existing theory that these de-differentiated cancers arise from differentiated ones by a process of stepwise molecular changes. There are already reported cases of coexistence of multiple histologies. Appreciation of dedifferentiation and identification of the genetic changes may be of help in forming improved treatment strategies, including targeted therapy. This article is to report a rare case we came across, in which three different histologies coexisted and may be pointing towards graded de-differentiation pattern. This is a further support to the stepwise de-differentiation theory.

scholarly journals Is There a Role for Neoadjuvant Targeted Therapy to Downsize Primary Tumors for Organ Sparing Strategies in Renal Cell Carcinoma?

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
A. Bex ◽  
B. K. Kroon ◽  
R. de Bruijn
Keyword(s):  
Renal Function ◽  
Targeted Therapy ◽  
Treatment Strategies ◽  
Clinical Problem ◽  
Current Evidence ◽  
Small Renal Masses ◽  
Renal Masses ◽  
Primary Tumors ◽  
Risk Of Death ◽  
Nephron Sparing

With an increasing number of small renal masses being diagnosed organ-preserving treatment strategies such as nephron-sparing surgery (NSS) or radiofrequency and cryoablation are gaining importance. There is evidence that preserving renal function reduces the risk of death of any cause, cardiovascular events, and hospitalization. Some patients have unfavourable tumor locations or large tumors unsuitable for NSS or ablation which is a clinical problem especially in those with imperative indications to preserve renal function. These patients may benefit from downsizing primary tumors by targeted therapy. This paper provides an overview of the current evidence, safety, controversies, and ongoing trials.

Targeted therapies and checkpoint inhibitors in sarcoma

QJM ◽  
2021 ◽  
Author(s):  
M Vasella ◽  
E Gousopoulos ◽  
M Guidi ◽  
G Storti ◽  
S Y Song ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Suppressor Gene ◽  
Treatment Practice ◽  
Therapeutic Concepts

Abstract Sarcomas are defined as a group of mesenchymal malignancies with over 100 heterogeneous subtypes. As a rare and difficult to diagnose entity, micrometastasis is already present at the time of diagnosis in many cases. Current treatment practice of sarcomas consists mainly of surgery, (neo)adjuvant chemo- and/or radiotherapy. Although the past decade has shown that particular genetic abnormalities can promote the development of sarcomas, such as translocations, gain-of-function mutations, amplifications or tumor suppressor gene losses, these insights have not led to established alternative treatment strategies so far. Novel therapeutic concepts with immunotherapy at its forefront have experienced some remarkable success in different solid tumors while their impact in sarcoma remains limited. In this review, the most common immunotherapy strategies in sarcomas, such as immune checkpoint inhibitors, targeted therapy and cytokine therapy are concisely discussed. The programmed cell death (PD)-1/PD-1L axis and apoptosis-inducing cytokines, such as TNF-related apoptosis-inducing ligand (TRAIL), have not yielded the same success like in other solid tumors. However, in certain sarcoma subtypes, e.g. liposarcoma or undifferentiated pleomorphic sarcoma, encouraging results in some cases when employing immune checkpoint inhibitors in combination with other treatment options were found. Moreover, newer strategies such as the targeted therapy against the ancient cytokine macrophage migration inhibitory factor (MIF) may represent an interesting approach worth investigation in the future.

scholarly journals A Concise Review on Targeted Therapy for Oral Cancer

2020 ◽  
Vol 11 (SPL3) ◽  
pp. 84-90
Author(s):  
Thariny E ◽  
Ezhilarasan D ◽  
Brundha M P
Keyword(s):  
Targeted Therapy ◽  
Oral Cancer ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Surgical Removal ◽  
Oral Cancers ◽  
Concise Review ◽  
Growth Prognosis ◽  
Intrinsic Drug Resistance

Oral Cancer has become a center of attraction in the world, causing health problems. Carcinoma that involves the lip, tongue, mouth surface, palate, and throat is also serious if not diagnosed and treated. Current treatment strategies involve surgical removal, using chemotherapeutic drugs and radiation therapy. The event of targeted therapy aid in medicine together with oral cancers is that the basic dependence of neoplasm cells on biological pathways which might be coupled to medicine that inhibit those pathways. The resistance of tumor cells to anticancer drugs is a known method which is investigated experimentally at the molecular level. Immunotherapeutic agent resistance is thought to affect the efficacy of anticancer remedies. The induced or intrinsic drug resistance has a strong effect on the survival and cancer growth prognosis by suppression of cancer-associated cell signaling pathways of cancer patients. Targeted therapy also has a significant inhibitory ability, thus demonstrating the high quality of treatment. Hence this concise review discusses the implementation of molecular targeted therapy in the treatment of oral cancer.

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