Potent ros1 inhibitor. Medical search. Frequent questions

Recently, the small molecule tyrosine kinase inhibitor, crizotinib, was approved for the treatment of patients with metastatic NSCLC whose tumors are ROS1 -positive. (wikipedia.org)
Entrectinib is a novel tyrosine kinase inhibitor (TKI) with activity against ROS1 and NTRK fusions that has been approved by the US Food and Drug Administration. (medscape.com)
Objective: We aim to summarize recent studies related to the synthesis, mechanism of action, and clinical trials of the newly approved selective tyrosine kinase inhibitor entrectinib. (currentmedicinalchemistry.com)
Epidermal growth factor receptor, a well-known biomarker for targeted therapy at present, was first brought up with potential clinical responsiveness to tyrosine kinase inhibitor gefitinib in 2004[ 6 ]. (biomedcentral.com)
Recently, results from the phase I/II TRIDENT-1 clinical trial suggest that a novel tyrosine kinase inhibitor (TKI), repotrectinib, shows antitumor activity in ROS-1-positive advanced non-small cell lung cancer patients, including those previously treated with other ROS-1 inhibitors. (lcfamerica.org)
1 Administered as an oral therapy, Augtyro is a tyrosine kinase inhibitor (TKI) targeting ROS1 oncogenic fusions. (winway.me)
1,2 Key secondary endpoints include duration of response (DOR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as assessed by Blinded Independent Central Review (BICR), progression-free survival (PFS), and intracranial response in six distinct expansion cohorts, including tyrosine kinase inhibitor (TKI)-naïve and TKI-pretreated patients with ROS1 -positive locally advanced or metastatic NSCLC. (winway.me)
In the phase III FLAURA study, osimertinib reduced the risk of progression or death by 54% versus standard tyrosine kinase inhibitor (TKI) therapy of erlotinib (Tarceva) or gefitinib (Iressa) in patients with EGFR -mutant NSCLC. (onclive.com)
Icotinib is a potent and highly selective oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), and it is used for the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) patients carrying EGFR mutations. (bettapharma.com)

ASP 3026 is a potent anaplastic lymphoma kinase (ALK) inhibitor (IC 50 = 3.5 nM). (tocris.com)
For NSCLC, much of the work in the last decade has been focussed on mutations of the epidermal growth factor receptor (EGFR) and on the abnormal fusion of the anaplastic lymphoma kinase (ALK) being inhibited successfully with EGFR tyrosine kinase inhibitors (TKI) and crizotinib respectively. (amegroups.org)
Initially was developed as a MET inhibitor, crizotinib had activity in anaplastic lymphoma kinase ( ALK ) fusions and ROS1 rearrangements. (parsianpharma.com)
An early result of this search was the discovery of NSCLC driven by activating rearrangements of the anaplastic lymphoma kinase (ALK) and ROS1 . (parsianpharma.com)
Herein, we summarized the novel agents in tyrosine kinase inhibitors especially for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors, checkpoint inhibitors, and other potential immunotherapy aiming to provide a landscape of emerging agents for NSCLC as well as insights and perspectives for the future in anticancer treatment. (biomedcentral.com)
Ensartinib is a novel, potent and highly selective next-generation inhibitor of anaplastic lymphoma kinase (ALK), which has a potency more than ten-times greater than crizotinib in enzymatic assays. (bettapharma.com)
Anaplastic lymphoma kinase tyrosine kinase inhibitors are standard therapeutic agents prescribed for anaplastic lymphoma kinase-positive non-small cell lung cancer, and treatment with these agents has been shown to contribute to long-term survival in patients. (biomedcentral.com)
However, there is no consensus regarding the course of treatment after the onset of anaplastic lymphoma kinase tyrosine kinase inhibitors related drug-induced interstitial lung disease. (biomedcentral.com)
With the identification of gene abnormalities in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), effective ALK tyrosine kinase inhibitors (ALK-TKIs) have been developed for treatment. (biomedcentral.com)
Non-small cell lung cancer (NSCLC) treatment in advanced stage like IIIB, IIIC, and IV is based on several driver mutations analysis including mutations/alterations of the epidermal growth factor receptor, anaplastic lymphoma kinase, ROS1, and PDL-1 expression. (asjo.in)

Since that discovery, multiple studies have demonstrated an incidence of approximately 1% in lung cancers, demonstrated oncogenicity, and showed that inhibition of tumor cells bearing ROS1 gene fusions by crizotinib or other ROS1 tyrosine kinase inhibitors was effective in vitro. (wikipedia.org)
Clinical data supports the use of crizotinib in lung cancer patients with ROS1 gene fusions. (wikipedia.org)
Crizotinib or other ROS1 inhibitors may be effective in other tumor histologies beyond lung cancer as demonstrated by a patient with an inflammatory myofibroblastic tumor harboring a ROS1 fusion with a dramatic response to crizotinib. (wikipedia.org)
A benefit of a small-molecule ALK, ROS1 , and cMET inhibitor, crizotinib, was also shown in this patient group. (wikipedia.org)
this study also confirmed the activity of the ALK/ROS1 /cMET inhibitor crizotinib in ROS1 -positive tumors. (wikipedia.org)
Crizotinib (Xalkori) is a ROS1 inhibitor that also inhibits ALK and MET and is approved by the FDA. (curetoday.com)
Beyond that, if you look at the preclinical data comparing crizotinib and entrectinib side by side, entrectinib is much more potent than crizotinib … So, the hope (is that) we'll see a prolongation in PFS. (curetoday.com)
Crizotinib remains an option for patients with ROS1 fusion. (medscape.com)
The discovery of ALK and ROS1 rearrangements and development of crizotinib provided a personalized treatment option for patients with advanced ALK and ROS1 positive NSCLC. (parsianpharma.com)
ALK and ROS1 share considerable homology, which lets crizotinib to bind to both with strong affinity. (parsianpharma.com)
Only a few years later, crizotinib was the first approved TKI by the US Food and Drug Administration (FDA) for the treatment of advanced NSCLC that has spread to other parts of the body and is caused by a defect in either a gene called ALK or a gene called ROS1. (parsianpharma.com)
Crizotinib is potent MET inhibitor, in addition to inhibiting ALK and ROS1. (parsianpharma.com)
Tyrosine kinase inhibitors (TKIs) such as crizotinib, ceritinib, and entrectinib that target the ROS-1 fusion protein have been effective in individuals with non-small cell lung cancers. (lcfamerica.org)
Repotrectinib is a new-generation drug that inhibits ROS-1 and other receptor tyrosine kinases, and results from in vitroassays suggest that repotrectinib is at least 90-fold more potent than crizotinib and entrectinib. (lcfamerica.org)
About 4 years later, crizotinib (Xalkori), an epithelial-mesenchymal transition (EMT) inhibitor, was granted accelerated approval by the Food and Drug Administration for ALK-positive non-small cell lung cancer (NSCLC), and in 2013, the oral agent won an FDA green light for use in this patient population. (medpagetoday.com)
In 2016, the FDA approved crizotinib for patients with ROS1-positive NSCLC. (medpagetoday.com)
The difficulties we experienced in targeting ALK with crizotinib in neuroblastoma motivated us to find a more potent ALK inhibitor. (emory.edu)
Based on Dr. Mossé's discovery, in 2009 COG launched a clinical trial for children with neuroblastoma that repurposed crizotinib, an ALK inhibitor that was already approved by the FDA to treat adults with a subtype of lung cancer caused by abnormalities in the ALK gene. (emory.edu)
2013). Acquired Resistance to Crizotinib from a Mutation in CD74 - ROS1 . (lightsource.ca)

These initial findings paved the way for more expansive analyses of ROS1 kinase fusions in NSCLC and other cancers. (wikipedia.org)
In patients with NSCLC, approximately 2% are positive for a ROS1 gene rearrangement, and these rearrangements are mutually exclusive of ALK rearrangement. (wikipedia.org)
Similar to ALK-rearranged, ROS1-rearranged NSCLC have younger age of onset and a non-smoking history. (wikipedia.org)
ROS1 expression was found in approximately 2% of NSCLC patients, and its expression was limited to those patients with ROS1 gene fusions. (wikipedia.org)
Table 1: Sampling of ROS1 Rearrangements Observed in NSCLC and Other Cancers. (wikipedia.org)
In phase 1 and 2 clinical trials in patients with ROS1-positive NSCLC,) the overall response rate with entrectinib was about 75 percent, with a comparable response rate in the central nervous system and a progression-free survival (PFS) of 19 months. (curetoday.com)
In an amazingly Short period following the recognition of ALK-positive NSCLC, clinicopathologic features, development of targeted inhibitor drugs, mechanisms of therapeutic resistance, and new generations of treatment were identified. (parsianpharma.com)
PRINCETON, N.J.-(BUSINESS WIRE)- Bristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) approved Augtyro (repotrectinib) for the treatment of adult patients with locally advanced or metastatic ROS1 -positive non-small cell lung cancer (NSCLC). (winway.me)
New treatment options continue to be needed for patients with ROS1 fusion-positive NSCLC that support important clinical goals, including achieving durable therapeutic responses," said Jessica J. Lin, MD, TRIDENT-1 primary investigator and attending physician at the Center for Thoracic Cancers at Massachusetts General Hospital and Assistant Professor of Medicine at Harvard Medical School. (winway.me)
"ROS1 -positive NSCLC patients and their families face a stressful journey because our cancer can be difficult to treat, especially when it spreads to the brain," said Janet Freeman-Daily, co-founder and president of The ROS1ders, a patient advocacy organization. (winway.me)
Augtyro is designed to minimize interactions that can lead to certain forms of treatment resistance in ROS1 -positive metastatic NSCLC patients. (winway.me)
The discovery of ALK gene rearrangements and the development of tyrosine kinase inhibitors (TKIs) that target them have achieved unprecedented success in the management of patients with ALK-positive NSCLC. (medpagetoday.com)
MAPK inhibitors and the combination of BRAF and MEK inhibitors, initially developed in the field of melanoma, are also highly relevant to BRAF- mutant NSCLC. (ajmc.com)
A paradigm shift from the double BRAF/MEK inhibition to combinations with agents with distinct mechanisms of action, such as immune-checkpoint inhibitors, pan-RAF, and selective ERK 1/ 2 inhibitors, is under investigation and may change the therapeutic landscape of BRAF -driven NSCLC," the authors wrote. (ajmc.com)
Importantly, the absence of a striking clinical benefit in RET-oncogene-addicted NSCLC underscores the clear need for the development of more selective and potent RET inhibitors and for a better characterization of concomitant genomic alterations and mechanisms of resistance to RET inhibition in lung cancer patients. (blogspot.com)

Although the most preclinical and clinical studies of ROS1 gene fusions have been performed in lung cancer, ROS1 fusions have been detected in multiple other tumor histologies, including ovarian carcinoma, sarcoma, cholangiocarcinomas and others. (wikipedia.org)
ROS1 fusions were also identified in approximately 2% of adenocarcinomas and 1% of glioblastoma samples in an assessment of kinase fusions across different cancers. (wikipedia.org)
These preliminary data support NVL-520 as a potential best-in-class ROS1-selective inhibitor that may combine, for the first time, potent and selective targeting of diverse ROS1 fusions and secondary ROS1 resistance mutations including G2032R, brain penetrance, and the avoidance of TRK inhibition that can be dose limiting. (weeklyreviewer.com)

Nonetheless, as gene rearrangement events involving ROS1 have been described in lung and other cancers, and since such tumors have been found to be remarkably responsive to small molecule tyrosine kinase inhibitors, interest in identifying ROS1 rearrangements as a therapeutic target in cancer has been increasing. (wikipedia.org)
Gene rearrangements involving the ROS1 gene were first detected in glioblastoma tumors and cell lines. (wikipedia.org)
Among the top 20 receptor tyrosine kinases identified in this analysis, 15 were identified in both cell lines and tumors, and among these were both ALK and ROS1. (wikipedia.org)
Ensatinib has shown good efficacy in in vitro and in vivo studies, including those tumors that are already resistant to clozatinib, and has inhibitory effects on c-Met, TRK 1/ 2/ 3, ROS1, etc. (bettapharma.com)
These data provided evidence that HPV-positive tumors may be more sensitive to chemotherapy and molecular inhibitors that specifically target cell cycle. (moffitt.org)
This dependency, often referred to as "oncogene addiction," renders such tumors highly susceptible to small molecule inhibitors targeting RET. (cliniexpert.com)

Preclinical and clinical work suggests multiple potential mechanisms of drug resistance in ROS1 + lung cancer, including kinase domain mutations in ROS1 and bypass signaling via RAS and EGFR. (wikipedia.org)
There are targeted drugs designed to stop the dangerous activity of a number of rare, cancer-causing mutations, including rearrangements of the ROS1, ALK, RET and TRK genes and mutations of the MET or EGFR genes. (curetoday.com)
In the past decade, applicability of targeted therapy expanded from EGFR and ALK to now include six other actionable mutations- RET , BRAF , ROS1 , MET exon 14, NTRK , and KRAS -with strong enough data to be included in National Comprehensive Cancer Network guidelines . (medscape.com)
BRAF and EGFR inhibitors are targeted therapies that work well together in treating people with BRAF -mutant CRC. (bvsalud.org)
In the SEAMARK study, we will use a treatment combination including a BRAF inhibitor (encorafenib), an EGFR inhibitor (cetuximab) and an immunotherapy (pembrolizumab) in patients with CRC who have a BRAF mutation and deficiencies in the DNA repair mechanism. (bvsalud.org)
Similarly, for third-generation EGFR inhibitors, progression-free survival is now between 1.5 and 2 years. (expertperspectives.com)
This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anticancer activity of BLU-945, a selective EGFR inhibitor, as monotherapy or in combination with osimertinib. (uci.edu)

which both of them have become a successful targets of multiple tyrosine kinase inhibitors (TKIs). (parsianpharma.com)
NVL-520 is a novel brain-penetrant ROS1-selective inhibitor created with the aim to simultaneously overcome the clinical challenges of emergent treatment resistance, off-target central nervous system (CNS) adverse events, and brain metastases that may limit the use of currently available ROS1 tyrosine kinase inhibitors (TKIs). (weeklyreviewer.com)
Currently approved and investigational ROS1 TKIs are important treatment options for advanced ROS1 fusion-positive cancers. (weeklyreviewer.com)
We are excited to present the first look at the safety and clinical activity of NVL-520 from our ARROS-1 clinical trial, which we believe supports NVL-520 as a potential best-in-class ROS1-selective inhibitor that may be capable of overcoming the limitations of current approved and investigational ROS1 TKIs,' said Christopher Turner , M.D., Chief Medical Officer of Nuvalent. (weeklyreviewer.com)
Lorlatinib is a novel third-generation ALK TKI that has been shown to be more potent than second-generation TKIs in biochemical and cellular assays and has the broadest coverage of the identified ALK resistance mutations. (biomedcentral.com)

The experimental drug) entrectinib is a multikinase inhibitor that has activity against ALK, ROS1 and TRK. (curetoday.com)
Background: Entrectinib is a highly potent ATP-competitive and selective inhibitor of tyrosine kinases - Trk A B C, ALK, and ROS1. (currentmedicinalchemistry.com)
Methods: We conduct a literature review of the research studies on the new highly-potent small-molecule entrectinib. (currentmedicinalchemistry.com)

Also inhibits Ack and ROS1 activity (IC 50 values are 5.8 and 8.9 nM respectively). (tocris.com)
It also inhibits EMT and ROS1, a kinase that shares 77% of amino acid sequences of adenosine triphosphate (ATP)-binding sites with the ALK. (medpagetoday.com)
Glutaminase C-IN-1 is an allosteric inhibitor of glutaminase C that inhibits cancer cell growth without affecting their normal cellular counterparts. (csnpharm.cn)

Translational research advances now allow such mutations to be inhibited by either receptor monoclonal antibodies (mAb) or small molecule tyrosine kinase inhibitors (TKI). (amegroups.org)

It is also the first FDA-approved drug designed to target both NTRK and ROS1. (currentmedicinalchemistry.com)

The MET inhibitors are suggested in use in the front-line setting for such patients, rather than immunotherapy and/or chemotherapy. (parsianpharma.com)
BACKGROUND: The undetermined efficacy of the current standard-of-care neoadjuvant treatment, anthracycline/platinum-based chemotherapy, in patients with early-stage triple-negative breast cancer (TNBC) and germline BRCA mutations emphasizes the need for biomarker-targeted treatment, such as poly(ADP-ribose) polymerase inhibitors, in this setting. (bvsalud.org)
Among patients pretreated with one prior ROS1 TKI and no prior chemotherapy (n=56), the ORR was 38% (95% CI: 25 to 52) and the mDOR was 14.8 months. (winway.me)

It is a type of small molecule inhibitor called selective inhibitors of nuclear export (SINE). (ucbraid.org)

In 2007 a ROS1 rearrangement was identified in a cell line derived from a lung adenocarcinoma patient. (wikipedia.org)

ASP 3026 is also offered as part of the Tocriscreen Kinase Inhibitor Library . (tocris.com)
Vorolanib (CM082) is a novel next-generation of multi-target kinase inhibitor, which can inhibit tumor angiogenesis and growth, and can be used in the treatment of many kinds of cancer. (bettapharma.com)
AZ 5704 is a potent and selective ATM kinase inhibitor with IC50 of 0.6 nM. (csnpharm.com)

Pembrolizumab is a checkpoint inhibitor approved for the treatment of MSI-H/dMMR mCRC, and the BRAF inhibitor encorafenib, in combination with cetuximab, is approved for previously treated BRAF V600E-mutant mCRC. (bvsalud.org)
BRAF proteins can help cancer cells grow, and BRAF inhibitors block these proteins to prevent, slow, or stop the growth of the cancer cells. (bvsalud.org)

Tyrosine kinase inhibitors and immunotherapy for lung cancer are the two major areas undergoing rapid development. (biomedcentral.com)
Herein, we summarize emerging agents including tyrosine kinase inhibitors, checkpoint inhibitors, and other potential immunotherapy such as chimeric antigen receptor T cell for non-small cell lung cancer attempting to provide insights and perspectives of the future in anticancer treatment. (biomedcentral.com)
An important unmet medical need is the resistance that we see with tyrosine kinase inhibitors and with immunotherapy. (expertperspectives.com)
The FDA approved a cancer immunotherapy drug, Darzalex (daratumumab), in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy such as proteasome inhibitor (PI) or an immunomodulatory agent therapy3. (canceredinstitute.org)

ROS1 rearrangements are estimated to be roughly half as common as ALK-rearranged NSCLCs. (wikipedia.org)
Q: There are targeted agents available that can treat ROS1 gene rearrangements, and more are being studied in clinical trials. (curetoday.com)
We know that ROS1 rearrangements occur in about 1 to 2 percent of NSCLCs and, fortunately, they're highly (treatable) drivers. (curetoday.com)
Sometimes ROS1 rearrangements have been seen in large-cell and squamous cell carcinoma. (parsianpharma.com)
Unlike ALK and ROS1 rearrangements, RET fusion genes cannot be adequately detected by immunohistochemistry, although fluorescence in situ hybridization and reverse transcriptase PCR are fully complementary diagnostic tools. (blogspot.com)

How are these newer ALK inhibitors being developed to counter resistance? (onclive.com)

Balstilimab is a human monoclonal antibody targeting programmed cell death protein 1 (PD-1), and is an immune checkpoint inhibitor. (bettapharma.com)

Across all evaluated dose levels, NVL-520 exhibited activity in a heavily pre-treated patient population, many of whom have exhausted all available treatment options and would have been excluded from other investigational ROS1 TKI studies. (weeklyreviewer.com)
This is the second Phase 3 trial to open for selpercatinib, a highly selective and potent, oral investigational new medicine in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase. (cliniexpert.com)
Selpercatinib, also known as LOXO-292, is a highly selective and potent, oral investigational new medicine in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase. (cliniexpert.com)

VE-822 is an ATR inhibitor with IC50 of 19 nM in HT29 cells. (csnpharm.com)
PI-103 is a potent inhibitor with low IC50 values against recombinant PI3K isoforms p110alpha (IC50= 2 nM), p110beta (IC50= 3 nM), p110delta (IC50= 3 nM), and p110gamma (IC50= 15 nM), less potent to mTOR/DNA-PK with IC50 of 30 nM/23 nM. (csnpharm.com)
BAY-1895344 is a potent and selective ATR inhibitor with IC50 of 7 nM. (csnpharm.com)

For the treatment of patients with advanced ROS1-rearranged lung cancer, we're trying to move the needle forward by looking at better therapies that target ROS1. (curetoday.com)
These treatments may turn out to be more potent and better able to cross the blood/brain barrier than the therapies already approved). (curetoday.com)
6,7 "As the only approved next-generation TKI for ROS1- positiveNSCLCpatients, Augtyro builds on our legacy of delivering transformational therapies for patients with thoracic cancers. (winway.me)

Importantly, the favorable safety profile and lack of dose reductions or discontinuations due to adverse events reflected in this preliminary data suggest that NVL-520 has the potential to provide deep and durable responses and may be able to move up in the treatment paradigm for patients with ROS1-driven cancers. (weeklyreviewer.com)
The Actuate 1801 Phase 1/2 study is designed to evaluate the safety and efficacy of 9-ING-41, a potent GSK-3β inhibitor, as a single agent and in combination with cytotoxic agents, in patients with refractory cancers. (uci.edu)

The FDA has approved repotrectinib (Augtyro) for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer. (lcfamerica.org)
4,5,6,7 "Based on the data we have seen in the TRIDENT-1 trial, repotrectinib has the potential to become a new standard of care option for patients with locally advanced or metastatic ROS1 fusion-positive lung cancer. (winway.me)

2013). Discovery of a Potent Boronic Acid Derived Inhibitor of the HCV RNA-Dependent RNA Polymerase . (lightsource.ca)

To date, several preclinical models, clinical trials, and retrospective studies have investigated multi-target inhibitors with anti-RET activity in RET-rearranged lung cancer patients. (blogspot.com)

Proto-oncogene tyrosine-protein kinase ROS is an enzyme that in humans is encoded by the ROS1 gene. (wikipedia.org)
The exact role of the ROS1 protein in normal development, as well as its normal physiologic ligand, have not been defined. (wikipedia.org)

AZ31 is a potent and highly selective ATM inhibitor. (csnpharm.com)

ROS1 fusion-positive patients tend to be younger, with a median age of 49.8 years, and never-smokers, with a diagnosis of adenocarcinoma. (wikipedia.org)

10 "Today's approval brings a new treatment option for the ROS1 -positive patient community, which gives us hope for more time with loved ones. (winway.me)

Ultimately, what we need to develop are more effective treatments by either adding additional drugs or developing more potent drugs, and we are beginning to achieve that. (expertperspectives.com)

As we have improved the specificity and potency of agents, the progression-free survival durations have increased from approximately 10 to 12 months with first-generation ALK inhibitors to approximately 3 years for our second- and third-generation ALK inhibitors. (expertperspectives.com)

Emboldened by unprecedented response rates to kinase inhibitors seen in that subset, the oncologic scientists searched for other molecular subsets featuring oncogene addiction. (parsianpharma.com)

Anatomy35

Organisms9

Diseases10

Chemicals and Drugs135

Analytical, Diagnostic and Therapeutic Techniques and Equipment18

Phenomena and Processes47

Information Science1

Tyrosine kinase in9

Anaplastic lympho10

Crizotinib19

NSCLC15

Fusions3

Tumors6

EGFR7

TKIs5

Entrectinib3

Inhibits3

Small molecule tyrosine kinase inh1

NTRK1

Chemotherapy3

Selective inhibitors1

Rearrangement1

Kinase inhibitor3

BRAF2

Immunotherapy4

Rearrangements5

Resistance1

Checkpoint1

Investigational3

IC503

Therapies3

Cancers2

Metastatic2

Discovery1

Activity1

Protein2

Highly1

Fusion-positive1

Treatment1

Treatments1

Progression1

Addiction1