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Find Clinical Trial

 by Agent

by Type of Lymphoma & Treatment Status  

Trials of Interest

New trials since MAY 2019

 
Phase I since 2017  | Phase III since 2008
 

Guidelines at Diagnosis | About Clinical Trials

evidence-based support and information

 

Treatment Overview > Agents that Target Disease Pathways

Last update: 07/10/2019

Alphabetical list of targeted agents
for lymphoma OR CLL: 
INTRODUCTION

Index (A to I redone. See Notice)
By Class (new & under development.

 Terms related to targeted drugs in lay language 

NOTICE:

Over a decade we have converted queries of clinical trials.gov into shortcut URLS. This so users of lymphomation can click once to find trials by agent or other criteria, such as lymphoma subtype. Doing this allows us to also count how many people have clicked the link. Bitley converted the URLs to USA.gov short urls for government sites such as for clinicaltrials.gov, NASA, NOA, etc as a way to show the URL was a reliable USA.gov site.

The Trump administration ended it without, as far as I know, opportunity for public comment. See blog.usa.gov for the notice. We will rebuild some of these queries of clinicaltrials.gov, starting with find trials by agent name A to Z. It will take some time.

Meanwhile, we are also developing queries to locate trials by the class of therapy:

Introduction

We hope that the queries of clinicaltrials.gov provided within will aid patients and their treating oncologists to keep up with emerging investigational studies for lymphoma and CLL.  The notion guiding this way to find trials is that how a drug is thought to work is easier to remember than the arcane names and alias for each drug.

Very few people fully, or even partially, understand drug mechanisms of actions. Even scientists in the field have gaps in knowledge, else we would not need to test them.

Very briefly: Cancer starts with mutations in DNA, which are the "recipes" for cell behavior.  In normal cells the cell behavior is regulated so that cell growth and cell death are balanced.  In cancer cells, the mutations can lead to unchecked growth by turning on or off key PATHWAYS: cell division systems, disabling of the break systems, or by suppression of the immune system. 

Agents that bind to and inhibit these systems (or pathways) can cause the malignant cells to stop growing, shrink. or to go away completely. These good effects must then be weighed against the side effects in clinical trials.

Some types of agents bind to normal molecules on the surface of cancer cells.  These molecules may be present on both normal and malignant cells.  Antibodies that bind to these molecules may have direct killing effects and may also serve to enlist the immune system to kill the cells (Rituxan). 

...Stem cells that do not have these targets can then rebuild the normal blood cells killed by this approach to treatment.  The exploitation of normal cell surface drug target (cd20, cd22, cd19, cd30, CD79b) is a major reason for the relatively fast recent progress against blood cell cancers! 

Other agents bind to block pathways within the cells.  When the drug binds to a pathway driving the malignant behavior the cells may become visible to the immune system, or stop dividing, or die.  

The best future drugs will have high specificity -- causing anti-cancer effects primarily to the tumor cells with fewer off target effects. Because all treatment have side effects and financial toxicity, the ideal future treatments (in my view) will help patients to become free of the disease and of the need for continued treatment - will help patients to live longer with better quality of life.

  (Karl Schwartz, advocate)

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FIND TRIALS BY CLASS OF AGENT for Lymphoma or CLL

Please note that how a drug, or class of drug, is thought to work does not mean it is proven to provide clinical benefit, which is defined as helping the patients to live longer or better.   

Blood cells are inherently sensitive to chemotherapy and radiation, thus, these remain very effective agents in the treatment of blood-cell cancers. These generally work by damaging the DNA of rapidly dividing cells causing the cells to kill themselves (a cell process called apoptosis).

All Agents & Protocols by Phase of Lymphoma or CLL Study

Phase 1 (safety & dose finding)  http://bit.ly/2G3Pt2Q 694
 Phase 2 (activity & safety)  http://bit.ly/2XZEt0k  787
Phase 3 (compare to a standard of care) http://bit.ly/30oso2v 149

 

DIRECTED TO CELL-SURFACE MOLECULES / IMMUNOTHERAPY

Antibody-drug conjugates studies http://bit.ly/2J4Dq5M  30
 as of June 28, 2019:  3 of 30 in phase 3
Typically given by vein on a fixed schedule
Binding molecule on surface of tumor cell type, releasing toxin.
Examples: Polatuzumab Vedotin (binding to CD79b) Brentuximab Vedotin (binding cd30)

Bi-specific antibodies studies http://bit.ly/2KrnbCY 18
 as of June 28, 2019: 3 of 18 in phase 3
Antibody-directed
immunotherapy
Typically given by vein on fixed schedule
Binding 2 molecules on surface of lymphocytes)
Example: Blinatumomab binding CD19 on b-cells and CD3 on T-cells (a t-cell engager)

Monoclonal antibodies studies http://bit.ly/2Y323WN 153
 as of June 28, 2019:  13 of 153 in phase 3
Antibody-directed Immunotherapy
Typically given by vein on a fixed schedule.
Binding to molecules on the surface of lymphocytes such as cd20, or cd19
Example: Rituxan

Radioimmunotherapy studies http://bit.ly/2N1crxu 6
 as of June 28, 2019:  3 of 6 in phase 3
Antibody-directed
Immunotherapy with radiotherapy
Given by vein on fixed schedule - about 1 week.
Antibody-radiation conjugate, binding molecule on surface of b-cell exposing bound and nearby cells to radiation)
Example: Zevalin

DIRECTED TO INTERNAL CELL PATHWAYS

BCL-2 inhibitors studies http://bit.ly/2YbuJwS  76
 as of June 28, 2019: 10 of 76 in phase 3
Pathway-directed
Given by mouth; variable schedule
Binding to internal pathway of b-cells involved in prolonged tumor persistence
Examples: Venetoclax
BTK inhibitors studies  http://bit.ly/31Pdxzq 47
as of June 28, 2019: 2 of 47 in phase 3
Pathway-directed
Given by mouth; usually until progression or unacceptable toxicity
Binding to internal pathway of b-cells involved in b-cell receptor (BCR)
Examples: Ibrutinib, Acalabrutinib
ITK inhibitors studies http://bit.ly/2RuzY8j 1
 New: as of June 28, 2019:  0 of 1 in phase 3
Pathway-directed
Given by mouth until progression or unacceptable toxicity
Binding toTCR signaling through ITK, which is expressed in a variety of T cell lymphomas including PTCL, CTCL, ALCL, and in a subgroup of T lymphoblastic leukemia/lymphoma. Example:  CG-806
PI3k inhibitors studies  http://bit.ly/31Pdxzq 32
as of June 28, 2019: 2 of 32 in phase 3
Pathway-directed
Given by mouth or by vein (depending on type); usually until progression or unacceptable toxicity
Binding to internal PI3K pathway having a role in cell metabolism, growth, migration, survival and angiogenesis.
Examples: Copanlisib, Umbralisib, Parsaclisib 

DIRECTED TO EPIGENETIC PATHWAYS

Epigenetic Or Histone Deacetylase OR HDAC  http://bit.ly/2Xi8CbR  29
 as of June 30, 2019: 4 of 29 in phase 3
Binding to internal pathway that control gene expression, such as by activating tumor suppressor genes.
Examples: Romidepsin, Abexinostat, Vorinostat

IMMUNOTHERAPIES

Immune modulating studies http://bit.ly/32g2PlT 155
 as of June 28, 2019: 13 of 153 in phase 3
Variety of agents and mechanisms of actions that modify the immune system to fight cancer  
Examples: Lenalidomide, UTOMILUMAB, Umbralisib ...
Immunotherapy excluding CAR T studies http://bit.ly/2Y5Nvpq 64
 as of June 28, 2019 8 of 64 in phase 3.
Wide range of agents and mechanisms of actions that induce the immune system to fight cancer    
CAR T-cell studies http://bit.ly/2Ihqxq9   119
 as of June 28, 2019:  5 of 119 in phase 3
Programmed T-cell immunotherapy
Given by vein -  typically a 1 time infusion.  
The engineered T-cells are modified to bind to molecules on the surface of lymphocytes.  Can require bridge treatment to allow time to harvest and modify the cells
Examples: Tisagenlecleucel, YESCARTA, YTB323 (rapid production CAR T-cells)

IMMUNE CHECKPOINT INHIBITORS

PD-1/L checkpoint inhibitor studies http://bit.ly/2IXDQem 38
 as of June 28, 2019:  2 of 38 in phase 3
Antibody-directed Immunotherapy / immune modulation
Given by vein on fixed but typically long term schedule.
Binding to receptors on the tumor and t-cells that inhibit immune activation of t-cells against tumor cells.  Particularly active in Hodgkin lymphoma.
Examples: Atezolizumab,  Pembrolizumab

CD47 checkpoint inhibitor studies  http://bit.ly/2JcwWlu  4 of 7 phase 3

CD47 is expressed on don't eat me" cells in microenvironment  "Tumors may evade destruction by the immune system by upregulating CD47, a marker of self, that functions as a myeloid immune checkpoint in cancer.
Examples: Hu5F9-G4, ALX148

CANCER VACCINES

Vaccine studies  http://bit.ly/31NtUwt  26
 as of June 28, 2019:  0 of 26 in phase 3
Immunotherapy
Typically given under the skin as an injection of a tumor-specific antigen.  The objective is to promote or amplify the immune system recognition of the tumor as not belonging in order to prevent relapse while in remission from standard therapies.

More classes of agents to be added soon.

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Also see:

About Targeted Drugs

7 Reasons to Consider Trials based on our unique clinical circumstances

Since choosing a trial is complicated, we believe it's important also to consult specialists.  To assist we provide:

Trial Talk - specialists to consult about trials

 Study drug name 1 / alternate name 
(short name for target or mechanism) 2
Find Trials 3 

1  links to background articles
2  mechanism or target
3  lists clinical trials for agent

REDONE (A-H)

ABT-199 venetoclax (activates apoptosis - programmed cell death - through bcl2 pathway)  http://bit.ly/2KchVmK | Full prescribing info for CLL 76

Abexinostat  (oral, pan HDAC inhibitor / epigenetic -  activating or quieting genes to induce tumor cell death) http://bit.ly/2K8yXlD 4

Acalabrutinib (ACP-196) (inhibits btk / B-cell receptor pathway - an overactive pathway in b-cell lymphomas) http://bit.ly/2KHQhgT  23

ADCT-301 (anti-CD25-PBD antibody-drug conjugate)  NCI Drug Dictionary http://bit.ly/2F3aw4R 1

Adcetris  / SGN-35 / brentuximab vedotin  (antibody-drug conjugate: anti-cd30 + antitubulin - more selective delivery of a toxin to cancer cells)   http://bit.ly/31sk8zA

ADCT-301  (interleukin-15-based superagonist, induces memory CD8) http://bit.ly/2wV8TSd 3

Adcetris Ofatumumab /  Arzerra cd20 antibody approved for CLL http://bit.ly/2X4Dmw1 5

Atezolizumab (immune checkpoint antibody - pd-1 pathway) http://bit.ly/2IBbnLg 15

Azacitidine (epigenetic) http://bit.ly/2wM7yxg 15

Belinostat PXD101 (epigenetic - recently approved for t-cell lymphoma) http://bit.ly/2KgQ8RV 1

BET protein inhibitor -  BET family regulate the transcription of growth-promoting genes) http://bit.ly/31sH69V 1

Betalutin  (Lu-tetraxetan-tetulomab) radioimmunotherapy antibody targeting cd37 http://bit.ly/2IDK3vF 3

Bendamustine / Treanda (cytotoxic) http://bit.ly/2XIhBze 60

PI3K inhibitor class of agents - BCR pathway) http://bit.ly/2KhjGyO 10

Blinatumomab (BiTe) cd3 cd19 bi-specific antibody http://bit.ly/2F8pyq1 41

Brentuximab Vedotin (anti-cd30 antibody-drug conjugate) http://bit.ly/2RezIu5 50

CC-122  (immune-modulating, pleiotropic pathway modifier) http://bit.ly/31sUPxw 2

CART T-cell therapy (Chimeric antigen receptor adoptive immunotherapy)  http://bit.ly/2Ihqxq9   119

Cerdulatinib (Syk\Jak Inhibitor / PRT062070)  http://bit.ly/2KkdztB 1

Cirmtuzumab (Anti-ROR1 Mab) http://bit.ly/2IeFXLB 1

Copanlisib / BAY 80-6946 (PI3Kα/β inhibitor given by vein) http://bit.ly/2KOQgYk 14

CPI-613 (targets mitochondrial metabolism) http://bit.ly/2WEGla2 1

CUDC-907 (dual inhibitor of PI3K and HDAC) http://bit.ly/2wNwXXp 1

Daratumumab  (anti-cd38) http://bit.ly/2L09r1r 4

Duvelisib / IPI-145 (PI3K)-delta / PI3K-gamma) http://bit.ly/2x0gaAu 6

Entospletinib (SYK inhibitor in BCR pathway)  http://bit.ly/2MXKczG 1

EZH2 inhibitors (epigenetic pathway that contributes to abnormal growth) http://bit.ly/2MTam6u 2

EPZ-6438 (EZH2 Histone Methyl Transferase [HMT] Inhibitor) http://bit.ly/2Y7xxuQ 5

Hu5F9-G4 (5F9) humanized antibody targeting CD47, a don�t eat me signal http://bit.ly/2WOxRlM 2

HMPL-689 (PI3K delta inhibitor)  http://bit.ly/2Y4oJ9q  2

Ibrutinib (inhibits b-cell receptor / btk pathway) http://bit.ly/2N2oHO0 109

Idasanutlin (p53 tumor suppressor gene activator) http://bit.ly/2XmS8OJ 1

Idelalisib (PI3K kinase inhibitor / b-cell receptor pathway)  http://bit.ly/2x3EKR3  12

INCB050465 / Parsaclisib  oral (PI3Ks inhibitor - same class as Idelalisib)  http://bit.ly/2J1Nv3o 6

Inotuzumab Ozogamicin (cd20 antibody-drug conjugate) http://bit.ly/2x5B4hv 19

Ipilimumab anti-CTL-A (MXD-010)  (Immune checkpoint blockade) CTL-A t-reg http://bit.ly/2ZJjQ67 12

Isatuximab (anti-CD-38 antibody) http://bit.ly/2RqnYVw  2

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TODO:
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JNJ-64052781 (Humanized CD19 x CD3 Dual-Affinity Re-Targeting Protein) 
Find Trials  
| NCI Drug Dictionary
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Lirilumab (NK-cell agonist) Find Trials | Report
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Lenalidomide / Revlimid (immune modulation and direct activity)  Find trials 
Our topic
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MEDI-551 (humanized cd19 antibody) Find trials
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MEDI-570 (anti-ICOS antibody for t-cell lymphoma) Find Trials
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Mogamulizumab / POTELIGEO� anti-CCR4 antibody, approved in Japan for CCR4-positive adult T-cell leukemia-lymphoma. Find trials
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Monalizumab (CD94/NKG2A checkpoint mab) for| CLL OR lymphoma Find Trials 
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MOR00208 /XmAb5574)  (cd19 antibody) Find Trials 
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MEDI-570 (Anti-ICOS Monoclonal Antibody) for Peripheral T-cell Lymphoma Follicular Variant or Angioimmunoblastic T-cell Lymphoma
 Study of Interest 
bullet
MLN9708 (Ixazomib, GATA-3 inhibitor) for Relapsed/Refractory Cutaneous and Peripheral T-cell Lymphomas Trial of interest
bullet
MT-3724 (CD20-specific Engineered Toxin Body ) Find Trials

- NCI Drug Dictionary http://bit.ly/2iXLewi
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Obinutuzumab / GA-101 (next gen cd20 antibody)  Find trials 
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Palbociclib (oral, reversible, selective, small-molecule inhibitor of cyclin-dependent kinases (CDK) -- of interest for MCL)  Find Trials
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PD1/L antibodies (removes block on immune system - immune checkpoint blockade)  Find trials | Open trials only

-
Atezolizumab  / MPDL3280A (pd-1 pathway) Find Trials
  NCI Drug Dictionary http://bit.ly/2vZJdRz

- Nivolumab (immune checkpoint blockade) in  Lymphoma Trial of Interest

- Pembrolizumab /
CT-011) / BMS-936558  | Lambrolizumab (Merck)
  NCI Drug Dictionary http://bit.ly/2eWHQOa
 
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PF-05082566 (immunotherapy - anti-4-1BB agonistic antibody targeting the immune checkpoint molecule 4-1BB (CD137) Find Trials  | Report
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Polatuzumab Vedotin (cd22 drug-antibody conjugate) Find trials 

Polatuzumab Vedotin With cd20 antibody With Bendamustine in Relapsed or Refractory Follicular DLBC Lymphoma Trial of interest
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Pomalidomide  (Lenalidomide derived - Immune modulating) Find trials
bullet
PNT2258 (first-in-class DNAi -- BCL-2-targeted liposomal formulation of a 24-base DNA oligonucleotide )  Find trials
bullet
REGN197 (CD20xCD3 bispecific antibody) - Find Trials 

Regeneron [ REGN1979 - CD20xCD3 bispecific antibody] 8 in 10 complete responses in relapsed or refractory follicular lymphoma trial | FierceBiotech http://bit.ly/2LL5DiV 
 
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Romidepsin  (FDA approved, HDAC inhibitor) Find trials  

Romidepsin + Pralatrexate (novel chemo)  in Relapsed/Refractory Lymphoid Malignancies - PTCL only for expansion phase Trial of interest
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RP6530 (dual PI3K inhibitor) Find trials
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RXDX-106 Oral Immunomodulatory Tyrosine Kinase Inhibitor - Find trials 
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SAR 245409 oral pan-inhibitor of PI3K Find trials
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Selinexor  /KPT-330
(activates tumor suppress gene  Find trials
|  Safety report | Report

NCI Drug Dictionary http://bit.ly/2x5nKvE  
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TAK659  (Syk inhibitor) Find Trials
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Tazemetostat /  EZH2 inhibitors (inhibits an epigenetic pathway that contributes to abnormal growth)   Find Trials
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TGR-1202 (PI3k Delta Inhibitor) Find Trials

TGR-1202 + Ibrutinib in Patients With Select B-Cell lymphoma http://1.usa.gov/1zvYgmu

TGR-1202
(PI3K Delta Inhibitor) With Brentuximab Vedotin for Hodgkin's Lymphoma Patients�
Trial of interest
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TRU-016 (cd37 antibody) Find trials
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Ublituximab (next gen cd20 antibody) Find Trials
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Umbralisib  (next gen PI3Kδ Inhibitor)  Find Trials

Shows Early Promise in CLL and Lymphoma http://bit.ly/2GOQSbt
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Utomilumab (immune adjuvant) Find trials

Phase I Study of Single-Agent Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Patients with Advanced Cancer  http://bit.ly/2Ejlrbh  
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varlilumab   (cd27 immune modulating )  Find Trials
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Veltuzumab / Immu-106 / Ha20  (next gen cd20 antibody)  Find trials
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Venetoclax | ABT-199  / (activates apoptosis - programmed cell death - through bcl2 pathway)  Findtrials
Full prescribing info for CLL
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Vidaza � / 5-Azacytidine (epigenetic - activating or shutting off genes) Find trials 
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YM155 (Survivin inhibitor)  Find Trials >
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Zevalin /(Ibritumomab tiuxetan)  (anti-CD20 + Yttrium 90 ) cd20 Find trials

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Terms related to targeted therapies

The purpose is to introduce terms used for targeted therapies for lymphoma

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Cancer is caused by genetic abnormalities or defects in genes called mutations.

Genes are recipes that our cells follow to make cellular proteins

These proteins lead to signals within the cell that determine (or
drive) the cell behavior. 

... The signals involve many parts of the cell called
molecular pathways.  (Analogy: the electrical system in an automobile is similar to a pathway; distinct from the fuel system.

Mutations in key genes (oncogenes) can cause the affected cell to divide too rapidly and/or to persist too long

This so-called malignant behavior, can lead to the accumulation of the cancer cells called
tumors.
 
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An effective targeted drug is one that binds to a molecule of tumor cells leading to stopping the growth or tumor cell death. 

For this reason targeted therapy is sometimes called molecular or precision medicine. 

The molecule or target that the drug binds to can be external or internal.
 

An external target is typically a receptor that is on the surface of the cell that's unique to the type of cell or tumor cell, such as cd20 in b-lymphocytes. 

An internal target is typically a molecule inside the cell that is involved in a signaling pathway that is overactive because of a mutation in the gene.

The best targeted drugs have good
specificity and affinity.  Specificity means the target is unique to the tumor cell.  Affinity means how well the drug binds and remains bound to the target.  A drug with high specificity will have less off-target effects (side effects).  A drug with high affinity is more likely to be active against the disease.
Limitations and considerations
That a study drug is  targeted does not mean it will prove to be effective or safe for a given type of lymphoma or cancer when tested in clinical trials. 

Important questions for patients, and consideration for referring physicians:

1) Is the targeted agent first-in-class (never before tested in humans), or
has a similar agent proven effective in clinical tests in patients with your type of lymphoma?  

2) Is there is a companion diagnostic test to help determine if the target exists based on your tumor sample.
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The molecular target might vary leading to good or poor binding.
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The internal pathway might not be driving the malignancy, or the tumor cells might adapt leading to a limited activity against the behavior of the cells.

Or, the external
receptor might not be related to cell growth or survival.
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The targeted agent might have off-target effects (binding to similar molecules on normal cells) leading to toxicity.
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The targeted agent might not be safe or tolerable at a dose needed to have anti-cancer effects.

Note:  When testing targeted drugs that have been approved in other types of cancer, the clinically active and safe dose will be based on prior clinical experience.  Therefore the recommended dose and risks will be better understood and can be monitored for with more assurance.

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Other terms (coming soon)

Genes have different names, such as BRAF.  Oncogenes are genes that can lead to cancer when mutated.  The changes/  rearrangements / mutations to genes can take place in different portions of the gene (codon, exon), leading to activation of different pathways. 

Most targeted drugs inhibit the pathway ... do not correct the gene mutation.

The changes to genes leading to cancer are almost always acquired (somatic), not inherited (germline).

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codon
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exon
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phosphorylation
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cellular signal transduction
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Recurrent mutations in exon NUMBER of GENE NAME (eg. BRAF)
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wild type MUTATION NAME (BRAF).
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GENE NAME rearrangements (mutations) fuse the kinase domain NAME with a partner gene which leads to constitutive activation of the NAMED pathway

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Further reading?

What is a gene mutation and how do mutations occur? - Genetics Home Reference http://1.usa.gov/1E8ACZP

 
Disclaimer:  The information on Lymphomation.org is not intended to be a substitute for 
professional medical advice or to replace your relationship with a physician.
For all medical concerns, you should always consult your doctor. 
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