Adenovirus
|
See Immune
Therapies
|
Adoptive
Immunotherapy
|
See Immune Therapies
|
Antiangiogenic
|
See Antiangiogenic
|
Anti-Bcl-2
(antisense)
Oblimersen
Type: genetic / molecular
|
Antisense
ASCO
| ASH
| Medscape
| ClinicalTrials.gov
| PubMed
Bcl-2 is a protein
over expressed by a mutated gene in many lymphomas. This protein seems to prevent
cell death (apoptosis) and contribute to drug resistance. Drugs that interfere with the
expression of this protein may induce the tumor cells to die and/or make other treatments
more effective.
 |
|
| Liposomal
delivery of antisense oligonucleotides for efficient
downregulation of Bcl-2 and induction of apoptosis. Cancer Biother
Radiopharm. 2002 Jun;17(3):281-9.
PMID: 12136520 PubMed
|
| Antisense
drug G3139 for NHL reduces target protein levels Doctor's Guide
|
| cDNA microarray evaluation of non-Hodgkin's
lymphoma cells reveals multiple changes in gene expression
profiles induced by Bcl-2 antisense (GenasenseTM). ASCO
2002 Abstract 1905
|
|
Anti-BLyS
Type: biologic / molecular
|
Anti-BLyS
(B lymphocyte stimulator) is a newly
identified protein that may provide a target for treatment of b-cell lymphomas.
"BLyS is made by immune-cells called monocytes and macrophages.
When monocytes and macrophages are activated, BLyS is released and
binds to a receptor found only on B cells." - Human Genome
Sciences
| BIOMARKER/TARGET: Expression of BLyS and its receptors in B-cell non-Hodgkin lymphoma: correlation with disease activity and patient outcome.
www.bloodjournal.org
In summary, we believe that BLyS represents an
important target in B-cell lymphoma and strategies to
inhibit BLyS could therefore translate into important
therapeutic modalities.
|
|
|
|
|
| BLyS and BLyS receptor expression in non-Hodgkin's lymphoma.
Exp Hematol. 2002 Feb;30(2):135-41. PMID: 11823048 PubMed
|
| Radiolabeled BLyS protein (LR131) inhibits neoplastic B cell
growth in vivo Year: 2002 Abstract No: 39
|
|
Anti-idiotype antibodies
|
See Immune
Therapies
|
Anti-PKC-a
Type: biologic / targeted
|
PKC-a is a protein important in the continued
development and growth of cancer cells. PKC-a is a member of the PKC
family, a group of closely related signal transduction proteins, or
proteins that regulate the flow of information in and out of cells,
and control cell reactions to environmental stimuli. The PKC family
plays a role in normal cell function, and is also involved in abnormal
cell growth.
| Protein kinase C inhibitors. Curr Oncol Rep.
2002 Jan;4(1):37-46. Review. PMID: 11734112 - PubMed
| Related
Abstracts
|
| Actions of the selective protein kinase C
inhibitor PKC412 on B-chronic lymphocytic leukemia cells in vitro.
Haematologica. 2002 Feb;87(2):167-76. PMID: 11836167 PubMed
|
|
anti-VEGF
(Mab)
Type: biologic / antiangiogenic
|
|
Antibodies
Monoclonal antibodies (Mab)
Type: biologic / immunotherapy
|
Antibodies
are proteins that when
infused in the patient seek and bind to "matching" receptors on cancer
cells. There are many antibodies being developed for NHL:
Due to the size of this category, we
moved it to it's own page.
|
See Antibodies for
Lymphoma |
|
See Rituxan |
|
Anti-CD74
antibody - internalizing properties prnews
"In yet another presentation, Immunomedics' scientists showed that this *rapidly internalizing CD74 antibody*
was very effective in killing human NHL cells in culture and NHL tumors growing in mice when the
antibody is conjugated with the anticancer drug, doxorubicin. Dr. Horak commented: "Unexpectedly high
efficacy in this preclinical model was found with a single injection of this antibody-drug conjugate, even in
advanced disease."
Cure of SCID Mice
Bearing Human B-Lymphoma Xenografts by an Anti-CD74
Antibody-Anthracycline Drug Conjugate. Clin Cancer Res. 2003 Dec
15;9(17):6567-71. PMID: 14695162
| Related
articles
|
|
|
Apoptosis
Programmed cell death as signaled by the nuclei in
normally functioning cells when age or state of cell health and
condition dictates.
|
| Pan-Bcl2 Family Inhibitor GX15-070 newswire.ca
GX15-070 is a small molecule specifically designed to inhibit
all relevant members of the Bcl-2 protein family, a validated
cancer target, thus restoring the natural cell death process of
apoptosis.
|
|
Arsenic
trioxide
Type: apoptotic & differentiation
|
Arsenic
trioxide may induce cell death
(apoptosis) and normalization (differentiation) thru novel pathway(s). Approved for
leukemia.
|
Bryostatin
Type: cytotoxic and immunomodulatory
|
Bryostatin
- Possible mechanism of
action: "Bryostatin-1 is believed to bind to the regulatory
domain of the PKC enzyme suggesting a mechanism of action distinct
from other kinase modulators in development." gpc-ag.com
|
ASH: Bryostatin Less Than Impressive in Chronic Lymphocytic
Leukemia and Indolent Non-Hodgkin's Lymphoma DoctorsGuide
|
|
BR
2778 (Pixantrone)
Type: novel aza-anthracenedione
|
"BBR
2778 is a novel analogue of anthracenediones which acts by DNA
intercalation and inhibition of DNA topo-isomerase II." ASCO
|
Phase I study of BBR 2778, a new aza-anthracenedione, in
advanced or refractory non-Hodgkin's lymphoma. Ann Oncol. 2001
May;12(5):661-7 abstract
|
|
c-myc
Type: biologic / molecular target
|
c-myc is a gene that's
over expressed in a variety of
malignancies including lymphomas, and leukemias. It's thought that the
oncogenic (cancer promoting) "properties of C-Myc arise from gene
amplification or chromosome translocation." Anti-c-myc
oligonucleotides are being investigated as potential treatments that
target this gene.
|
Cell cycle
arrest
Type: biologic / molecular
|
"The
mechanisms underlying this effect are mediated by the adenosine
A3 receptor and involve cell cycle arrest and the
inhibition of the telomeric signal, the scientists have determined."
|
Combination
treatments
|
Numerous combinations and sequences of therapies are possible. Of interest to
many is the
possibility of combining low toxic therapies to better manage indolent NHL without
suppressing bone marrow function or burning treatment bridges.
|
|
| Dipeptidyl
peptidase inhibitor PT-100: An anti-tumor small molecule that
amplifies immunity (PT-100) ASCO
2003
|
|
|
| Dynavax Initiates First Human Trial Of ISS
Immunotherapy And Rituxin®
(Rituximab) press
release
|
|
CpG oligonucleotides
Type: DNA / immunotherapy
|
"CpG
activates the immune system in the way it evolved to be activated, by
detection of bacterial products. You activate a well-orchestrated
symphony of responses that synergize with each other." Everything
enters on cue: cells, cytokines, and actions. Toxicity is minimal.
Immune factors, although great medicines, drive "an artificial,
disorganized response. You have to use very high doses to get any
activity, and because of that, you also get a lot of toxicity."
|
Background: Coley Toxin's Hidden Message
From a 19th century mystery comes a potential new class of drugs:
CpG oligonucleotides
|
|
Boosting Mabs and vaccines? CpG-DNA activates dendritic cells
in vivo: T helper cell-independent cytotoxic T cell responses to
soluble proteins. Eur J Immunol. 2000 Dec;30(12):3591-7. Related
abstracts
|
|
CP461
/ OS1-461
(SAANDs)
Type: biologic / apoptotic
|
Selective
apoptotic anti-neoplastic drugs (SAANDs). Induce apoptosis in a broad range of cancerous
and precancerous cells via inhibition of cyclic GMP phosphodiesterase (cG PDE) and
activation of PKG. (* Safe profile, oral administration.)
|
Good tolerability profile for OSI-461 ( selective
apoptotic antineoplastic drug (SAAND)) in advanced cancer patients
accessoncologia.com
2003
|
|
|
|
Cyclin dependent kinases
(CDKs)
Type: biologic / molecular
|
Cyclin dependent kinases (CDKs)
are regulators of cell
cycle progression.
|
|
| Flavopiridol
- PubMed Phase 2 trials with infusional flavopiridol in several tumor types, other
schedules and combination with standard chemotherapies are being assessed.
|
|
Denileukin diftitox (ONTAK)
type: targeted
|
Denileukin diftitox (den-i-LOO-kin
DIF-ti-tocks) is a fusion protein designed to direct the cytocidal
action of diphtheria toxin to cells which express the IL-2
receptor. The human IL-2 receptor exists in three forms, low
(CD25), intermediate (CD122/CD132) and high (CD25/CD122/CD132)
affinity. The high affinity form of this receptor is usually found
only on activated T lymphocytes, activated B lymphocytes and
activated macrophages.
Malignant cells expressing one or more of the subunits of the IL-2 receptor are found in certain leukemias and lymphomas including cutaneous T-cell lymphoma (CTCL)1. Ex vivo studies suggest that denileukin diftitox interacts with the high affinity IL-2 receptor on the cell surface and inhibits cellular protein synthesis, resulting in cell death within hours."
[1]
-
-
About side effects Medscape
-
Interim analysis of a phase II study of denileukin diftitox (ONTAK) for B and T-cell non-Hodgkin's lymphoma
Abstract No: 2292
-
Remission of follicular non-Hodgkin's lymphoma
with denileukin diftitox (ONTAK) after progression during
rituximab, CHOP and fludarabine therapy. Leuk Lymphoma. 2003
Apr;44(4):731-3. PMID:
12769354
-
Denileukin diftitox for GvHD tops news at Tandem
BMT hemonctoday.com
Mar 2004
|
Gallium
Nitrate
Type: targeted
|
Gallium
Nitrate (Ganite®) was previously received FDA approval as treatment
for cancer-related hypercalcemia. "Gallium nitrate
causes little myelosuppression and is therefore well tolerated by
patients with advanced disease who have received extensive prior
therapy. Given its unique mechanism of action, the high level of
single-agent activity in published clinical trials, the absence of
significant myelosuppression, and the potential lack of
cross-resistance, further clinical study of gallium nitrate both alone
and in combination with other active agents is warranted."
3
-
-
Gallium nitrate in the treatment of lymphoma.
Semin Oncol. 2003 Apr;30(2 Suppl 5):25-33. Review. PMID:
12776257
About the gallium nitrate (for treatment of
hypercalcemia) MedlinePlus
Identification
of biomarkers for tumor sensitivity and resistance to Ganite aacr03.agora.com
|
Histone deacetylase
(HDAC) inhibitor
Type: biologic / molecular
|
"Deacetylation
of histones results in condensed chromatin structure and repression of
gene transcription." [1]
PXD101 (example) is a small molecule
HDAC inhibitor being investigated for its role in the treatment of a
wide range of solid and hematologic malignancies either as a
single-agent, or in combination with other active anti-cancer agents,
and is currently being evaluated in a Phase II clinical trial for the
treatment of multiple myeloma. HDAC
inhibitors represent a new mechanistic class of anti-cancer
therapeutics that target HDAC enzymes,
and have been shown to: arrest growth of cancer cells (including drug
resistant subtypes); induce apoptosis, or programmed cell death;
promote differentiation; inhibit angiogenesis; and sensitize cancer
cells to overcome drug resistance when used in combination with other
anti-cancer agents. In August 2004, 5
Clinical
experience with the histone deacetylase (HDAC) inhibitor
suberoylanilide hydroxamic acid (SAHA) in heavily pre-treated
patients with hematological malignancies - ASCO
2003
Inhibitor
of histone deacetylation, depsipeptide (FR901228), in the
treatment of peripheral and cutaneous T-cell lymphoma: a case
report - full text Blood
2001
The histone deacetylase inhibitor Trichostatin A modulates CD4+ T cell responses
pubmedcentral.nih.gov
Inhibitor of histone deacetylation,
depsipeptide (FR901228), in the treatment of peripheral and
cutaneous T-cell lymphoma: a case report.
Blood. 2001 Nov 1;98(9):2865-8. PMID:
11675364
-
New Preclinical Data on HDAC Inhibitor PXD101
Demonstrates Down Regulation of Common Mechanism of Cancer Therapy
Resistance topotarget.com
pressrelease_20042005.pdf
|
Immune
therapies
Type: immunotherapy
|
Technologies
that seek to enhance or direct the immune system to fight
cancer.
We have moved this growing
section to a separate page:
|
Immune-based
therapies for lymphomas - PAL
|
|
Immunotoxin
bound
to antibody
Type: targeted immunotherapy / cytotoxic
|
A new fusion
toxin, BL22, targets the CD22 antigen and shows marked activity in the treatment of hairy
cell leukemia. Other cd-22 b-cell lymphomas may well respond.
|
Measles virus
Type: immunotherapy
|
Safe, live
attenuated measles virus (MV) vaccines regress NHL tumors in mice.
|
Microtubules
Type: molecular
|
Microtubules
are structures involved in cell division. Anti-microtubule drugs
disturb the assembly of the microtubules and thus prevent the cell
from dividing. In normal cell growth, microtubules are formed when a
cell starts dividing. Once the cell stops dividing, the microtubules
are broken down or destroyed. Anti-microtubule drugs stop the
microtubules from breaking down; cancer cells become so clogged with
microtubules that they cannot grow and divide. (NCI)
|
|
| TARGETING THE MICROTUBULE APPARATUS IN INDOLENT
AND MANTLE CELL LYMPHOMA WITH THE NOVEL EPOTHILONE ANLOG BMS
247550 INDUCES MAJOR AND DURABLE REMISSIONS IN VERY DRUG RESISTANT
DISEASE ASCO
2005 | ClinicalTrial
|
|
|
|
Mitoguazone
Type: apoptotic
|
"Mitoguazone (methylglyoxal
bisguanylhydrazone, methyl-GAG or MGBG) is a synthetic polycarbonyl
derivative with activity in patients with Hodgkin's and non-Hodgkin's
lymphoma, head and neck cancer, prostate cancer, and esophageal
cancer. Mitoguazone has also recently been documented to have activity
in patients with AIDS-related lymphoma. Among anticancer drugs,
mitoguazone has a unique mechanism of action via interference with the
polyamine biosynthetic pathway." [1]
Mitoguazone induces apoptosis via a
p53-independent mechanism.
Anticancer Drugs. 1998 Aug;9(7):635-40. PMID: 9773808 PubMed
| Related
abstracts
|
Paclitaxel
Type: apoptotic
|
|
A phase I and pharmacokinetic (PK) study of
PEG-paclitaxel in patients with advanced solid tumors ASCO
|
|
Resveratrol (pigment in red grapes) modifies the
expression of apoptotic regulatory proteins and sensitizes
non-Hodgkin's lymphoma and multiple myeloma cell lines to Paclitaxel-induced
apoptosis. Mol Cancer Ther. 2004 Jan;3(1):71-84. PMID:
14749477 | Related
articles
|
|
PPAR-gamma
Type: apoptotic
|
"PPAR-gamma agonists may serve
as a counterbalance to the stimulating effects of PGE2, which promotes
B-cell differentiation. The use of prostaglandins, such as 15d-PGJ2,
and synthetic PPAR-gamma agonists to induce apoptosis in B lineage
cells may lead to the development of therapies for fatal
PGE2-resistant B lymphomas.
" [1]
PPAR-gamma-mediated regulation of normal and
malignant B lineage cells.
Ann N Y Acad Sci. 2000 Apr;905:97-109.
PMID: 10818446 PubMed
| Related
Abstracts
|
Prodigiosin
Type: apoptotic
|
Prodigiosin induces apoptosis of B and
T cells from B-cell chronic lymphocytic leukemia. Leukemia. 2003
Apr;17(4):746-50. PMID: 12682632 - PubMed
|
Velcade
(Proteasome
inhibitor) PS-341 / Bortezomib
Type: biologic / molecular / apoptotic
|
Thought to
interfere with the function of an important cellular protein complex, and provokes cells
to program their own destruction. "The
results from this study (phase I) are exciting because PS-341 was able to benefit several
patients who were not helped by standard chemotherapy," Orlowski said. PS-341 seemed
particularly active in two diseases: multiple myeloma and non-Hodgkin's lymphoma. Also
called LDP-341
|
Drug-induced
cutaneous vasculitis (inflammation of the blood vessels) in
patients with non-Hodgkin lymphoma treated with the novel
proteasome inhibitor bortezomib (Velcade): a possible surrogate
marker of response? Br J Haematol. 2006 Aug;134(4):391-8. PMID:
16882131
|
|
Phase II Study of Proteasome Inhibitor Bortezomib
in Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma. J Clin
Oncol. 2004 Dec 21; PMID:
15613697
|
|
Phase II Clinical Experience With the Novel
Proteasome Inhibitor Bortezomib [Velcade] in Patients With
Indolent Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma. J Clin
Oncol. 2004 Dec 21; PMID:
15613699
|
| Marked clinical activity of the novel proteasome inhibitor bortezomib in patients with relapsed follicular (RL) and mantle cell lymphoma
(MCL). ASCO
2004 Abstract No: 6582
|
| Promising
Activity of the Proteasome Inhibitor Bortezomib (Velcade) in the
Treatment of Indolent Non-Hodgkin s
Lymphoma and Mantle Cell Lymphoma ASH
2003
|
| Velcade - Full prescribing info PDF
|
| Millennium says anti-cancer proteasome inhibitor safe over
longer term ASCO
|
| FDA
Approves Velcade (PS-341) for Multiple Myeloma Treatment FDA.gov
|
| Proteasome:
A New Target for Novel Drug Therapies Medscape
(free login req.)
|
| Proteasome inhibitors in the treatment of
B-cell malignancies.
Clin Lymphoma. 2002 Jun;3(1):49-55. PMID: 12141956 PubMed
|
| Full
prescribing information - millennium PDF
|
|
|
|
Radio-labeled
antibodies
Type: targeted immunotherapy / radiation
|
Antibodies
deliver targeted radiation to cancer cells, and reduces exposure to
normal cells. Bone marrow toxicity is common.
|
Telomerase
as an antigen
Type: biologic / molecular
|
Approved for other uses. Early testing for NHL)
Earlier study
"demonstrated that the RNA encoding the catalytic reverse transcriptase protein
component of human telomerase (hTERT RNA), when introduced into dendritic cells, can
stimulate the immune system to produce cytotoxic T lymphocytes (CTLs, or killer-T cells)
capable of recognizing and destroying telomerase-positive cancer cells." (Lymphomas
are among cancers in this category.)
| Treatment target: Telomere length correlates with
histopathogenesis according to the germinal center in mature B-cell
lymphoproliferative disorders. Blood. 2004 Jun 15;103(12):4644-9.
Epub 2004 Feb 26. PMID: 14988160
|
| Telomerase
inhibition with an oligonucleotide telomerase template antagonist:
in vitro and in vivo studies in multiple myeloma and lymphoma.
Blood. 2003 Sep 11 [Epub ahead of print] PMID:
12969977 | Related
|
| Telomeres
and telomerase in hematologic neoplasia. Oncogene. 2002 Jan
21;21(4):680-7. Review. PMID: 11850796 PubMed
|
|
|
|
Thalidomide
Type: biologic / immunotherapy / antiangiogenic
|
Approved for other uses. So far best activity seen for myeloma.
| Thalidomide for patients with recurrent
lymphoma.Cancer. 2004 Mar 15;100(6):1186-9. PMID: 15022285
|
|
|
|
Type: biologic
|
Inhibits enzyme
that changes the degree of supercoiling in DNA by cutting
one or both strands.
| Irinotecan in Relapsed or Refractory Non-Hodgkin’s Lymphomas, Vol 16, No 8, Suppl 7
(August 2002) cancernetwork.com
|
| DX-8951f: A new water-soluble
camptothecin derivative, DX-8951f, exhibits potent antitumor
activity against human tumors in vitro and in vivo. Jpn J Cancer
Res. 1995 Aug;86(8):776-82. abstract
| MSKCC
study
|
|
|
|
Motexafin gadolinium (MGd)
Topic
Search: PubMed
|
"Motexafin gadolinium (MGd)
belongs to a class of compounds known as texaphyrins, which are
expanded porphyrin macromolecules capable of forming complexes with
large cations such as lanthanides.
In tumor cells, MGd generates
reactive oxygen species (ROS) by accepting electrons from cellular
reducing metabolites and transferring them to oxygen. This results
in disruption of cellular metabolism and predisposes the tumor cell
to apoptosis when an additional stressor, such as radiation or
chemotherapy, is applied (11,
12).
Moreover, elegant tumor-specificity
and intracellular localization of MGd has been demonstrated by
DeStasio et al. and Woodburn et al. (11,
13).
The precise mechanisms for this tumor specificity are not well
identified. In other clinical trials, such as the one reported by
Carde et al. (14),
MGd has been shown not only to be tumor specific, but also
long-lived with tumor retention periods of weeks to months. Data
from UCLA by Ford et al., suggest that this retention and
consequential “enhancement” on T1 MRI is a function
of the dose of MGd (15)."
|
Zalypsis®
(Renieramycins)
Topic
Search: PubMed
|
Zalypsis® is a novel chemical entity related to the marine natural compounds Jorumycin and the family of
Renieramycins, obtained from molluscs and sponges, respectively. Zalypsis binds to DNA and is cytotoxic; however, it does not activate the “DNA damage checkpoint” response. Thus, Zalypsis has cytotoxic effects dependent on DNA binding that are not associated with DNA damage.
- pharmamar.com
Clinical trial for lymphoma: clinicaltrials.gov
NCT00359294 |
|
