SEARCH · PubMed Health

Results for “molecular profiling”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources

PubMed2026

Targeted Therapy in Acute Myeloid Leukemia: Current Approaches and Novel Directions.

Acute myeloid leukemia (AML) is a molecularly heterogeneous neoplasm of hematopoietic stem and progenitor cells. The advent of high-resolution genomic sequencing has uncovered several genetic drivers of AML which spurred a surge of therapies that target the disease at a mutational, clonal, or epigenetic level. Currently, the molecular profiling of AML patients before treatment is commonplace and crucial for ensuring that patients receive the most optimal therapy for any driver mutations they may have. Here, we detail the current targeted therapies available for AML: specifically, those targeting the BCL2 family (venetoclax), FLT3 (midostaurin, gilteritinib, quizartinib), IDH1/2 (enasidenib, ivosidenib), and MENIN (revumenib, ziftomenib). In addition, we outline potential mechanisms of resistance against these therapies, as well as efforts being taken to prevent or bypass them.

BCL2↗

PubMed2005

Comparison of cryopreservation and standard needle biopsy for gene expression profiling of human breast cancer specimens.

Given the growing importance of molecular profiling of breast cancer, we initiated a small study to test whether human breast biopsies obtained via cryopreservation large core needle biopsy (C-LCNB) provided similar gene expression profiles compared with 'optimally handled' standard large core needle biopsy (S-LCNB) specimens. Five matched pairs of C-LCNB versus S-LCNB were obtained at the same visit, and subjected to gene array expression analysis using the Affymetrix system with U133A chips. No significant changes in gene expression were identified comparing the C-LCNB versus the matched S-LCNB from individual patients. This was corroborated by a paired t-test analysis, which supported the hypothesis that the S/C biopsies measured equivalent samples. A small number of genes (17) showed decreased expression when second biopsies were compared with first biopsies, suggesting a slight patient response to the first biopsy. A scatter plot analysis comparing first biopsy versus second biopsy values disclosed a slope of 0.859, further indicating that the first biopsy affects the second biopsy measurement. It therefore appears that conventional biopsies, when handled appropriately, provide RNA which is equivalent to RNA from biopsies which are frozen immediately, but that multiple biopsy protocols may introduce additional complexities.

Biopsy, Needle↗

PubMed1986

Release and characterization of cholecystokinin from isolated canine jejunal cells.

We have developed an isolated intestinal cell system to study the regulation of cholecystokinin release. Enzymatically dispersed canine jejunal mucosal cells were separated by counterflow elutriation to enrich cholecystokinin content 20-fold. Release of cholecystokinin from freshly isolated cells was determined by radioimmunoassay. Elevated extracellular potassium, dibutyryl cyclic adenosine monophosphate, and the diterpene derivative forskolin each stimulated an increase in cholecystokinin release over a 60-min period compared to basal secretion. L-Tryptophan stimulated a dose-dependent and stereospecific increase in cholecystokinin. D-Tryptophan did not significantly alter basal cholecystokinin secretion. Carbachol inhibited L-tryptophan-stimulated cholecystokinin release in a dose-dependent manner. Analysis of extracts from intact jejunal mucosa by high-pressure liquid chromatography revealed three components with cholecystokinin immunoreactivity eluting in positions with cholecystokinin 8, with cholecystokinin 33/39, and after cholecystokinin 33/39. Only the two molecular forms coeluting, respectively, with cholecystokinin 8 and cholecystokinin 33/39 were present in the elutriator-enriched jejunal cells, and these two forms of cholecystokinin immunoreactivity were released from cells upon stimulation. These data suggest that L-tryptophan directly regulates the release of cholecystokinin and that membrane depolarization and intracellular generation of cyclic adenosine monophosphate may play a role in activating cholecystokinin cells. Stimulated cholecystokinin release is inhibited by the muscarinic agonist carbachol. The molecular profile of released cholecystokinin corresponded to the two molecular components, cholecystokinin 8 and cholecystokinin 33/39, contained in dispersed cells.

Animals↗

PubMed2005

DNA microarrays in clinical cancer research.

The recent sequencing of the human genome, coupled with advances in biotechnology, is enabling the comprehensive molecular "profiling" of human tissues. In particular, DNA microarrays are powerful tools for obtaining global views of human tumor gene expression. Complex information from tumor "expression profiling" studies can, in turn, be used to create novel molecular cancer diagnostics. We discuss the utility of DNA microarray-based tumor profiling in clinical cancer research, highlight some important recent studies, and identify future avenues of research in this evolving field.

Biomarkers, Tumor↗

PubMed1993

Pharmacological profile of reviparin-sodium.

Clivarin (reviparin-sodium) is a homogeneous low molecular weight heparin (LMWH) as determined by the data obtained in molecular profiling studies. The limited biochemical studies carried out indicate that this LMWH has a specific potency of 124 anti-XA IU/mg and a weaker aPTT activity of approximately 30 U/mg. Assay-dependent neutralization of the in vitro effects of reviparin-sodium were noted. Protamine preparations at equigravimetric concentrations effectively neutralized the aPTT and TT effects; however, Heptest and anti-Xa effects were only partially neutralized. In contrast, heparin's effects were completely neutralized by this agent. PF 4 only partially neutralized the effects of reviparin-sodium. Assay-dependent variations were noted in this study. In comparison with heparin, the haemorrhagic effects of reviparin-sodium were much weaker. Reviparin-sodium produced a dose-dependent antithrombotic action in both the intravenous and subcutaneous studies. This agent also showed sustained activity and better bioavailability characteristics than heparin. Reviparin-sodium exhibited a distinct biochemical and pharmacological profile that may be useful in the optimization of LMWH.

Animals↗

PubMed2026

Somatic genetic alterations in pituitary neuroendocrine tumors.

The molecular characterization of pituitary neuroendocrine tumors (PitNETs) has progressed pronouncedly in recent years, unraveling the molecular pathways driving initiation and progression of different PitNET types and allowing a better understanding of their biology. The most frequent recurring somatic driver alterations were recognized in corticotroph PitNETs (USP8, USP48, BRAF) and somatotroph PitNETs (GNAS) and, much less frequently, in lactotroph PitNETs (SF3B1). Additional well-characterized somatic driver alterations, including TP53, ATRX, and DAXX, are enriched in aggressive corticotroph tumors. Identification of new molecular markers and delineation of their clinical phenotypes are enabling further subclassification of PitNETs based on tumor molecular profiles, with earlier recognition of more aggressive variants. These molecular markers also provide an opportunity for new targeted therapies. Beyond single-gene alterations, epigenetic modifications, such as DNA methylation, histone modifications, and noncoding RNA dysregulation, are emerging as important contributors to PitNET pathogenesis and potential therapeutic targets. Multi-omics approaches encompassing genomics, transcriptomics, epigenomics, and proteomics are transforming PitNET classification. In this review, we provide a comprehensive, data-driven update on somatic driver alterations, epigenetic alterations, converging signaling pathways, and the related emerging therapeutic targets in PitNETs, integrating pooled analyses from published cohorts.

Humans↗

PubMed2006

Whole transcriptome amplification for gene expression profiling and development of molecular archives.

Expression profiling of clinically obtainable tumor specimens has been hindered by the need for microgram quantities of RNA. In vitro transcription (IVT)-based amplifications are most commonly used to amplify small quantities of RNA for microarray analysis. However, significant drawbacks exist with IVT-based amplification, and the need for alternative amplification methods remains. Herein, we validate whole transcriptome amplification (WTA), an exponential amplification technique that produces cDNA libraries and amplified target in 3 to 4 hours from nanogram quantities of total RNA using a combination of cDNA microarrays and quantitative polymerase chain reaction (PCR). We demonstrate that WTA material can serve as a "molecular archive" because a WTA cDNA library can be faithfully amplified through multiple rounds of PCR amplification, allowing it to serve as a bankable and distributable resource. To demonstrate applicability, WTA was combined with laser capture microdissection to profile frozen prostate tissues. Unlike most IVT-based and exponential amplification techniques, WTA does not depend on the presence of a poly-A tail. Thus, we demonstrate that WTA is compatible with artificially degraded RNA and RNA isolated from formalin-fixed paraffin-embedded tissues. Taken together, WTA represents a versatile approach to profile and archive cDNA from minute tumor samples and is compatible with partially degraded RNA.

Biological Specimen Banks↗

PubMed2000

Gene expression profile in mouse myocardium after ischemia.

This study was designed to elaborate a molecular profile of expressed genes during ischemic injury to the mouse heart after surgical constriction of the left coronary artery without reperfusion. A mouse cDNA array containing 588 known genes was used to compare gene expression in heart RNA after 24-h ischemia with control tissue. Alterations in gene expression on the array were supported by relative reverse transcription-polymerase chain reaction analysis after timed periods of ischemia. Decreased levels of the cell cycle regulator p18ink4 and the oxidative responsive gene glutathione S-transferase were accompanied by an upregulation of the genes associated with cardiac muscle development, alpha-myosin heavy chain and fetal myosin alkali light chain. Other stress responses elicited by cardiac injury included an induction of Egr-1 and Egr-3 transcription factors, as well as the apoptotic regulator Bax. Altogether, these findings indicate that expression of genes associated with a fetal transcription program may be involved with the post ischemic remodeling process in heart ventricles.

Animals↗

PubMed1997

Fast and slow skeletal muscles express a common basic profile of acetylcholinesterase molecular forms.

Recent evidence suggests that the high content of acetylcholinesterase (AChE) globular form G4, characteristic of fast muscles, is controlled by phasic high-frequency activity performed by these muscles. This indicates that inactive, though still innervated, fast muscles should be devoid of their characteristic G4 pool. Accordingly, in the absence of phasic activity, both fast and slow muscles should exhibit a common basic profile of AChE molecular forms of the slow type. We first tested this hypothesis by examining the AChE content in cultures of myotubes obtained from the fusion of satellite cells originating from fast and slow muscles. These two cell populations produced AChE molecular-form profiles of the slow type characterized by modest levels of G4 together with an increased proportion of the asymmetric forms A8 relative to A12. Second, we determined the impact of muscle paralysis on the specific content of AChE molecular forms of adult rat fast and slow muscles. Complete paralysis of hindlimb muscles was achieved by chronic superfusion of tetrodotoxin (TTX) onto the sciatic nerve. Ten days after TTX inactivation, the distributions of AChE molecular forms of both fast extensor digitorum longus (EDL) and plantaris muscles were transformed into ones resembling the slow soleus, the latter showing no significant modifications in its AChE profile. Finally, we investigated the impact of nerve-mediated phasic high-frequency stimulation of TTX-inactivated fast and slow muscles on the content of AChE molecular forms. This stimulation produced a profile of AChE molecular forms similar to that observed in control EDL muscles, indicating that phasic activation counteracted the TTX-induced transformation in the distribution of AChE molecular forms in fast EDL muscles. Together, these results are consistent with the proposal that adult fast muscles constitutively express a basic profile of AChE molecular forms of the type displayed by slow muscles, onto which varying levels of G4 are added according to the amount of phasic activity performed by the muscles.

Acetylcholinesterase↗

PubMed2026

Integrated expression profiling of trophoblast cell-surface antigen 2 (TROP2), folate receptor alpha (FRα), and human epidermal growth factor receptor 2 (HER2) in endometrial Cancer across molecular classes, genomic alterations, and histologic subtypes.

OBJECTIVE: Antibody-drug conjugates (ADCs) are expanding treatment options in endometrial carcinoma, but the distribution of actionable surface targets across histologic, molecular, and genomic subgroups remains incompletely defined. METHODS: This single-institution retrospective tissue microarray (TMA) study included 312 endometrial carcinomas: 158 endometrioid and 154 serous tumors. Trophoblast cell-surface antigen 2 (TROP2) was quantified by histochemical score (H-score); human epidermal growth factor receptor 2 (HER2) was assessed using endometrial carcinoma-specific and gastric/DESTINY-PanTumor02 criteria; and folate receptor alpha (FRα) positivity was defined as ≥75% viable tumor cells with ≥2+ membranous staining. Molecular class was assigned using a hierarchical DNA polymerase epsilon (POLE)-mutant, microsatellite instability/mismatch repair-deficient (MSI/MMRd), p53-abnormal, and no specific molecular profile (NSMP) classifier. Tumor mutational burden (TMB) and recurrent genomic alterations were analyzed in relation to biomarker expression. RESULTS: TROP2 was broadly expressed, with median H-scores of 280 in endometrioid and 200 in serous carcinomas. HER2 gastric-score 2+/3+ expression and FRα positivity were enriched in serous versus endometrioid carcinoma (22.5% vs 8.9% and 20.1% vs 4.4%), restricted to FIGO grade 3 tumors, and concentrated in p53-abnormal disease. FRα positivity was absent in POLE-mutant and MSI/MMRd tumors. HER2 2+/3+ expression correlated with erb-b2 receptor tyrosine kinase 2 (ERBB2) alterations, whereas FRα-positive tumors were enriched for TP53 alterations and showed lower frequencies of ARID1A and PTEN alterations. Triple-negative TROP2/HER2/FRα tumors were uncommon (6/308, 1.9%). CONCLUSIONS: TROP2 is broadly expressed in endometrial carcinoma, whereas HER2 and FRα define a more restricted high-grade, serous/serous-like, p53-abnormal compartment, supporting biomarker-informed ADC development.

Humans↗

PubMed2006

High-throughput genomic technology in research and clinical management of breast cancer. Molecular signatures of progression from benign epithelium to metastatic breast cancer.

It is generally accepted that early detection of breast cancer has great impact on patient survival, emphasizing the importance of early diagnosis. In a widely recognized model of breast cancer development, tumor cells progress through chronological and well defined stages. However, the molecular basis of disease progression in breast cancer remains poorly understood. High-throughput molecular profiling techniques are excellent tools for the study of complex molecular alterations. By accurately mapping changes in the genome and subsequent biological/molecular pathways, the chances of finding potential novel treatment targets as well as intervention strategies are enhanced, and ultimately lives can be saved. This review provides a brief summary of recent progress in identifying molecular markers for invasiveness in early breast lesions.

Breast↗

PubMed2005

The epigenome as a molecular marker and target.

Tumor cell proliferation, de-differentiation, and progression depend on a complex combination of altered cell cycle regulation, excessive growth factor pathway activation, and decreased apoptosis. The understanding of these complex mechanisms should lead to the identification of potential molecular markers, targets, and molecular profiles that should eventually expand and improve therapeutic intervention. It now appears clear that methylation plays a central role in transformation, both in vitro and in vivo. However, the exact targets and mechanism(s) are not yet fully understood. This is partly due to the significant number of genes altered by changes in intracellular methyltransferase activity and the chemical agents used to modulate gene expression. The complex nature of methylation's role in regulating gene expression suggests that in addition to investigating individual genes, researchers should develop more comprehensive methods to examine gene expression patterns and their predictive value as this will likely be necessary in the future. If methylation plays a role in transformation, then it seems logical that genes regulating intracellular methylation status may be used as molecular markers to profile tumors by any new methods currently being developed. Perhaps more noteworthy is that DNMT genes may be found to be novel molecular targets for new factor-specific anticancer agents. This idea will be addressed.

Azacitidine↗

PubMed1999

Molecular genetic aspects of oligodendrogliomas including analysis by comparative genomic hybridization.

Oligodendroglial neoplasms are a subgroup of gliomas with distinctive morphological characteristics. In the present study we have evaluated a series of these tumors to define their molecular profiles and to determine whether there is a relationship between molecular genetic parameters and histological pattern in this tumor type. Loss of heterozygosity (LOH) for 1p and 19q was seen in 17/23 (74%) well-differentiated oligodendrogliomas, in 18/23 (83%) anaplastic oligodendrogliomas, and in 3/8 (38%) oligoastrocytomas grades II and III. LOH for 17p and/or mutations of the TP53 gene occurred in 14 of these 55 tumors. Only one of the 14 cases with 17p LOH/TP53 gene mutation also had LOH for 1p and 19q, and significant astrocytic elements were seen histologically in the majority of these 14 tumors. LOH for 9p and/or deletion of the CDKN2A gene occurred in 15 of these 55 tumors, and 11 of these cases were among the 24 (42%) anaplastic oligodendrogliomas. Comparative genomic hybridization (CGH) identified the majority of cases with 1p and 19q loss and, in addition, showed frequent loss of chromosomes 4, 14, 15, and 18. These findings demonstrate that oligodendroglial neoplasms usually have loss of 1p and 19q whereas astrocytomas of the progressive type frequently contain mutations of the TP53 gene, and that 9p loss and CDKN2A deletions are associated with progression from well-differentiated to anaplastic oligodendrogliomas.

Adolescent↗

PubMed2002

Molecular determinants of human uveal melanoma invasion and metastasis.

The molecular analysis of cancer has benefited tremendously from the sequencing of the human genome integrated with the science of bioinformatics. Microarray analysis technology has the potential to classify tumors based on the differential expression of genes. In the current study, a collaborative, multidisciplinary approach was utilized to study the molecular determinants of human uveal melanoma invasion and metastasis. Uveal melanoma is considered the most common primary intraocular cancer in adults, resulting in the death of approximately 50% of patients affected. Unfortunately, at the time of diagnosis, many patients already harbor microscopic metastases, thus underscoring a critical need to identify prognostic markers indicative of metastatic potential. The investigative strategy consisted of isolating highly invasive vs. poorly invasive uveal melanoma cells from a heterogeneous tumor derived from cells that had metastasized from the eye to the liver. The heterogeneous tissue explant MUM-2 led to the derivation of two clonal cell lines: MUM-2B and MUM-2C. Further morphological and functional analyses revealed that the MUM-2B cells were epithelioid, interconverted (expressing mesenchymal and epithelial phenotypes) highly invasive, and demonstrated vasculogenic mimicry. The MUM-2C cells were spindle-like, expressed only a vimentin mesenchymal phenotype, poorly invasive, and were incapable of vasculogenic mimicry. The molecular analysis of the MUM-2B vs. the MUM-2C clones resulted in the differential expression of 210 known genes. Overall, the molecular signature of the MUM-2B cells resembled that of multiple phenotypes--similar to a pluripotent, embryonic-like genotype. Validation of select genes that were upregulated and down-regulated was conducted by semiquantitative RT-PCR measurement. This study provides a molecular profile that will hopefully lead to the development of new molecular targets for therapeutic intervention and possible diagnostic markers to predict the clinical outcome of patients with uveal melanoma.

Adult↗

PubMed2005

Non-invasive neoplasia of the stomach.

Invasive gastric cancer is the final step of a cascade of genomic and phenotypic changes, which have been defined as multistep oncogenesis. This process includes a continuum of progressively dedifferentiated phenotypes, which may result in a biologically new (i.e., nuepsilonomega = neo) cell characterized by autonomous, potentially metastatic, growth (i.e., pilambdaalphazetaomega = plasia). The clinico-pathological characterization of the advanced gastric precancerous lesions has important implications for both primary and secondary cancer prevention. The WHO agency has recently redefined dysplasia as intraepithelial [i.e., non-invasive neoplasia (NiN)]; such a proposal is consistent with the biological profile of dysplasia, which shares with invasive cancer some significant molecular attributes. Long-term follow-up studies have demonstrated that, in the natural history of gastric cancer, NiN precedes invasive adenocarcinoma. In this review, the morphological features of gastric NiN are described, also illustrating differences and similarities between the current and the previously adopted histological diagnostic criteria. The molecular profile of NiN is summarized and the spectrum of the options in the clinical management of gastric NiN are reported.

Disease Progression↗

PubMed2026

Molecular and Immune Landscape of Recurrent and/or Distant Metastatic Squamous Cell Carcinoma of the Head and Neck: An EORTC/IMMUCAN Project.

PURPOSE: Recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) is a heterogeneous clinical entity with a poor prognosis. The molecular and immune landscape of R/M SCCHN is underexplored. To offer a comprehensive view of the tumor microenvironment and molecular profile of R/M SCCHN, we performed an in-depth molecular and immune characterization, evaluating the impact of human papillomavirus (HPV) status, tobacco and alcohol history, primary tumor site, relapse pattern, and treatment history at the genomic, transcriptomic, and immune levels. EXPERIMENTAL DESIGN: We analyzed 253 R/M SCCHN fresh tumor biopsies from the IMMUcan project using RNA sequencing (RNA-seq), whole-exome sequencing, and multiplex immunofluorescence (mIF). RESULTS: The primary clinical factor affecting the immune microenvironment was the number of treatment lines, with significant declines in T cells and B cells observed via mIF and RNA-seq as the number of R/M treatment lines progressed. IL6, IL13, IL15, and NRF2 pathways were enriched in HPV-negative R/M SCCHN compared with HPV-positive tumors, whereas no immune differences were detected between these two clinical groups. Specific genomic alterations were observed in laryngeal cancer (DDR2, FOXP1, KLF5, and ROBO2), whereas nonsmokers/nondrinkers exhibited alterations in SPEN, PBRM1, and CYLD. 11q13.3 amplification was linked to HPV-negative metastatic tumors and hypopharyngeal cancer. HPV-negative SCCHN with locoregional recurrence showed elevated EGFR and CXCL12 pathway activity. Partial epithelial-mesenchymal transition transcriptomic signatures correlated with poor survival, whereas lymphocyte infiltration, especially in the context of tertiary lymphoid structures, was associated with improved survival. CONCLUSIONS: Our study highlights key molecular and immune differences across R/M SCCHN subgroups, identifies potential biomarkers, and suggests biological rationales for tailored therapeutic strategies.

Humans↗

PubMed2006

Identification of genes linked to gefitinib treatment in prostate cancer cell lines with or without resistance to androgen: a clue to application of gefitinib to hormone-resistant prostate cancer.

Understanding the molecular action of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, might allow us to perform more effective therapies for hormone-independent advanced prostate cancer. A DNA microarray study was undertaken to comprehensively analyze the alteration of levels of 1,081 genes after gefitinib treatment in androgen-independent PC3 and DU145 cells and androgen-dependent LNCaP cells. The proliferation of PC3, DU145 and LNCaP cells was significantly inhibited by 50.2%, 83.8% and 55.2%, respectively, 6 days after 10 microM gefitinib administration. Of the above 1,081 genes, we identified 23, 13 and 33 genes with significantly different expression in PC3, DU145 and LNCaP cells, respectively, 24 h after 10 microM-gefitinib exposure. Among the identified genes, only Quiescin Q6, a negative cell cycle regulator, was increased after gefitinib treatment in all three cell lines regardless of gefitinib sensitivity. Except for Quiescin Q6, there were no overlapping genes between PC3 and DU145 cells. However, levels of several oncogenes or proliferation-related genes were changed after gefitinib treatment in the 2 androgen-independent cell lines. We also identified 7 unique genes [glycyl-tRNA synthetase, interferon, alpha-inducible protein, stratifin, nuclear factor of kappa light polypeptide gene enhancer in B-cells 1, dual specificity phosphatase 9, guanine nucleotide binding protein (G protein) beta polypeptide 2, neural retina leucine zipper] whose levels were altered exclusively after gefitinib administration in gefitinib-resistant PC3 and LNCaP cells, but not in DU145 cells, suggesting that these 7 genes could be targets for overcoming gefitinib resistance. Collectively, our molecular profiling data will serve as a framework for understanding the molecular action of gefitinib for prostate cancer.

Androgens↗

PubMed2006

Pharmacogenomics and colorectal cancer.

The current methods of treating cancer patients with chemotherapeutics do not account for interpatient variability in the expression of particular target genes. This variability leads to unpredictable tumor responses and host toxicity. The approach we have taken is to determine gene expression levels in the metabolic pathways of drugs used in the treatment of gastrointestinal tumors. One of the main obstacles in the evaluation and determination of these markers has been the limitations of available technology. Many advances have been made in the development of more sophisticated techniques and the ability to perform these techniques on paraffin-embedded tumor tissue. In fact, with the identification of genetic polymorphisms, these markers may be obtained from peripheral blood specimens, thus making access to tissues a moot issue. An immediate goal is the application of this nascent technology and incorporation of these data in prospective clinical trials that would stratify patients according to their molecular profile. The ability to predict with a high degree of accuracy which patients are likely to respond to treatment and identify those who are not likely to respond will significantly influence the design of new treatment regimens with fluoropyrimidines and platinum. Tumors with high TS, TP, and DPD expression levels should be treated with such non-TS-directed anticancer drugs as irinotecan or oxaliplatin, or in combination with 5-FU. Patients with high expression of ERCC1 should be treated with nonplatinum-based regimens, whereas patients with low levels would be good candidates for cisplatin or oxaliplatin. We now understand that molecular determinants play an important role in response to 5-FU. With the development of new effective anticancer drugs such as irinotecan and oxaliplatin, it is important to gain a better understanding about the metabolism of these new active agents and mechanisms of resistance. It is essential to understand why some patients develop life-threatening toxicity and why some tumors are resistant to irinotecan or oxaliplatin. With the integration of novel-targeted therapies such as Erbitux and Avastin, molecular characterization and profiling will become more important for patient selection. Preliminary data suggest that germ line polymorphisms of cyclin D and gene expression levels of VEGF are associated with efficacy of Erbitux therapy.

Antineoplastic Agents↗