Cu466 Analysis

This drug works by damaging the DNA in cancer cells and stopping them from multiplying. It binds together the strands of DNA so that cells can’t grow and divide (Cancer Research UK, 2015).

A team from the Brazilian university says the experimental drug binds with tumor cells and causes the loss of key molecules.

Abstract Cancer “Sucks” and many individuals today are dealing with it or know someone who has dealt with it. The late president Richard Nixon declared war on cancer in 1971 and we have been fighting the battle ever since (McCarthy, 2015, paras. 16). Since the declaration many possible cures were developed and chemotherapy is the one which seems to work on almost every cancer. However, this treatment has drawbacks that are either controversial or questionable as to what degree they help with defeating cancer.

During my time in the Brugge Lab, we have utilized our compound screening platform to examine vulnerabilities of cancer cells under therapeutic, environmental, and

The antitumor efficacy of crizotinib was dose dependent and demonstrated a strong correlation to inhibition of c-Met phosphorylation. Near-maximal inhibition of c-Met activity for the full dosing interval was necessary to maximize the efficacy of crizotinib [1].

In the past, most of the cancer drugs were developed to hinder the growth of tumors. The main strategy was so called “targeted therapies, which interfere with genetic signals that act like accelerators, causing tumors to grow.”1 However, because there are too many pathways and signals that can act as an accelerator of the cancer growth, a single drug was usually not enough to suppress the cancer.

Melanoma is a skin cancer derived from melanocytes and is considered to be the most common fatal malignancy of young adults. About 60% of melanomas harbor a mutation in BRAF, a serine/threonine protein kinase involved in promoting MAPK signaling and cellular proliferation. Of these, 90% harbor the BRAFV600E mutation. To combat this disease, the BRAF inhibitor, vemurafenib, was approved in 2011 to treat late-stage melanomas that are driven by the BRAFV600E mutation. Despite the immediate, positive clinical response to the drug, resistance develops after 7 months of vemurafenib treatment. Significant research effort has been devoted to understanding the origin of this drug resistance, but few studies have examined the fate of individual cells

The direct binding of rituximab to CD20 can trigger low-level apoptosis of tumor cells.6 Alterations in the apoptotic pathway signaling could therefore lead to cells becoming resistant to rituximab. Rituximab-resistant cell lines have been produced through repeated exposure to the antibody. These cell lines show apoptosis resistance and lack sensitivity to multiple cytotoxic chemotherapeutic agents, including rituximab. Numerous variations of pro- and anti-apoptotic regulators in these rituximab-resistant cell lines have been described.12 The nuclear factor-kappaB (NFkB) pathway is specifically overactivated, leading to increased expression of anti-apoptotic proteins from the Bcl-2 family. These clones can then be resensitized to rituximab by simply exposing them to inhibitors of these survival pathways in

Methotrexate is an antimetabolite of folic acid that blocks the formation of thymine within the cell, rendering it incapable of DNA replication. As a chemotherapeutic agent, it is also employed as an alternative treatment for psoriasis and rheumatoid arthritis when they are unresponsive to conventional therapies. Methotrexate (MTX) induces an effect similar to 5-fluorouracil (5-FU) by interrupting the formation of thymine within the cell, which leads to the inability to replicate DNA. Unlike 5-FU, which inhibits the action of thymidylate synthetase, MTX binds tightly to dihydrofolate reductase (DHFR) and blocks the formation of tetrahydrofolate, leading to the depletion of associated folate co-factors (126).

Even though BCC is genetically different from other types of cancers due to its inability to metastasize, the identification of these new drivers can offer a starting point for other researchers to investigate the potential drivers in other forms of cancer that are more complex and have genomic instability. In some ways, BCC has already begun being compared to cancers such as colorectal cancer and pancreatic cancer. Preclinical studies demonstrated the antitumor activity of vismodegib in xenograph models of colorectal and pancreatic cancer. Similarly, phase 1 clinical trials in advanced BCC highlighted an objective response to vismodegib (De Smaele et al.). Due to vismodegib’s low toxicity and specificity for the Hh pathway, this drug has potential advantages compared with conventional chemotherapy, and may eventually be used in combination

The p53 protein’s primary function is to protect an organism against proliferation of cells containing damaged DNA, this is done in several ways, including cell cycle arrest and apoptosis.43, 44 MDM2 has been shown to be the principal negative regulator of p53, inhibiting its tumour suppressing abilities and thus leading to tumour propagation. To this end disruption of the MDM2/p53 interface is an attractive strategy in cancer therapeutics.45, 46 Independently Grasberger and Vassilev both successfully used HTS of large compound libraries to discover small molecule inhibitors of MDM2.47, 48 Grasberger’s benzodiazepinedione and Vassilev’s cis-imidazoline (Nutlin) were both able to bind to MDM2 at the MDM2/p53 binding region, disrupting the interface and thus blocking the interaction. Subsequent medicinal chemistry optimisation of the Nutlin molecule class (3) yielded the drug compound RG7112 (4, Figure 4).49 RG7112 has been subject to several exploratory human trials showing favourable outcomes, inducing apoptosis and decreasing tumour proliferation in patients with leukaemia and various other

AMG 925 is an effective and orally bioavailable dual inhibitor of FLT3 and CDK4. AMG 925 inhibits the proliferation of a batch of human tumor cell lines including Colo205 (Rb+) and U937 (FLT3WT) cells. AMG 925 also induced apoptosis in FLT3 mutant AML cells, including MOLM13 (FLT3ITD) and MOLM13 (FLT3ITD, D835Y)

NAD(P)H quinone-acceptor oxidoreductase (NQO1) is an enzyme that is responsible for reducing quinones to hydroquinones in the cell. This minimizes the generation of reactive oxygen intermediates by redox cycling and also depletes the intracellular thiol pool. NQO1 consists of 2 catalytic sites which uses NAD(P)H as an electron donor in order to form hydroquinones. The metabolic activation of a variety of quinone-based anticancer agents occurs, in part, as a result of the bioreductive activation by NQO1. Its association with p53 gene results in proteosomal degradation in the nucleus, thereby broadening the cyto-protective role far beyond

Decitabine is a DNMT inhibitor utilized in the treatment of myelodysplastic syndrome and acute myeloid leukemia. It is a nucleoside analogue. It was formerly used in large doses as a cancer treatment and was found to not only be ineffective in treating cancer but had numerous, intolerable side effects. However, more recently it has been used in much smaller doses with excellent results. The smaller doses are sufficient to allow binding to DNMT after its inclusion in DNA. It disrupts the methylation of DNA elements, allowing the tumor suppressor genes to function normally. Its effects depend on cell replication which is, of course, a primary characteristic of cancer cells. Thus it is more disruptive to cancer cells than to normal cells.

Genomic heterogeneity and its effects on cancer therapeutic agents are very important, So that genotype differences potentially establish a necessary basis for sensitivity of drug differences between established cancer cell lines and primary tumor cells.