Discovery in fight against bowel cancer

New research has discovered how a genomic approach to understanding bowel (colorectal) cancer could improve the prognosis and quality of life for patients.

Bowel cancer is the fourth most common cancer in the UK, with 41,200 people newly diagnosed each year. A number of treatment options are available but mortality rates remain high, with bowel cancer the second most common cause of cancer death in the UK.

Researchers at Queen’s University Belfast, in collaboration with the University of Oxford and the University of Leeds have made a significant advance in the treatment of bowel cancer. The study, which has been published in the journal Nature Communications, has shown how defining precise gene signatures within bowel cancer cells can allow us to develop novel prognostic and predictive markers for bowel cancer and help to drive personalised medicine approaches.

Full story via ScienceDaily

Link to the research:  Dunne, P.D. et al. Cancer-cell intrinsic gene expression signatures overcome intratumoural heterogeneity bias in colorectal cancer patient classification. Nature Communications, 2017

Advertisements

Precision medicine trial first of its kind to show benefit to patients

ScienceDaily | Published online: September 23 2016

target-454197_960_720

A clinical trial for types of advanced cancer is the first of its kind to show that precision medicine — or tailoring treatment for individual people — can slow down the time it takes for a tumor to grow back, according to research presented at the Molecular Analysis for Personalized Therapy (MAP) conference.

Results from the trial, which took place at the Gustave Roussy Cancer Campus in Paris, found that 199 out of 1110 patients with advanced cancer, who had their genes mapped and their treatment tailored, had around 30 per cent longer before their cancer started growing again compared to any of the previous therapies the patients had tried. This ranged from between five and 32 months.

This trial involved patients who had no other treatment options left and who had already tried three or more cancer therapies. The team found potential faulty molecules to target for 411 of these patients and experimental drugs to hit the targets for 199 of these patients.

Read the full commentary here

Pancreatic cancer resists personalized medicine: What researchers are doing to fight back

ScienceDaily. Published online: 4 August 2016

B0007659 Pancreatic cancer cells

Image source: Anne Weston, LRI, CRUK – Wellcome Images // CC BY-NC-ND 4.0

Image shows false colour scanning electron micrograph of pancreatic cancers cells grown in culture.

Researchers are taking a new, patient-directed approach to treating pancreatic cancer. Rather than relying on conventional cell lines that have defined effective drug targets for other types of cancers, they are creating and sequencing cell lines from a cancer patient’s own tissue. Their results reveal that pancreatic tumors are more varied than previously thought and that drug sensitivity is unique to each patient.

In the study, the team turned to a library of cancer drugs, representative of what’s available to patients, and tested each individually against a panel of different cell lines: either conventional pancreatic cell lines, which are often used by researchers and pharmaceuticals, or cell lines that the team developed directly from cancer patients. While conventional pancreatic cell lines were more sensitive to standard drugs used in pancreatic cancer treatment, cell lines from patients were not, with only a “handful” responding to any single-agent treatment.

Read the full commentary here

Read the research abstract here

Relevance of internal time and circadian robustness for cancer patients

Ortiz-Tudela, E. et al. BMC Cancer2016. 16:285

Background: Adequate circadian timing of cancer treatment schedules (chronotherapy) can enhance tolerance and efficacy several-fold in experimental and clinical situations. However, the optimal timing varies according to sex, genetic background and lifestyle. Here, we compute the individual phase of the Circadian Timing System to decipher the internal timing of each patient and find the optimal treatment timing.

Methods: Twenty-four patients (11 male; 13 female), aged 36 to 77 years, with advanced or metastatic gastro-intestinal cancer were recruited. Inner wrist surface Temperature, arm Activity and Position (TAP) were recorded every 10 min for 12 days, divided into three 4-day spans before, during and after a course of a set chronotherapy schedule. Pertinent indexes, I < O and a new biomarker, DI (degree of temporal internal order maintenance), were computed for each patient and period.

Results: Three circadian rhythms and the TAP rhythm grew less stable and more fragmented in response to treatment. Furthermore, large inter- and intra-individual changes were found for T, A, P and TAP patterns, with phase differences of up to 12 hours among patients. A moderate perturbation of temporal internal order was observed, but the administration of fixed chronomodulated chemotherapy partially resynchronized temperature and activity rhythms by the end of the study.

Conclusions: The integrated variable TAP, together with the asynchrony among rhythms revealed by the new biomarker DI, would help in the personalization of cancer chronotherapy, taking into account individual circadian phase markers.

Read the full article here

Cancer tumour genetics reveal possible treatment revolution

Ian Sample. The Guardian Healthcare. Published online: 4th March 2016.

A landmark discovery into the genetic makeup of tumours has the potential to open a new front in the war on cancer, delivering potent therapies that are tailored to individual patients, scientists have said.

The breakthrough comes from research into the genetic complexity of lung and skin cancers which found that even as tumours grow and spread around the body, they carry with them a number of biological “flags” that the immune system can be primed to attack.

Because the flags, which appear as surface proteins, are found only on cancer cells, they provide what scientists described as “exquisite targets” for new therapies that draw on the power of the immune system to combat cancer.

Treatments that harness the immune system have shown great promise against some forms of cancer, such as melanoma, but they do not work in everyone. One approach releases the brakes on the immune system, unleashing the full force of killer T cells, which are otherwise dampened down by cancer cells. But to work, the patient’s immune system must first recognise the cancer as the enemy.

Read the full news article here

New precision medicine guidelines aimed at improving personalized cancer treatment plans

A committee of national experts, led by a Cleveland Clinic researcher, has established first-of-its-kind guidelines to promote more accurate and individualized cancer predictions, guiding more precise treatment and leading to improved patient survival rates and outcomes.

These new guidelines are changing the traditional approach of cancer staging methods for cancer treatment. The new risk calculators — which will complement the existing staging system — will enable physicians to more accurately and precisely determine the best treatment for individual patients.

cancer_stages

Image source: simplyanon

The current cancer staging system (stages I-IV), otherwise known as TNM, has been used for decades and is a simple way to universally assess cancer progression in patients around the world. However, many believe that the system is outdated, lumping all cancer patients into 4 stages, which do not account for individual differences in risk factors–such as genetics, age, gender, and lifestyle. As a result, a patient who is, for example, a “bad” stage 3, might be undertreated for a cancer that is likely to metastasize. On the other hand, a “good” stage 3 patient might receive more aggressive treatment than is necessary, which can lead to toxic side effects on the heart, kidneys or other organs.

Now that the guidelines have been established, researchers across the world will be invited to submit their cancer risk formulas for review by AJCC, with the potential of changing the face of cancer treatment for millions of people worldwide.

Read the full commentary via ScienceDirect

Read the full article via CA: A Cancer Journal for Clinicians

Is It Finally Time for a Personalized Medicine Approach for Fluorouracil-Based Therapies?

Steven M. Offer, S.M. & Diasio, R.B. JCO: January 20, 2016 vol. 34no. 3 205-207

1583637033_a2240e2fbd_z.jpg

Image source: Derek K. Miller

At present, implementation of pretreatment genotypic tests to individualize fluorouracil (5-FU)-based chemotherapy is limited despite a wealth of evidence demonstrating that individuals who carry certain variants of the dihydropyrimidine dehydrogenase (DPD) gene (DPYD) are at significantly greater risk of experiencing severe and potentially lethal adverse toxicity (grade ≥ 3) when receiving treatment with standard dosages of 5-FU. The DPYD *2A variant—also known as rs3918290, NM_000110.3:c.1905+1G>A, and DPYD:IVS14_1G>A—has been reproducibly shown to result in a catalytic inactive form of DPD using a variety of methods, including the study of patient-derived clinical specimens1 and through direct in vitro study of the variant form of the protein.2 Despite strong evidence linking this variant to toxicity, and the mounting evidence linking additional DPYD variants to toxicity, the US Food and Drug Administration and the European Medicines Agency do not currently require pharmacogenomics testing before 5-FU administration.3 Both agencies, however, do recommend the use of alternative drugs in individuals with known DPD deficiency. Scientific groups, such as the Clinical Pharmacogenetics Implementation Consortium and the Dutch Pharmacogenetics Working Group, provide regularly updated gene and drug clinical practice guidelines to help to translate research results into actionable treatment decisions for various drugs, including 5-FU, on the basis of peer-reviewed pharmacogenetic information.46

Much of the information from these groups is disseminated by the Pharmacogenomics Knowledgebase, an actively updated, online resource for dosing guidelines, drug labels, and potentially actionable gene-drug and genotype-phenotype relationships.7However, it should be noted that the goal of these groups and online tools is not to direct which tests should be ordered, but, rather, to assist with the integration of test results into the decision-making process.

Carry on reading via JCO