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PhD Position – KRAS Tumor Heterogeneity, Clinical Medicine – Aarhus, Denmark Jan 2022

Aarhus University (AU), Denmark

Aarhus University invites applications for a Ph.D. Position – aim of this project is to investigate the extent of KRAS tumor heterogeneity, and any KRAS negative subclones in patients with detected KRAS G12C mutation, at the Department of Clinical Medicine, Denmark – Jan 2022

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General Info

Position: PhD Position
No. of Positions: 1
Research Field:
Deadline to Apply: Expired
Joining Date: Feb 01, 2022
Contract Period: -
Salary: According to Standard Norms

Workplace:
Department of Clinical Science
Aarhus University
Aarhus University (AU)

Aarhus C, ,

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Qualification Details

The applicant must have practical and theoretical experience with in situ techniques in relation to histological specimens. Futhermore, the applicant must have some experience in extraction of DNA from formalin fixed and parrafin embedded tissue samples and knowledge of sequencing techniques. Applicants with one or several publications in relation to the above mentioned techniques will be prefered.

Responsibilities/Job Description

KRAS mutations and Tumor heterogeneity in lung and lower intestinal cancer. Significance for treatment response

Call for applications for a fully financed PhD project.

The aim of this project is to investigate the extent of KRAS tumor heterogeneity, and any KRAS negative subclones in patients with detected KRAS G12C mutation. We will investigate the precense of KRAS negative subclones, in both primary tumor and metastases, as well as in any recurrences in patients with NSCLC and colorectal cancer.

The results of the in situ techniques will be confirmed by selecting positive and negative subclones for next generation sequencing.

How to Apply?

Online Application through "Apply Now" Button from this page

Reference Number: -
(If any, use it in the necessary place)

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Documents Required

Please submit your application via this link. Application deadline is 20 January 2022 23:59 CET. Preferred starting date is 1 February 2022.

For information about application requirements and mandatory attachments, please see our application guide

About the Project

KRAS mutations are a crucial “driver” in 90% of ductal pancreatic adenocarcinomas, in 40% of colorectal carcinomas and in 30% of non-small cell lung cancer (NSCLC). Until recently, there have been no effective treatments targeting KRAS mutations. The Food and Drug Administration (FDA) have just approved the first KRAS-blocking drug (Sotorasib, AMGEN, USA) for the treatment of patients with locally advanced or metastatic NSCLC. The approval only covers patients with the KRAS G12C mutation who have received at least one other systemic cancer treatment such as chemotherapy.

The approval of Sotorasib is based on the results of a study involving 124 people with KRAS G12C mutated NSCLC who had previously received other treatments. Objective response was found in 46 patients (37%). This is in contrast to standard treatments, where an objective response is observed in less than 20% of patients with NSCLC. Although the results are promising, only a proportion of patients show response to targeted treatments against activating mutations / translocations and the response is often of shorter duration.

There are several explanations for the disappointing response. The detected mutation is not the primary driver for the cancer cells, the blockade of the detected driver mutation is bypassed by the cancer cell as other signaling pathways take over, resistance mutations occur in the primary driver, or tumor heterogeneity. Tumor heterogeneity may have a significant impact on the treatment efficiency.

In situ techniques, such as hybridization and immunohistochemistry (IHC) on tissue specimens (histological samples), are effective ways to test for subclones with probes against the mRNA for the mutated gene or a well-functioning antibody against the protein of the mutated gene.

About the Employer:

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Contact details

Please contact Professor Torben Steiniche, steiniche@clin.au.dk, for further information.

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