Oncology Highlights - February 2019
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Enjoy reading! - The SMS-oncology team
In the process of aqcuiring ‘superpowers’ to gain immune evasion abilities and become immortal, cancer cells occasionally relinquish other skills which make them vulnerable. In rare cases, cancers lose the capability to make key nutrients, such as amino acid asparagine in certain types of leukemia. Researchers from Rockefeller University scanned for other cancer types that might be vulnerable to cut-offs in nutrient supply. They first looked at cholestrol as an essential ingredient for all dividing cells. Scanning 28 different cancer types in the absence of cholesterol for survival they identified a rare type of lymphoma, known as ALK-positive ALCL, which did not endure these conditions, suggesting that these cells could not synthesize cholesterol on their own. This cholestrol-dependent cancer type lacked the squalene monooxygenase enzyme that catalyzes the de-novo synthesis of cholestrol. These findings not only indicate novel ways to target ALCL cells, but also expand possibilities to identify and exploit other cancers with similar vulnerabilities. The study was published in Nature. (image source: shutterstock)
The National Cancer Institute (NCI) initiated a collaborative project named The Human Tumor Atlas Network (HTAN) that will map the spatiotemporal development of cancer while capturing the molecular features of tumor cells. Resembling an “atlas”, the HTAN project aims to provide oncologists with a guide that can predict the route that cancer might use to develop, spread, or respond to treatment. In this interactive map, the 3D location of individual cells in a tumor will be depicted and followed to understand how the molecular, cellular and spatial features of a tumor change as it progresses over time, as well under treatments. The HTAN project will also incorporate single-cell technologies to gain a “street-level view” and distinguish tumor cells and immune cells to understand the tumor microenvironment. DNA sequencing, RNA sequencing, epigenetic analysis, and identification of protein content will be employed to find biomarkers that can be utilized for stratification and early detection of cancer in patients. (Image source: NCI HTAN)
Barcoding sheds light on metastasis and treatment resistance in triple negative breast cancer (TNBC)
A technique called “barcoding” allows researchers to track the fate of individual cells over time. Researchers did just this to follow individual human Triple Negative Breast Cancer (TNBC) cells, which were implanted into mice, as they grew into a tumor and spread to the bloodstream and other parts of the animal. This technique identified two subsets of tumor cells: shedders and seeders. “Shedders” are cells that escape from the primary tumor and enter the bloodstream, while “seeders” are a deadly subset of shredder cells that can colonize distant organs. Surgical removal of the primary tumor reduced both the number of shedders and seeders, while systemic cisplatin chemotherapy treatment only temporarily reduced the size of the primary tumor, with little effect on the number of shedders or seeders after treatment. These findings, provide new insights on cancer relapse after chemotherapy, and provides a way to focus on the dangerous seeder cells that are responsible for metastasis. Understanding the unique changes in these cells is the first step towards the development of highly specific cancer treatments that can prevent their survival. The study was published in Nature Communications. (Image source: Merino et al., Nature communications 2019)
HPV vaccine leads to decline in two types of HPV linked to cervical cancer
HPV types 16 and 18 – which are responsible for approximately 70% of cervical cancer cases worldwide – are on the decline. As part of the Center for Disease Control’s Human Papillomavirus (HPV) Vaccine Impact Monitoring Project (HPV-IMPACT), researchers examined the incidence of 37 types of HPV in over 10,000 samples from women with grade 2 or 3 cervical intraepithelial neoplasia or adenocarcinoma in situ (CIN2+), both of which are precancerous conditions of the cervix. Overall incidence of CIN2+ declined 21% from 2008 to 2015 (2,344 vs 1,857 cases), and the estimated number of CIN2+ cases attributed to HPV 16/18 infections declined 34% from 2008 to 2014 (1,235 vs 819 cases). This reduction in the number of CIN2+ cases attributed to HPV 16/18 was observed in both vaccinated (55.2%–33.3%) and unvaccinated (51.0%–47.3%) women, suggesting that “herd immunity” may play a role in protecting women from HPV infection. Herd immunity works by stopping the transmission of the bacteria or virus responsible for a certain type of infection. However, this is only possible when a large proportion of a population is protected from a disease by vaccination.
Biotech and Pharma M&A in oncology:
- Investors unsatisfied BMS’ acquisition Celgene: Following last month’s ‘biggest acquisition of the century’-news of Bristol-Meyers Squibb planning to take over Celgene, now the investors have shown an opposing force. Wellington Management – BMS its largest shareholder, holding approximately 8% of its stock – raised its voice and showed their concerns regarding the Celgene transaction. This was rapidly followed by other shareholders, such as Starboard Value who delivered an open letter saying the deal was ‘ill-advised’. According to analyst’s reports, the misgivings are unlikely to prevent the deal.
- Lilly acquires Loxo Oncology: A definitive agreement is signed for the acquisition of all outstanding shares of Loxo Oncology by Eli Lilly, a deal valued $8B in cash. Shares were offered for $235 each, and by buying 26.043.820 shares Lilly owns approximately 84.6% of the shares common stock outstanding. Loxo’s pipeline consists of (amongst others) TRK, BTK and RET inhibitors.
- Merck to acquire Immune design: Merck announced to acquire US based Immune Design, a late-stage immunotherapy company that employs next-generation in vivo approaches with the goal to fight infectious diseases and cancer by vaccine development. Through a subsidiary, Merck acquires Immune Design for $5.85 per share in cash, totaling to an approximate value of $300M total.
The Committee for Medicinal Products for Human Use (CHMP) recommended granting marketing authorization for:
- Lorviqua (lorlatinib, Pfizer) for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC). The orally administered small molecule is an inhibitor of ALK- and ROS1-tyrosinekinase. It is able to cross the blood-brain barrier and therefore is currently being investigated to be used for the treatment of neuroblastoma.
- Pazenir (paclitaxel, Teva) as a generic medicine for the treatment of metastatic breast cancer and NSCLC. The antineoplastic agent targets tubulin and therefore defects the mitotic spindle assembly, chromosome segregation and cell division.
The CHMP extended the therapeutic indication for:
- Lynparza (olaparib, AstraZeneca) as monotherapy for the treatment of adult patients with germline BRCA1/2-mutations, who have HER2 negative locally advanced or metastatic breast cancer. Patients with hormone receptor (HR)-positive breast cancer should also have progressed on or after endocrine therapy, or be considered unsuitable for endocrine therapy. The PARP inhibitor was earlier approved for patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube and primary peritoneal cancer who are in response to platinum-based chemotherapy.
The FDA granted approval for:
- Lonsurf (trifluridine/tipiracil tablets, Taiho Pharmaceutical), a fixed combination of respectively a nucleoside metabolic inhibitor and a thymidine phosphorylase inhibitor for adult patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.
- Keytruda (pembrolizumab, Merck) for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.