Big Moment for Nanotech: Oncology Therapeutics Poised for a Leap

Andrew D. Smith
Published Online: Tuesday, July 2, 2013
nanowire array

This image depicts nanowire arrays synthesized by researchers at Emory/Georgia Tech Center of Cancer Nanotechnology Excellence. The arrays can be used for biosensing, manipulation of cells, and converting mechanical energy into electricity for powering nanodevices.

Illustration courtesy Z.L. Wang, PhD/ NCI Nanotechnology Image Library



Research Advances Are Flowing Along With Investments


The first proof of the cancer-fighting potential of nanotechnology in the United States came in 1995, when the FDA approved the use of an encapsulated liposome to deliver a more heart-friendly form of the chemotherapy doxorubicin.

Yet despite the relative triumphs of doxorubicin liposomal (Doxil), including a sharply lower risk of congestive heart failure in patients with breast cancer and $402 million in 2011 sales, problems ranging from adverse events to manufacturing difficulties have helped slow the development of anticancer therapeutics using nanotechnology.

Until now.

The translation of scientific advances in nanotechnology into cancer therapies, in vitro assays, and imaging tools is poised for takeoff, amid fresh excitement among investors and a mushrooming of findings from leading research institutions.

Key developments include the continuing expansion of the oncology uses for albumin-bound paclitaxel (Abraxane) since the FDA initially approved the drug in 2005 for the treatment of breast cancer after prior chemotherapy. Last October, the agent was approved as a first-line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC); it is now undergoing a priority review as a first-line treatment in combination with gemcitabine for patients with advanced pancreatic cancer.

Another nano-chemotherapy combination, a liposomal formulation of vincristine sulfate called Marqibo, won expedited FDA approval in August 2012 as a third-line treatment for patients with Philadelphia chromosome- negative acute lymphoblastic leukemia (Ph- ALL).

Meanwhile, Nippon Kayaku’s NK105, which delivers paclitaxel in a polymer micelle, has reached a phase III trial in metastatic or recurrent breast cancer (NCT01644890). American biotech companies have advanced other compounds to later-stage clinical trials. And, global pharmaceutical companies have signed deals that could bring more than $1 billion to a tiny Boston-area biotech that recently announced results from its first-ever phase I trial.

Table. Nanotherapeutics Approved for Oncological Applications

Category Agent Description Tumor Type Approval/ Status
Albumin Abraxane (albumin-bound paclitaxel) Microtubule inhibitor that is an albumin-bound form of paclitaxel with a mean particle size of about 130 nm Metastatic breast cancer, locally advanced or metastatic non-small cell lung cancer FDA approval in 2005
Liposomal Doxil
(doxorubicin HCI liposome injection)
Doxorubicin hydrochloride encapsulated in liposomes Recurrent ovarian cancer, AIDS-related Kaposi sarcoma, multiple myeloma FDA approval in 1995; approved in Europe for metastatic breast cancer
DaunoXome
(liposomal daunorubicin)
An aqueous solution of the citrate salt of daunorubicin encapsulated within lipid vesicles Advanced HIV-associated Kaposi sarcoma FDA approval in 1996
Myocet
(liposomal doxorubicin)
Liposome-encapsulated doxorubicincitrate corresponding to 50-mg doxorubicin hydrochloride Metastatic breast cancer FDA fast track designation for HER2- positive metastatic breast cancer; approved in Europe and Canada
Mepact
(muramyl tripeptide phosphatidyl-ethanolamine)
Synthetic derivative of muramyl dipeptide in a liposomal formulation Nonmetastatic, resectable osteosarcoma Approved in Europe; phase III trials in United States
DepoCyt
(liposomal cytarabine)
Injectable suspension of the antimetabolite cytarabine, encapsulated into multivesicular lipid-based particles Lymphomatous meningitis FDA granted accelerated approval in 1999 and full approval in 2007
Marqibo
(liposomal vincristine sulfate)
Vinca alkaloid antimitotic, encapsulated in the aqueous core of sphingomyelin-based liposomes Philadelphia chromosome-negative acute lymphoblastic leukemia FDA approval in 2012
Polymeric Genexol-PM
(Methoxy-PEG-poly[D, L-lactide] taxol)
Copolymer miceller nanoparticleentrapped formulation of paclitaxel Metastatic breast cancer; pancreatic cancer Approved in South Korea for breast cancer; phase II in the United States for pancreatic cancer
Oncaspar
(PEG--L-asparaginase)
L-asparaginase covalently conjugated to monomethoxypolyethylene glycol Acute lymphoblastic leukemia FDA approval in limited setting in 1994, expanded to first line in 2006
Zinostatin stimalamer
(styrene maleic anhydrideneocarzinostatin)
Conjugate protein or copolymer of styrene-maleic acid (SMA) and an antitumor protein neocarzinostatin (NCS)a Primary unresectable hepatocellular carcinoma Approved agent in Japan since 1994
Neulasta
(pegfilgrastim)
Covalent conjugate of recombinant methionyl human G-CSF (filgrastim) and monomethoxypolyethylene glycol Reduce the risk of infection in patients with nonmyeloid malignancies receiving myelosuppressive anticancer therapy associated with febrile neutropenia FDA approval in 2002
Hyperthermia NanoTherm
(superparamagnetic iron oxide nanoparticles)
Nanoparticle-drug conjugates inside tumor heated selectively by a magnetic field, resulting in temperature-dependent release of drug Local ablation in glioblastoma multiforme; prostate and pancreatic cancers Marketing approval in Europe for glioblastoma; phase I/II trials in other tumor types

aIshii H, et al. Jpn J Clin Oncol. 2003;33(11):570-573.

Sources: NCI Alliance for Nanotechnology in Cancer list of oncologic nanotherapeutics, including approval status; descriptions from NCI Drug Dictionary, company websites, and label information for individual agents.

 

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