Dr Nick Plowman, Senior Clinical Oncologist to St Bartholomew’s Hospital and The Hospital for Sick Children, Great Ormond Street, London, provides his view of the current approach to the medical treatment of cancer and future developments.
What is cancer?
Cancer is a process where a clone of normal cells acquires mutations that permit the cells to divide (mitosis) unrelentingly, without the needs and controls that normally preserve equilibriums (homeostasis) within the body. As the cells undergo mitosis, subclones develop, which break off and seed (via the bloodstream, lymphatics etc) to reach other sites in the body where they grow (metastasise). This is true of all cancers - including breast, lung, gut, pancreas, liver, kidney cancers, and lymphoma. Given the metastasising nature of cancer, treatments for advanced cancer cannot entirely rely on “cutting out” the primary tumour; therapies are needed that circulate around the body. Chemotherapy (drugs which inhibit processes that are required for cell division) circulates to achieve these aims. Some of these drugs inhibit DNA replication; others inhibit the metabolic processes needed for mitosis. But, in the main they lack selectivity and therefore cause collateral damage in healthy areas of the body.
Improving chemotherapy for the treatment
Improving the specificity of chemotherapy is a major aspect of the Oncology Clinic at 20 Harley Street. By molecular predictive testing, either looking at beneficial alternations in drug metabolic processes or testing for new mutations in cancer cells that will lead to selectivity for lethality of individual chemotherapy drugs, better targeting and specificity of cancer chemotherapy drugs is achieved. Growing an individual’s cancer cells in vitro or as an in vitro transplant (in mice) is also used to experimentally test for the optimal chemotherapy regime for an individual’s cancer.
Genetic mutations that cause it
Pursuing the goal of specificity in drug treatment, the modern generation of predictive testing specifically probes the genetic mutations that cause a cancer - oncogenes being those that positively stimulate uncontrolled cell divisions, and mutations in suppressor genes – which normally put the brakes on cell division – leading to the same event. If tests show that a particular cancer gene is a major causative contributor to the cancer process, then a drug inhibitor of the “downstream” protein phase effectors of that gene can have profound effects on cancer growth. E.g. EGFR, ALK (Lung cancer) HEV-2 (breast cancer), K-RAS, BRAF, (colorectal, pancreas cancer), BARF, MET, (Melanoma) RET, (thyroid cancer) VHL, M-TOR (kidney cancer), bcl-2, PDGF, (some leukaemia, GIST) etc. This is the new and exciting development in cancer medicine. Sometimes, cancer cells that have depended on one oncogene mutated pathway – then find another pathway for unrelenting cell division and sometimes the combination of different drugs – inhibiting the different pathways may be needed to block cancer growth. E.g. the combination of trastuzumab with pertuzumab in HE-2 positive breast cancer. The Oncology Clinic is well positioned to explore these new drug developments.
Other therapies for the treatment
Some cancers (notably breast cancer and prostate cancers) less significantly uterine cancer, kidney cancer, kidney cancer, meningioma) are hormone dependent and new developments in anti-hormonal therapies have taken interesting turns recently.
Immunotherapy has been appreciated but has been unsuccessful until recently and I include vaccines in this regard. However, recent new developments, exploring new concepts, e.g. ipilimumab in melanoma, anti PDI in lung cancer are opening new avenues of research with some, albeit limited so far, success.